Santiago v. Secretary of Health and Human Services

Opinion

In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS Filed: July 8, 2026

************************* PATRICIA SANTIAGO, * PUBLISHED

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Petitioner, * No. 21-1562V

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v. * Special Master Nora Beth Dorsey

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SECRETARY OF HEALTH * Dismissal; Influenza (“Flu”) Vaccine; AND HUMAN SERVICES, * Idiopathic Thrombocytopenia Purpura * (“ITP”); Severity Requirement; One Day Respondent. * Onset.

*

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Laura Levenberg, Muller Brazil, LLP, Dresher, PA, for Petitioner. Alexa Roggenkamp, U.S. Department of Justice, Washington, DC, for Respondent.

DECISION 1

On July 9, 2021, Patricia Santiago (“Petitioner”) filed a petition for compensation under the National Vaccine Injury Compensation Program (“Vaccine Act” or “the Program”), 42 U.S.C. § 300aa-10 et seq. (2018). 2 Petitioner alleges that she suffered idiopathic thrombocytopenia purpura (“ITP”) as a result of an influenza (“flu”) vaccine she received on October 16, 2019. Petition at Preamble (ECF No. 1). Respondent argued against compensation, stating that “this case is not appropriate for compensation under the terms of the Vaccine Act.” Respondent’s Report (“Resp. Rept.”) at 2 (ECF No. 13). Respondent argued this case should “be

1 Because this Decision contains a reasoned explanation for the action in this case, the undersigned is required to post it on the United States Court of Federal Claims’ website and/or at https://www.govinfo.gov/app/collection/uscourts/national/cofc in accordance with the E- Government Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic Government Services). This means the Decision will be available to anyone with access to the Internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees that the identified material fits within this definition, the undersigned will redact such material from public access. 2 The National Vaccine Injury Compensation Program is set forth in Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended, 42 U.S.C. §§ 300aa-10 to -34 (2018). All citations in this Decision to individual sections of the Vaccine Act are to 42 U.S.C. § 300aa.

dismissed for failure to satisfy [§11(c)(1)(D)],” hereinafter referred to as the severity requirement under the Vaccine Act. Id. Respondent also argued Petitioner failed to “offer reliable evidence to establish a causal relationship” between the flu vaccination and her alleged injury of ITP. Id. at 15.

After carefully analyzing and weighing the evidence presented in this case in accordance with the applicable legal standards, 3 the undersigned finds that Petitioner met the severity requirement under § 11(c)(1)(D) of the Vaccine Act but has failed to provide preponderant evidence that her flu vaccine caused her ITP. Thus, Petitioner has failed to satisfy her burden of proof under Althen v. Secretary of Health & Human Services, 418 F.3d 1274, 1280 (Fed. Cir. 2005). Accordingly, the petition must be dismissed.

I. ISSUES TO BE DECIDED

“The parties stipulate that Petitioner received a[] [flu] vaccination on October 16, 2019.”

Joint Pre-Hearing Submission, filed Jan. 28, 2025, at 1 (ECF No. 81). Petitioner’s diagnosis of ITP 4 is not in dispute. Id.; Petitioner’s Exhibit (“Pet. Ex.”) 10 at 6; Resp. Ex. A at 5.

The parties dispute whether the statutory severity requirement was met. Joint Pre-

Hearing Submission at 2. Specifically, under § 11(c)(1)(D), the parties dispute “whether [P]etitioner has had residual effects of ITP for longer than six months.” Id.

The parties also dispute causation, specifically all three Althen prongs: “(1) whether the [flu] vaccine administered to Petitioner can cause ITP; (2) whether Petitioner’s ITP was caused by receipt of the vaccination at issue, [and] (3) whether the time between Petitioner’s vaccinations and the onset of symptoms would be considered medically acceptable to infer causation-in-fact.” Joint Pre-Hearing Submission at 2.

3 While the undersigned has reviewed all the information filed in this case, only those filings and records that are most relevant will be discussed. See Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally presume that a special master considered the relevant record evidence even though [s]he does not explicitly reference such evidence in h[er] decision.”); Simanski v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 407, 436 (2014) (“[A] Special Master is ‘not required to discuss every piece of evidence or testimony in her decision.’” (citation omitted)), aff’d, 601 F. App’x 982 (Fed. Cir. 2015); Paterek v. Sec’y of Health & Hum. Servs., 527 F. App’x 875, 884 (Fed. Cir. 2013) (“Finding certain information not relevant does not lead to—and likely undermines—the conclusion that it was not considered.”). 4 To avoid confusion, the undersigned will refer to immune thrombocytopenia, idiopathic thrombocytopenia purpura, and immune thrombocytopenia purpura as ITP throughout this Decision. ITP “has been found to be an autoimmune condition, caused by antigens against platelets, resulting in ecchymoses, petechiae, and other bleeding.” Idiopathic Purpura, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=101150 (last visited June 17, 2026).

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II. BACKGROUND

A. Procedural History

Petitioner filed her petition along with medical records 5 and a declaration on July 9, 2021. Petition; Pet. Exs. 1-7. This case was assigned to the undersigned on January 4, 2022. Notice of Reassignment dated Jan. 4, 2022 (ECF No. 9). Respondent filed his Rule 4(c) report on March 7, 2022, arguing compensation should be denied and this case should be dismissed for failure to meet the severity requirement under the Vaccine Act. Resp. Rept. at 2.

The undersigned held a status conference on May 24, 2022 to address the issues raised in Respondent’s Rule 4(c) report. Order dated May 24, 2022 (ECF No. 17). The undersigned explained that she required expert opinion on the question of severity in this case. Id. at 1. From September 2022 to September 2023, Petitioner filed expert reports from Dr. Abhimanyu Ghose and Dr. Omid Akbari and Respondent filed expert reports from Dr. Lisa Baumann Kreuziger and Dr. You-Wen He. Pet. Exs. 10, 40, 72; Resp. Exs. A, C-D.

Thereafter, pursuant to the parties’ request, the undersigned held a Rule 5 Conference on November 28, 2023. Rule 5 Order dated Nov. 28, 2023 (ECF No. 41). The undersigned indicated that she was unable to provide her preliminary opinions and findings in this case. Id. at 2. Because there was litigative risk for both parties, the undersigned recommended informal settlement discussions. Id. at 2-3.

Respondent indicated he was not interested in settlement, and the matter was scheduled for an entitlement hearing in March 2025. Order dated Feb. 20, 2024 (ECF No. 47); Prehearing Order dated Mar. 22, 2024 (ECF No. 50). Over the next year, prior to the entitlement hearing, additional expert reports from Dr. Akbari and Dr. He were filed. Pet. Exs. 88, 115; Resp. Ex. F.

An entitlement hearing was held from March 4 to March 6, 2025. Order dated Mar. 6, 2025 (ECF No. 102). Petitioner, Dr. Ghose, Dr. Akbari, Dr. Baumann, and Dr. He testified at the hearing. Transcript (“Tr.”) 3, 149, 272. Thereafter, Petitioner requested post-hearing briefing. Order dated Mar. 13, 2025 (ECF No. 105).

Petitioner filed her post-hearing brief on July 10, 2025. Pet. Post-Hearing Brief (“Br.”), filed July 10, 2025 (ECF No. 114). On August 8, 2025, Respondent filed a status report indicating that he “does not intend to file a post-hearing brief.” Resp. Status Rept., filed Aug. 6, 2025 (ECF No. 115).

This matter is now ripe for adjudication.

5 Medical records were filed throughout litigation.

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B. Factual History

1. Medical History 6

a. Pre-Vaccination Medical History

On March 7, 2016, Petitioner saw Dr. Shana Weiss, her primary care physician (“PCP”), for an annual physical examination. Pet. Ex. 2 at 5. Petitioner’s physical examination was normal, and her platelet count was 369 K/uL (reference range: 140-400 K/uL). Id. at 5-6.

On September 5, 2017, Petitioner saw Dr. Sarah Peterson, allergist, to establish care as a new patient. Pet. Ex. 3 at 39. She reported having nasal allergies for “years” as well as adultonset asthma. Id. She reported that full tabs of antihistamines made her drowsy so she was taking half-tabs of Zyrtec. Id. An examination found Petitioner was allergic to dogs, cats, feather mix, trees, grass, Bermuda grass, and mold. Id. at 40.

On March 9, 2018, Petitioner saw Dr. Peterson for an “increase in asthma symptoms in recent weeks/months.” Pet. Ex. 3 at 20. Petitioner noted that antihistamines would lead to “significant grogginess” where she would feel “drunk.” Id. She was applying for FMLA, as the medications would not allow her to drive to work safely. Id. She also stated that she had experienced drowsiness in response to Singulair in the past. Id. at 22. Dr. Peterson filled out Petitioner’s FMLA paperwork, planned to repeat labs, and prescribed Petitioner one-half tab Zyrtec daily. Id.

On October 16, 2019, Petitioner underwent a pre-employment screening determination at Saint Anthony Hospital. Pet. Ex. 1 at 6-22. She was certified as able to perform essential functions of the job as per the job description. Id. at 10. Her physical was normal. Id. at 11-19. She noted that she had suffered from allergic reactions that interfered with her breathing along with asthma in the past but indicated that she did not currently suffer from breathing problems. Id. at 16-17. She was using an albuterol inhaler for breathing problems. Id. at 11, 17. The remainder of Petitioner’s pre-employment screening was normal. Id.

b. Post-Vaccination Medical History

On October 16, 2019, at 57 years old, Petitioner received a quadrivalent flu vaccination (Flucelvax) as part of her medical clearance as a new employee (registered nurse) at Saint Anthony’s Hospital. Pet. Ex. 1 at 8-9, 26.

On October 17, 2019, Petitioner saw Dr. Peterson for a follow up of her allergic rhinitis, asthma, and hives. Pet. Ex. 2 at 91. Petitioner reported receiving her flu shot the day prior, and “about an hour later when she got home she [] [felt] shaky and cold. She then developed

6 This summary of medical records is largely taken from the parties’ prehearing briefs, as the undersigned finds the parties provided an accurate representation of the records. See Pet. Mot. at 2-3; Resp. Response at 3-9. The undersigned has made edits, deleted less relevant entries, and has included additional information.

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petechiae[7] at the site of the injection as well as a few on her opposite arm, on her face, and inside her mouth.” Id. Petitioner also reported “[one] episode of dyspnea [that] morning, [which] resolv[ed] with albuterol.” Id. On examination, Petitioner had a “few petechiae in buccal membrane and [one] on tongue.” Id. at 92. Petitioner also had one petechia on her right deltoid, one on her nose, and a few scattered on her left forearm. Id. Her heart was “mildly [tachycardic].” Id. Dr. Peterson diagnosed Petitioner with a “[r]eaction to [the] flu vaccine” and recommended that she undergo lab testing, start a Medrol Dose pack (low-dose steroids), and return if her symptoms worsened or failed to improve. Id.; Pet. Ex. 3 at 9. A complete blood count (“CBC”) performed on October 17, 2019 was abnormal, showing a platelet count of 5 K/uL (reference range: 131-340 K/uL). Pet. Ex. 3 at 2.

The following day, around 10:00 AM on Friday, October 18, 2019, Petitioner presented to the emergency department (“ED”) at Northwestern Medical Center at the advice of her allergist. Pet. Ex. 4 at 65-66. She was contacted regarding her platelet count of 5 and instructed to present to the ED. Id. at 66. She was seen by emergency medicine physician Steven W. Hodges, M.D. around 11:30 AM. Id. at 65. Petitioner described being in her “usual state of health” when she received a flu vaccination two days earlier, and “within ten minutes of the injection, she was tachycardiac. [Petitioner] later went home and noted muscle aches and chills on the drive home, and when she arrived home, her husband noted significant shivering and rigors that continued for about one hour.” Id. at 65-66. Petitioner reported having a fever of 103º Fahrenheit and petechiae around the area of injection, her face, and in her mouth. Id. at 66. When she presented to her allergist the day prior, she had “more isolated petechiae on arm, chest, and face and was prescribed a Medrol dose pack and labs were drawn.” Id. Petitioner had taken two doses of the Medrol dose pack and has “noticed a decrease in the darkness of petechial lesions.” Id.

Repeat labs were ordered in the ED. Pet. Ex. 4 at 68. Petitioner’s platelets were low at 39 K/uL (reference range: 140-390 K/uL). Id. Her C-reactive protein (“CRP”) level was elevated at 2.4 (reference range: 0.0-0.5 mg/dL) and her erythrocyte sedimentation rate (“ESR”) was also elevated at 100 (reference range: 0-30 mm/hour). Id. at 69, 76. A peripheral blood smear taken at approximately 1:00 PM that day confirmed thrombocytopenia 8 and no platelet clumping was observed. Id. at 76. Hematology and oncology were consulted, Petitioner was given steroids, and repeat labs were recommended. Id. Repeat labs showed an increase in Petitioner’s platelet count to 50 K/uL. Id. at 76, 113. Petitioner was discharged from the ED with instructions to continue taking prednisone for four days and to follow up with hematology on Monday (October 21, 2019). Id. at 76.

7 Petechia is “a pinpoint, nonraised, perfectly round, purplish red spot caused by intradermal or submucous hemorrhage.” Petechia, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=38200 (last visited June 17, 2026). 8 Thrombocytopenia refers to a decrease in platelets. Thrombocytopenia, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=49875 (last visited June 17, 2026).

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A report to Vaccine Adverse Event Report System (“VAERS”) was submitted on October 18 on Petitioner’s behalf by Phyllis Murillo, who appears to work at Petitioner’s employer, Saint Anthony’s Hospital. Pet. Ex. 1 at 26.

On October 23, 2019, Petitioner presented to hematologist Daniel Dammrich, M.D., for an initial appointment. Pet. Ex. 4 at 61. Petitioner reported that she received a “flu shot last week and immediately after develop[ed] shaking chills. She went on to develop petechiae on her face and hands and most prominently in her buccal mucosa.” Id. She also reported her visits to her allergist and the ED and that she completed her steroids that day (October 23). Id. at 61-62. Dr. Dammrich ordered labs that day, October 23, which showed Petitioner’s platelets had “normaliz[ed]” to 323 K/uL (reference range: 140-390 K/uL). Id. at 57, 62. Dr. Dammrich diagnosed Petitioner with ITP that was “possibly a reaction to flu shot as it happened immediately after.” Id. at 63. He further opined that Petitioner’s ITP was “[l]ikely precipitated by vaccination given the timing of onset.” Id. He noted that Petitioner had a “[g]reat response to steroids.” Id. Petitioner was prescribed a three-day regimen of dexamethasone (a steroid) and Dr. Dammrich planned to “recheck [her platelet count] in [one] month since platelets have already normalized.” Id.

On November 25, 2019, Petitioner followed up with Dr. Dammrich. Pet. Ex. 4 at 41.

Petitioner’s platelet count was 391 K/uL (reference range: 140-390 K/uL). Id. at 33. Petitioner complained of fatigue, occasional shortness of breath, and possible tachycardia. Id. at 42. Dr. Dammrich ordered a thyroid stimulating hormone (“TSH”) test and an EKG and noted that if those tests were unremarkable, then Petitioner would follow up with her PCP the next week. 9 Id. at 43. Petitioner was also instructed to follow up with Dr. Dammrich in six months. Id.

On December 28, 2019, Petitioner saw Dr. Weiss, her PCP, for a possible ear infection.

Pet. Ex. 2 at 27. The visit notes document Petitioner’s ITP diagnosis in October 2019. Id. No report of fatigue was documented. Id. at 27-28.

Petitioner saw nurse practitioner Ellen Verlen, at her PCP’s office, on April 17, 2020 via telehealth for a possible Covid-19 infection. Pet. Ex. 2 at 30. Petitioner stated that she was working as a nurse and that one of her coworkers had died that week. Id. She further stated that she had been sleeping poorly as her sister had died from Covid the previous week. Id. Petitioner’s ITP, or any related sequela, was not mentioned. Id. at 30-31.

On May 20, 2020, Petitioner saw Dr. Dammrich for follow-up via telemedicine. Pet. Ex.

4 at 28. Fatigue was not mentioned or documented at this visit. Id. at 28-30. Dr. Dammrich ordered labs, which returned on May 26, 2020 and showed a platelet count of 375 K/uL (reference range: 140-390 K/uL). Id. at 16-17, 31.

On May 27, 2020, Petitioner emailed counsel and stated that her platelets were above 370,000 K/uL and that she was “still tired at times but otherwise [she was] doing ok.” Pet. Ex. 6 at 1. She also noted that her hematologist “want[ed] [her] to continue to follow[] up in [six] months due to possibilities of [her] ITP rebounding.” Id.

9 Her TSH was normal at 1.75 (reference range: 0.40-4.00 uIU/ML). Pet. Ex. 4 at 37.

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Petitioner’s platelet count remained normal for the remainder of 2020, with no reports of related bruising, bleeding, or fatigue. See Pet. Ex. 2 at 34-35, 39-40 (reporting insomnia but “thinks it might [be] related to comfort with new knee [post-surgery]” and denying fatigue under review of systems), 80; Pet. Ex. 4 at 8-10, 13-14 (“Her platelet count has remained normal as of end of May and she has no symptoms to suggest that it has fallen.”); Pet. Ex. 8 at 32; Pet. Ex. 9 at 54.

Petitioner called her hematologist’s office on October 30, 2020, requesting a written statement for her employer that “she cannot take flu shots.” Pet. Ex. 5 at 8. Registered nurse Abigail I. Vollmer indicated that a letter was faxed to Petitioner as requested. 10 Id.

The medical records do not show that Petitioner had any recurrence of her ITP.

No additional relevant medical records were provided.

2. Petitioner’s Declaration and Hearing Testimony

Petitioner has worked as a registered nurse since 1990. Tr. 153-54.

She received the subject flu vaccination on October 16, 2019, in the afternoon. Tr. 157, 176-77. Following her vaccination, she had an hour drive home. Tr. 158. On her drive home, she started feeling “really bad” about 20 minutes into the drive, or about 30 minutes after vaccination, which she described as uneasiness and shortness of breath. Tr. 158, 160-61, 177-80. When she got home, she had chills, shakiness, and body cramps. Tr. 158-61, 179.

When she woke the next morning, October 17, around 8:00 A.M. or 9:00 A.M., she “didn’t feel bad,” but saw petechiae/“blood blisters” on her face, chest, and legs and inside her mouth. Tr. 159, 162, 180-82. That afternoon, she presented to her allergist, Dr. Peterson. Tr. 158, 162, 182-83. Blood work was ordered and Petitioner was started on a Medrol dose pack (low-dose steroids). Tr. 183-84.

The following day, October 18, she drove to the ER on instruction of her allergist due to her platelet level of five. 11 Tr. 164. She was treated with dexamethasone, a high-dose steroid, and she quickly started to improve. Tr. 164-65. She was discharged that day 12 and instructed to continue with steroids and to see a hematologist. Tr. 165-68, 187-88.

10 It does not appear that a copy of the letter was filed.

11 In her declaration, Petitioner averred her symptoms began “[w]ithin forty-eight (48) hours of [flu] vaccination.” Pet. Ex. 7 at ¶ 3. 12 Petitioner explained that the ER physicians wanted to admit her, but she “beg[ged]” to go home as she had already been there for hours. Tr. 185. She indicated she would return if needed, referring to her knowledge as a registered nurse. Id. She further testified that she, like other nurses, “are probably some of the worst patients.” Id.

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She then began care with hematologist Dr. Dammrich. Tr. 165-68. Her platelets were considered normal at her first visit with Dr. Dammrich in October. Tr. 188-89. She continued to follow up with Dr. Dammrich. Tr. 190. In November 2019, her platelets remained normal despite her continuing fatigue. Tr. 191, 198.

She testified that she consistently complained of fatigue at her visits with Dr. Dammrich.

Tr. 165-66, 170. Petitioner averred she reported fatigue at her visit with Dr. Dammrich on May 20, 2020, despite no documentation of such complaint in his record. Pet. Ex. 7 at ¶ 6; see also Tr. 170. She “always felt like his only concern was what [her] platelet count reading was at each visit.” Pet. Ex. 7 at ¶ 6.

As of July 8, 2021, the date on which Petitioner’s declaration was executed, she continued to “feel overly fatigued at times.” Pet. Ex. 7 at ¶ 7; see also Tr. 168 (testifying that her fatigue “probably” lasted “a year or more” and would fluctuate). At the entitlement hearing in March 2025, she testified that the fatigue would affect her daily life. Tr. 171. She has been taking vitamins and supplements to counteract her fatigue. Tr. 198. Petitioner was unable to work for two weeks after her diagnosis of ITP, but she was able to return to work full-time thereafter. Tr. 170-71.

She testified that she had received flu vaccines in prior years and never experienced these symptoms following vaccination. Tr. 157-58, 161. She reported experiencing fatigue when she was sick with the flu or Covid as well as during the Covid pandemic during which time she was working as a nurse. Tr. 167-68, 202-05. She also reported grogginess on a half-tab of Zyrtec, which she has taken daily since approximately 2017. Tr. 199-201.

C. Expert Reports 13

1. Petitioner’s Expert, Dr. Abhimanyu Ghose 14

a. Background and Qualifications

Dr. Ghose is board certified in internal medicine and hematology and oncology. Pet. Ex.

10 at 1; Pet. Ex. 157 at 9. After receiving his M.B.B.S. in 2007 from Nilratan Sircar Medical College in India, he worked in India as a physician before beginning an internal medicine residency in 2009 at the University of Toledo, Ohio. Pet. Ex. 10 at 1-2; Pet. Ex. 157 at 1-2. He then completed a fellowship in hematology-oncology in 2015 at the University of Cincinnati in Ohio. Pet. Ex. 10 at 1; Pet. Ex. 157 at 1. He currently works at Arizona Center for Cancer Care/ Honorhealth Virginia G. Piper Cancer Care Network and is a clinical assistant professor of

13 For the sake of brevity and clarity, the undersigned does not summarize all of the experts’ opinions or testimony and attempts to limit this Decision to the most material and relevant opinions. 14 Dr. Ghose provided two expert reports and testified at the entitlement hearing. Pet. Exs. 10, 72; Tr. 3.

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Internal Medicine, Hematology Oncology at A.T. Still University School of Osteopathic Medicine and Grand Canyon University in Arizona. Pet. Ex. 10 at 1; Pet. Ex. 157 at 1. He previously worked Arizona Oncology/US Oncology Network as a principal investigator for multiple clinical trials. Pet. Ex. 10 at 1; Pet. Ex. 157 at 1. Dr. Ghose has been an expert witness on more than 20 cases including Vaccine Program cases. Pet. Ex. 157 at 1. He is a member of and has served on various societies and boards, and he has authored or co-authored over 30 publications, abstracts, and presentations focused on hematology and oncology. Id. at 4-9; Pet. Ex. 10 at 1; Tr. 8.

Dr. Ghose is “an expert in hematological disorders including [ITP].” Pet. Ex. 10 at 2.

Since 2015, he has worked in private practice treating hematological patients and he “sees patients with ITP on a regular basis.” Pet. Ex. 10 at 2; see also Tr. 7. Dr. Ghose was offered and admitted as an expert in hematology without objection. Tr. 9. Dr. Ghose was not admitted as an expert in immunology. Tr. 74-75.

b. Opinion

i. Severity Requirement

Dr. Ghose opined Petitioner “more likely than not” met the six-month severity requirement because she continued to experience fatigue as a result of her ITP despite her normalized platelet counts. Tr. 11, 19-20; Pet. Ex. 10 at 3-4.

He explained that ITP is an immune-mediated disorder that leads to the destruction of platelets. Tr. 11-12. Patients with ITP “present with bleeding manifestations” including bruising, petechiae, and bleeding. Tr. 12-13. Dr. Ghose explained that “ITP is not only a disease of platelets but also a plethora of residual symptoms,” including fatigue, which “can affect [patients’] daily activities” as well as their work and social life. Pet. Ex. 10 at 7; Tr. 13; see also Pet. Ex. 10 at 5 (noting fatigue as a “consequence[] of ITP”); Pet. Ex. 72 at 3 (“Tiredness or fatigue is a known debilitating symptom of ITP.”).

He cited various articles to support fatigue as a residual sequela of ITP. McMillian et 15 al., for example, evaluated health-related quality of life in 73 adults with chronic ITP and found the health-related quality of life of adult ITP patients is “significantly worse” than that of the general U.S. population. Pet. Ex. 12 at 1; see also Pet. Ex. 10 at 4-5. The authors acknowledged that they were unable to examine whether a correlation between platelet counts and health- related quality of life scores existed. Pet. Ex. 12 at 4.

15 Robert McMillian et al., Self-Reported Health-Related Quality of Life in Adults with Chronic Immune Thrombocytopenic Purpura, 83 Am. J. Hematol. 150 (2008).

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Dr. Ghose also cited Mathias et al., 16 who showed ITP “affects many other facets of life,”

including fatigue. Tr. 17-19 (citing Pet. Ex. 148); see also Pet. Ex. 10 at 6. In three focus groups of 23 total ITP patients, fatigue was reported as well as the effects of fatigue on daily activities and work. Pet. Ex. 148 at 5, 6 tbl.1. In two of the focus groups, totaling 15 participants, fatigue was reported by 14 of the 15 participants (93%). Id. at 5, 7, 7 tbl. 2. One of those participants characterized fatigue as the “number one [issue].” Id. at 8, 9 tbl. 3. Other patients reported their daily activities were limited due to fatigue. Id. at 10.

Hill and Newland 17 examined fatigue in ITP patients. Pet. Ex. 63 at 1. They indicated “[f]atigue is an important aspect of health-related quality of life from the patient perspective” and “a significant number of both adults and children with [ITP] suffer from fatigue.” Id. Hill and Newland summarized previous studies that reported fatigue in patients with ITP, including Mathias et al. Id. at 2. The authors also noted “[i]t is less clear whether fatigue is associated with disease severity as measured by the platelet count” and summarized studies that have found fatigue did and did not correlate to platelet count. Id.

Grace et al. 18 also studied fatigue in ITP patients, though specifically children and adolescents with ITP. Pet. Ex. 153 at 1. The authors found “[c]hildren and adolescents with ITP reported a similarly high level of fatigue [at study entry] with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate-to-severe fatigue.” Id. at 1, 3. They further noted fatigue scores, which were measured at study entry (baseline), one month after treatment began, and 12 months after treatment began, “did not correlate with bleeding symptoms, platelet count, or platelet response to treatment.” Id. at 1, 4 tbl. II, 5-6 (“Fatigue scores [] did not differ based on platelet response to treatment at [one] or 12 months. In addition, fatigue scores did not correlate with the most recent platelet counts at baseline, [one] month, or 12 months after starting treatment.” (internal citations and data omitted)).

Zhang et al. 19 focused on changes in fatigue among Chinese ITP adults. Pet. Ex. 154 at 2. Zhang et al., like Hill and Newland and Grace et al., examined whether there was a correlation between fatigue and platelet count. Id. at 8. They concluded that in their study with 175 patients, there was “[n]o relationship [] found between platelet count and fatigue . . . , which

16 Susan D. Mathias et al., Impact of Chronic Immune Thrombocytopenic Purpura (ITP) on Health-Related Quality of Life: A Conceptual Model Starting with the Patient Perspective, 6 Health Qual. Life Outcomes 1 (2008). 17 Quentin A. Hill & Adrian C. Newland, Fatigue in Immune Thrombocytopenia, 170 Br. J. Haematol. 141 (2015). 18 Rachael F. Grace et al., Fatigue in Children and Adolescents with Immune Thrombocytopenia, 191 Br. J. Haematol. 98 (2020). Grace et al. cited a study that examined fatigue in 34 adults with ITP and determined fatigue was not related to disease severity or affected by therapy. Pet. Ex. 153 at 2. This study was not filed in this case. 19 Wenhui Zhang et al., Fatigue and Health-Related Quality of Life in Patients with Immune Thrombocytopenia: A Longitudinal Assessment in China, 16 Expert Rev. Hematol. 1125 (2023).

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was consistent with previous studies that showed that platelet counts were not associated with fatigue in ITP patients.” Id. Zhang et al. also determined that their patients’ fatigue improved at discharge but worsened at three months after discharge. Id. at 1, 9.

Cooper et al. 20 also examined the effects of ITP on quality of life and concluded “[p]hysicians should be aware not only of platelet counts and bleeding but also the multidimensional impact of ITP on patients’ lives as an integral component of disease management.” Pet. Ex. 152 at 1. They documented patients reported their “ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%).” Id. Fifty percent of patients reported fatigue, while 38% of physicians reported their patients felt fatigued, with 46% of these patients at a “high level of fatigue.” Id. at 3. Viana et al. 21 similarly found half of their patients (49.9%) were experiencing fatigue. Pet. Ex. 151 at 7, 8 tbl. 3.

Although some of these studies focused on patients with chronic ITP, and Petitioner had acute ITP, Dr. Ghose opined these studies are still relevant and apply to Petitioner as the distinction of chronic versus acute is based on the length of time platelets are low. Tr. 50. Moreover, these studies, according to Dr. Ghose, “haven’t actually said that fatigue happens only in chronic ITP patients.” Tr. 57.

Despite the fact that Petitioner’s platelets normalized in October 2019, she continued to experience fatigue, which Dr. Ghose opined was a residual symptom of her ITP. Tr. 11, 39 (testifying that because of her continued symptoms of fatigue, Petitioner had not fully recovered clinically). Dr. Ghose explained that patients can continue to experience fatigue even when platelets have normalized. Tr. 19, 42. For support, he cited to Petitioner’s affidavit and email to counsel, which reported continued complaints of fatigue through May 2020, despite a normal platelet count. Pet. Ex. 10 at 4 (citing Pet. Ex. 4 at 20; Pet. Ex. 6 at 1; Pet. Ex. 7 at 1). Hill and Newland noted studies that have found fatigue did not correlate to platelet count. Pet. Ex. 63 at 2. In Grace et al., the authors determined fatigue scores “did not correlate with bleeding symptoms, platelet count, or platelet response to treatment.” Pet. Ex. 153 at 1. And Zhang et al. found “[n]o relationship . . . between platelet count and fatigue.” Pet. Ex. 154 at 8.

With regard to Petitioner’s complaints of sleeping poorly in April 2020 due to the Covid pandemic and her sister’s death, Dr. Ghose testified that he cannot say whether her fatigue would be due to her sleeping poorly or her ITP at this time. Tr. 61. He opined, “more likely than not,” Petitioner’s complaints of fatigue to Dr. Dammrich in November 2019 as well as in May 2020, as also evidenced by Petitioner’s email and testimony, was a residual symptom of her ITP. Tr. 19-20; Pet. Ex. 10 at 3-4.

20 Nicola Cooper, Immune Thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on Health-Related Quality of Life, 96 Am. J. Hematol. 199 (2021). 21 Ricardo Viana et al., Psychometric Evaluation of ITP Life Quality Index (ILQI) in a Global Survey of Patients with Immune Thrombocytopenia, 38 Adv. Ther. 5791 (2021).

12

As to any lack of documentation of fatigue in Petitioner’s medical records, Dr. Ghose explained that fatigue “[is] not measured objectively in routine visits by physicians and [is] often missed.” Pet. Ex. 72 at 3; see also Pet. Ex. 148 at 11 (“[D]espite [] finding that over 90% of the patients in [two] focus groups mentioned fatigue, currently fatigue is not sufficiently often considered by clinicians who manage persons with ITP. In fact, fatigue is seldom recorded as an adverse event in clinical trials of ITP patients.”). He explained that hematologists focus on measuring patient’s platelet counts as it is an objective measurement that can be corrected. Tr. 20-21; see also Tr. 23 (noting platelet counts are “what [hematologists] go by”); Pet. Ex. 12 at 2 (“Physicians caring for ITP patients tend to focus on the platelet count and may fail to appreciate the magnitude of the effect of ITP and its treatment on their patients’ quality of life.”); Pet. Ex. 148 at 7 (“Platelet counts, with or without the presence of any signs or symptoms, are often the only determinant of treatment decisions and are also used to establish whether the patient has responded to treatment and whether the response is considered complete, partial, or minimal.”). Fatigue, on the other hand, “is not easy to correct” and thus, “the focus is on whether the platelets have normalized.” Tr. 21; see also Tr. 55-56; Pet. Ex. 151 at 3 (“The International Consensus Report has mentioned that severe fatigue is the most difficult ITP symptom to treat, experienced by 39–59% of adult patients, yet it is under-recognized by healthcare practitioners. Further, physicians primarily focus on platelet count whereas fatigue and [other] symptoms . . . are often the more primary concerns of patients.”); Pet. Ex. 148 at 11 (“[P]latelet counts, with or without the presence of symptoms, can dictate whether to treat ITP.”). Moreover, certain documentations in medical records are not often updated and therefore “they don’t completely reflect what the patient may be saying or may not be saying. So a lot of times physicians focus just on platelets[] [and] they don’t update the notes.” Tr. 64.

ii. Althen Prong One

Dr. Ghose opined that the flu vaccine can cause ITP via “[m]olecular mimicry to the proteins in the vaccine with that of platelets, causing the body to generate antibodies against it.” Pet. Ex. 10 at 4, 7. In other words, “antibodies against . . . vaccine antigens cross-react with normal platelet antigens,” which “causes a drop in platelets as the platelets are falsely recognized as foreign to the body.” Id. at 4. He opined molecular mimicry was “the most plausible explanation.” 22 Id. at 7; see also Pet. Ex. 17 at 1-2 (stating molecular mimicry is the “most likely” theory by which vaccines induce ITP). 23

22 Dr. Ghose also noted another mechanism in his first report: “an immune alteration where there is loss of self tolerance and body’s development of self-reactive antibodies are promoted like in hematological malignancies like [Chronic Lymphocytic Leukemia] and autoimmune diseases.” Pet. Ex. 10 at 4. Dr. Ghose did not discuss this theory further, and thus, the undersigned finds it was not developed and will not be discused. In his second expert report, Dr. Ghose adopted Dr. Akbari’s inflammasome and hypersensitivity theories. Pet. Ex. 72 at 2. Because these theories will be discussed in more detail below in Dr. Akbari’s expert section, the undersigned does not discuss these opinions here. 23 Carlo Perricone et al., Immune Thrombocytopenic Purpura (ITP) Associated with Vaccinations: A Review of Reported Cases, 60 Immunologic Rsch. 226 (2014). This was also filed as Pet. Ex. 107.

13

In Perricone et al., the authors offered molecular mimicry as the process by which “[a]ntibodies responsible for the clearance of virus antigens may cross-react with antigens naturally present on platelets.” Pet. Ex. 17 at 2. The authors hypothesized that with the flu vaccine, “the target of molecular mimicry probably involves hemagglutinin” (“HA”), “the main antigen in [flu] vaccines.” Id. at 4. According to Perricone et al., HA has been shown to “bind[] to platelets, through receptors bearing a terminal N-acetyl neuraminic acid group displayed on their surface. Consequently, the membrane-bound HA can be recognized by the anti-HA antibodies, triggering activation of the complement cascade which induces platelet lysis and thrombocytopenia.” Id. While molecular mimicry is the current prevailing theory, the authors acknowledged that the pathogenic mechanisms of ITP have not been fully explained. Id. at 2.

Dr. Ghose opined infections and vaccinations, including the flu infection and vaccination, have been associated with ITP in the literature. 24 Pet. Ex. 10 at 4-5; Pet. Ex. 72 at 1; Tr. 12, 16; see, e.g., Pet. Ex. 16 at 3-12 (describing infectious agents and vaccinations that have been associated with ITP); 25 Pet. Ex. 17 at 2-7 (same). Rinaldi et al. explained “[t]he vaccinesautoimmunity interplay is very similar to the established association between infections and autoimmunity. Infectious agents can cause or trigger autoimmunity through several mechanisms such as molecular mimicry . . . . .” Pet. Ex. 16 at 8; see also Pet. Ex. 17 at 2.

24 The undersigned does not discuss literature that does not address the flu vaccine or flu infection for the sake of brevity and due to lack of relevance. See Pet. Ex. 14 (E. Miller et al., Idiopathic Thrombocytopenic Purpura and MMR Vaccine, 84 Arch. Dis. Child. 227 (2001)) (also filed as Pet. Ex. 27); Pet. Ex. 22 (Laura J. Sauvé & David Scheifele, Do Childhood Vaccines Cause Thrombocytopenia?, 14 Paediatr. & Child Health 31 (2009)); Pet. Ex. 24 (Eric K. France et al., Risk of Immune Thrombocytopenic Purpura After Measles-Mumps-Rubella Immunization in Children, 121 Pediatrics e687 (2008)); Pet. Ex. 25 (Corri Black et al., MMR Vaccine and Idiopathic Thrombocytopaenic Purpura, 55 Brit. J. Clin. Pharmacol. 107 (2003)); Pet. Ex. 26 (Annie P. Jonville-Bera et al., Thrombocytopenic Purpura After Measles, Mumps and Rubella Vaccination: A Retrospective Survey by the French Regional Pharmacovigilance Centres and Pasteur-Merieux Serums et Vaccins, 15 Pediatr. Infect. Dis. J. 44 (1996)); Pet. Ex. 28 (Laura J. Sauvé et al., Postvaccination Thrombocytopenia in Canada, 29 Pediatr. Infect. Dis. J. 559 (2010)) (also filed as Resp. Ex. A10); Pet. Ex. 29 (Judy Beeler et al., Thrombocytopenia After Immunization with Measles Vaccines: Review of the Vaccine Adverse Events Reporting System (1990 to 1994), 15 Pedistr. Infect. Dis. J. 88 (1996)) (also filed as Pet. Ex. 77); Pet. Ex. 30 (Vasiliki Vlacha et al., Recurrent Thrombocytopenic Purpura After Repeated Measles- Mumps-Rubella Vaccination, 97 Pediatrics 738 (1996)); Pet. Ex. 34 (Eun-Ju Lee et al., Thrombocytopenia Following Pfizer and Moderna SARS-CoV-2 Vaccination, 96 Am. J. Hematol. 534 (2021)) (also filed as Pet. Ex. 84); Pet. Ex. 73 (Anna C. Bibby et al., Is MMR Immunisation Safe in Chronic Idiopathic Thrombocytopenic Purpura?, 93 Arch. Dis. Child. 354 (2008)). 25 M. Rinaldi et al., Immune Thrombocytopaenic Purpura: An Autoimmune Cross-Link Between Infections and Vaccines, 23 Lupus 554 (2014).

14

Isai et al. 26 reviewed a database of reports of suspected adverse reactions in the European Union from October 2009 to December 2010 for adjuvanted and non-adjuvanted pandemic flu A/H1N1 vaccines. Pet. Ex. 79 at 1. The data included reports of autoimmune adverse reactions where an adjuvanted or unadjuvanted A/H1N1 vaccine was reported as suspect, interacting, or concomitant. Id. at 2. The authors reported that ITP was the third most common autoimmune condition following flu vaccination. Id. at 3 tbl.2.

Perricone et al. summarized articles describing an association between the flu vaccine and ITP. Pet. Ex. 17 at 4, 5 tbl.1. For example, “Garbe et al. found that [flu] vaccine has a ‘probable’ causality to induce ITP.” Id. at 4 (citing Pet. Ex. 53 at 1-2, 9). 27 Garbe et al. was a large case-control surveillance study that used data from Berlin hospitals on adults from 2000 to 2009. Pet. Ex. 53 at 1. Ninety of the 169 total cases of ITP were determined to be drug-related, and these included vaccines. Id. at 1-2, 9. Three of the cases were related to the flu vaccine. Id. Vaccine causality was determined to be “probable” using the World Health Organization (“WHO”) standardized causality assessment tool. 28 Id. at 9. The “[flu] vaccination was associated with a statistically significant [four]-fold risk.” Id.

Jadavji et al. 29 reported on data obtained from 12 pediatric centers in Canada from 1992 to 2001. Pet. Ex. 23 at 1. The authors identified 61 patients who had decreased platelet counts within 30 days of vaccination. Id. Two of the patients developed thrombocytopenia after the flu vaccine, at 10 and 14 days post-vaccination. 30 Id. at 2, 2 tbl. 1.

26 Alina Isai et al., Autoimmune Disorders After Immunisation with Influenza A/H1N1 Vaccines with and Without Adjuvant: EudraVigilance Data and Literature Review, 30 Vaccine 7123 (2012). 27 Edeltraut Garbe et al., Drug-Induced Immune Thrombocytopaenia: Results from the Berlin Case-Control Surveillance Study, 68 Eur. J. Clin. Pharmacol. 821 (2012). This was also filed as Pet. Exs. 104, 147. 28 The WHO assessment of causality includes the categories certain, probable, possible, unlikely, unclassified, and unclassifiable. Pet. Ex. 53 at 3. “A drug reaction was evaluated as ‘probable’ when the ITP occurred with a reasonable time [after] administration[,] . . . was unlikely to be attributed to other causes, and a positive dechallenge reaction was observed on drug withdrawal.” Id. at 3-4. 29 Taj Jadavji et al., Thrombocytopenia After Immunization of Canadian Children, 1992 to 2001, 22 Pediatr. Infect. Dis. J. 119 (2003). This was also filed as Pet. Ex. 35. 30 Of note, the authors noted a limitation of the study, in that the majority of patients with post- vaccination thrombocytopenia also had a viral infection or exposure to medication that could suggest an alternate cause of the illness. Pet. Ex. 23 at 3.

15

For further support, he cited numerous case reports of ITP post-flu vaccination. Tishler 31 et al. reported on a 68-year-old patient who developed severe thrombocytopenia 14 days following receipt of a flu vaccine. Pet. Ex. 18 at 1. Regarding causation, the authors explained that “[t]he most popular hypothetical mechanism for the triggering of autoimmunity by an infectious agent is that of molecular mimicry.” Id.

Ohta and Sano 32 described a case of acute onset ITP in an 88-year-old male four days after receiving a flu vaccination. Pet. Ex. 20 at 1. He was diagnosed with “[flu] vaccine-induced severe ITP,” and the authors noted his case “suggest[ed] that [flu] vaccines can be associated with ITP.” Id. at 3. The authors did not discuss any mechanisms by which the flu vaccine can cause ITP.

Nagasaki et al. 33 reported ITP four to five weeks following flu vaccination in three elderly patients, ages 75, 81, and 87. Pet. Ex. 21 at 1-2. The authors concluded that “[v]accineassociated ITP [was] probably caused by molecular mimicry.” Id. at 2. They also concluded that ITP was “strongly suspected” to be associated with the flu vaccine. Id. at 4.

Shalmovitz and Johar 34 described a 50-year-old man who developed Evans’ syndrome, which is the combination of ITP and autoimmune hemolytic anemia with no known underlying cause. Pet. Ex. 32 at 1. The patient had received a flu vaccine four days before his onset of symptoms. Id. The authors postulated that the flu vaccine, through molecular mimicry, may have been the cause of the patients Evans’ syndrome. Id. at 2. The authors performed a PubMed 35 search and came across eight case reports of patients who developed ITP after receiving a flu vaccine. Id. The authors opined that these case reports “suggest [] immunizations may provide a trigger for the development of autoimmune disease in susceptible individuals.” Id.

31 Moshe Tishler et al., Immune Thrombocytopenic Purpura Following Influenza Vaccination, 8 IMAJ 322 (2006). 32 Ryuichi Ohta & Chiaki Sano, Severe Immune Thrombocytopenic Purpura Following Influenza Vaccination: A Case Report, 14 Cureus 1 (2022). 33 Joji Nagasaki et al., Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients, 2016 Case Reps. Hematol. 1. This was also filed as Pet. Exs. 33, 83. 34 Gil Z. Shlamovitz & Sandeep Johar, A Case of Evans’ Syndrome Following Influenza Vaccine, 44 J. Emerg. Med. e149 (2013). This was also filed as Pet. Exs. 39, 82. 35 “PubMed is a free resource supporting the search and retrieval of biomedical and life sciences literature . . . . PubMed contains more than 40 million citations and abstracts of biomedical literature.” Nat’l Libr. Med., Nat’l Ctr. for Biotechnology Info., About PubMed, https://pubmed.ncbi.nlm.nih.gov/about/ (last visited June 17, 2026).

16

Mantadakis et al. 36 described a case report of a three-year-old boy who developed ITP 26 days after his second dose of the flu vaccine. Pet. Ex. 38 at 1. They postulated that the mechanism of thrombocytopenia following flu infection was most likely due to molecular mimicry. Id. at 2. The authors concluded that while there was a risk of ITP within six to eight weeks following the measles-mumps-rubella (“MMR”) vaccine, more evidence was needed to explore the connection between the flu vaccine and ITP. Id. at 2-3 (“In conclusion, although the link between ITP and [flu] vaccination is biologically plausible, there is insufficient evidence to indicate a causal relationship between [flu] vaccine and symptomatic thrombocytopenia.”).

And Hamiel et al. 37 described a four-and-one-half-year-old boy who presented in October 2013 with bleeding and his platelet count was severely decreased at 17,000. Pet. Ex. 76 at 1. A review of the child’s past medical records revealed that he had previously been hospitalized at age one-and-one-half years and three-and-one-half years of age with similar symptoms of bleeding. Id. at 2. All three of the child’s hospital admissions for ITP had taken place within one week of receiving a flu vaccine. Id. And all three times the child received the Fluarix trivalent flu vaccine. Id. After the last occurrence, the child did not receive any further annual flu vaccines, and no recurrences of ITP were observed. Id. Using the WHO standardized case causality assessment, the flu vaccine was determined to fall into the category of “certain” causality. Id.

Lastly, Dr. Ghose cited two cases where immunosuppressed patients developed ITP following flu vaccination. See Pet. Ex. 36; 38 Pet. Ex. 37. 39 However, there is no evidence

36 Elpis Mantadakis et al., A Case of Immune Thrombocytopenic Purpura After Influenza Vaccination: Consequence or Coincidence?, 32 J. Pediatr. Hematol. Oncol. e227 (2010). This was also filed as Pet. Ex. 106. 37 Uri Hamiel et al., Recurrent Immune Thrombocytopenia After Influenza Vaccination: A Case Report, 138 Pediatrics e1 (2016). 38 K. Ikegame et al., Idiopathic Thrombocytopenic Purpura After Influenza Vaccination in a Bone Marrow Transplantation Recipient, 38 Bone Marrow Transplant. 323 (2006). Ikegame et al. discussed a bone marrow transplant recipient whose platelet count rapidly decreased two weeks after flu vaccination. Pet. Ex. 36 at 1-2. At the time of vaccination, the patient was receiving low doses of tracrolimus (1.7 mg/day) (immunosuppressant) and prednisone (7 mg/day). Id. at 1. The authors suggested that the causal theory was molecular mimicry, stating “[a]cute ITP may [] occur after vaccination” because “[a]ntibodies responsible for the clearance of virus antigens may cross-react with antigens naturally present on platelets.” Id. at 2. 39 Satoshi Mamori et al., Thrombocytopenic Purpura After the Administration of an Influenza Vaccine in a Patient with Autoimmune Liver Disease, 77 Digestion 159 (2008). Mamori et al. described a 75-year-old patient with autoimmune liver disease (“AILD”) who received a flu vaccine. Pet. Ex. 37 at 1. One week after vaccination, the patient began experiencing symptoms and was diagnosed with ITP. Id. The authors concluded that “the [flu] vaccine can exacerbate potential immune-mediated platelet destruction in AILD patients, thus leading to severe autoimmune side effects.” Id. at 2.

17

Petitioner here was immunosuppressed at the time of vaccination, and thus, the relevance of these cases is unclear.

iii. Althen Prongs Two and Three

Dr. Ghose agreed Petitioner suffered acute ITP in October 2019 and opined her “flu vaccine more likely than not caused [her] ITP.” Tr. 11, 13; see also Pet. Ex. 10 at 6 (“Undoubtedly [Petitioner] developed acute ITP secondary to [flu] vaccination.”); Pet. Ex. 72 at 3 (“It is more likely than not that [Petitioner] developed ITP and chronic fatigue from the flu vaccine administered on October 16, 2019.”).

Dr. Ghose explained that “the flu vaccine caused [Petitioner’s] ITP because the very next day [after vaccination,] she started not feeling well and her platelets started dropping.” Tr. 14, 16. Thus, “before the vaccine, she was perfectly fine. Just after it, her platelets dropped and she started having . . . signs and symptoms [of ITP]. So it was . . . very obvious that . . . here, a vaccine led to the issue . . . .” Tr. 16.

He opined Petitioner did not have any previous medical history or precipitating events, other than the flu vaccination, that could have caused her ITP. Tr. 13-14; Pet. Ex. 10 at 6; Pet. Ex. 72 at 3.

He also cited to statements from Petitioner’s treating hematologist, Dr. Dammrich, who first saw Petitioner on October 23, 2019, and attributed Petitioner’s ITP to her flu vaccination, which he believed was significant. Pet. Ex. 10 at 3-4, 6; Tr. 15-17, 39. Petitioner continued to see Dr. Dammrich over the ensuing months, and he continued to attribute Petitioner’s ITP to her vaccination. Pet. Ex. 10 at 3-4, 6.

As to timing, Dr. Ghose opined Petitioner’s ITP onset was “within [one] day of receiving the [f]lu vaccine on October 16[,] 2019,” when her platelets dropped and she developed bruising and petechiae on her body and face and in her mouth. Pet. Ex. 10 at 6-7; Tr. 24-25, 27 (testifying Petitioner’s ITP symptoms began “[w]ithin a day” of her flu vaccination, “when the platelets drop[ped] significantly”).

On cross-examination, Dr. Ghose agreed Petitioner “began developing symptoms that eventually led to ITP” within ten minutes of vaccination when she developed tachycardia, and that her subsequent symptoms (e.g., chills, shakiness, shortness of breath) were also related to her ITP. Tr. 27-33. He clarified that these symptoms were evidence of “a strong immunological response” to the flu vaccine, meaning they are “related” to ITP “but [] not a symptom of ITP.” Tr. 29-30; see also Pet. Ex. 72 at 2-3 (classifying Petitioner’s initial symptoms as evidence of a hypersensitivity reaction 40 to the flu vaccine, which was then followed by a rapid drop in platelets). He agreed Petitioner developed ITP the same day as her flu vaccination. Tr. 35. He explained that Petitioner had petechiae at the site of injection, on her opposite arm, her face, and inside her mouth, which showed that her ITP developed the same day as the vaccination. Tr. 36.

40 Dr. Ghose does not define hypersensitivity reaction and appears to be relying on Dr. Akbari’s expert reports in making this statement. See supra note 22; infra Section II.C.2.b.

18

This timing, according to Dr. Ghose, “is characteristic of the autoimmune nature of the disease and confirms the causal relationship to the vaccine which caused the immune mediated drop in platelets.” Pet. Ex. 10 at 6-7 (“The fact that the platelets dropped within [one to two] days of the vaccination [] confirms the immune mediated nature of the disease that characterizes ITP.”). Additionally, because Petitioner had received prior flu vaccinations, Dr. Ghose opined her previous exposures “might be a reason why she developed an immediate hypersensitivity reaction.” Pet. Ex. 73 at 3.

Additionally, he asserted the literature shows ITP can develop between one and 35 days after vaccination. Pet. Ex. 10 at 6; Pet. Ex. 72 at 2-3. However, Dr. Ghose did not provide any literature to support an onset of ITP on the same day as flu vaccination, or within one day of flu vaccination, or that a one-day onset was an appropriate temporal interval for his posited theory of molecular mimicry.

A review of his literature shows cases of ITP post-flu vaccination occurring between four days and five weeks after vaccination. Jadavji et al. reported two cases of ITP, 10 and 14 days post-flu vaccination. Pet. Ex. 23 at 2, 2 tbl. 1. Tishler et al. reported a case of ITP 14 days after flu vaccination. Pet. Ex. 18 at 1. Ohta and Sano’s case of ITP occurred four days after a flu vaccination. Pet. Ex. 20 at 1. Nagasaki et al. described three cases of ITP occurring four to five weeks post-flu vaccination. Pet. Ex. 21 at 1-2. The patient discussed by Shalmovitz and Johar developed Evans’ syndrome four days after receiving a flu vaccine. Pet. Ex. 32 at 1. Mantadakis et al. described a child who developed ITP 26 days after his second flu vaccine. Pet. Ex. 38 at 1. And Hamiel et al. reported a child whose ITP symptoms began within one week of a flu vaccine on three separate occasions. Pet. Ex. 76 at 2.

2. Petitioner’s Expert, Dr. Omid Akbari 41

a. Background and Qualifications

Dr. Akbari is a Professor of Immunology at the University of Southern California, Keck School of Medicine. Pet. Ex. 40 at 2; Pet. Ex. 156 at 2. He received a Ph.D. in cellular and molecular immunology at the National Institute for Medical Research in London, United Kingdom. Pet. Ex. 156 at 1. Thereafter, he completed a postdoctoral fellowship at Stanford

41 Dr. Akbari provided three expert reports and testified at the entitlement hearing. Pet. Exs. 40, 88, 115; Tr. 3, 272. For sake of brevity, the undersigned does not discuss literature previously discussed above in Dr. Ghose’s expert section or literature that is not relevant to this case (i.e., literature that does not pertain to the flu vaccine or ITP). See, e.g., Pet. Ex. 69 (Sonal Prasad et al., Immune Thrombocytopenia Following COVID-19 Vaccine, 2022 Case Reps. Hematol. 1) (addressing a case of ITP following COVID vaccination); Pet. Ex. 71 (Meirong Zhu et al., IL-18 and IL-35 in the Serum of Patients with Sepsis Thrombocytopenia and the Clinical Significance, 19 Exp. & Ther. Med. 1251 (2020)) (examining IL-18 and IL-35 levels in the serum of patients with sepsis, with and without thrombocytopenia). Further, the undersigned does not discuss all aspects of Dr. Akbari’s reports and testimony and attempts to limit this Decision to only those aspects that are relevant.

19

University. Id. Dr. Akbari’s research focuses on the “the role of immune tolerance and how immune cells induce autoimmune and allergic diseases.” Pet. Ex. 40 at 2; see also Pet. Ex. 156 at 6-7. His laboratory research includes multiple studies regarding “how a vaccination can result in an appropriate or dysregulated immune response.” Pet. Ex. 40 at 2; see also Pet. Ex. 156 at 6- 7. Dr. Akbari serves as an associate editor and reviewer on several journals. Pet. Ex. 40 at 2; Pet. Ex. 156 at 5-6. He has authored or co-authored over 100 publications. Pet. Ex. 156 at 15- 34.

Dr. Akbari is not a medical doctor and thus, he does not diagnose or treat patients with ITP. See Pet. Ex. 156 at 1. He was admitted as an expert in immunology without objection. Tr. 82.

b. Opinion

i. Severity Requirement

Dr. Akbari agreed with Dr. Ghose that fatigue, an important aspect of health-related quality of life, can affect adults with ITP, even when in remission. Pet. Ex. 40 at 13. He opined Petitioner’s “persistent fatigue” was associated with her ITP. Id. at 4.

Dr. Akbari explained that induction of inflammasomes and the subsequent induction of molecular mimicry can lead to persistent fatigue in ITP patients. Pet. Ex. 40 at 13-14. He summarized that after flu vaccination, cytokines and inflammasomes are induced, which causes immune dysregulation that in turn induces fatigue in patients with ITP. Id. at 15.

He cited and discussed literature to support the association between fatigue and ITP. Pet.

Ex. 40 at 13-14; Tr. 133-38. Newton et al., 42 for example, examined fatigue in adult ITP patients, both with active disease and non-active disease, in the US and UK, to determine patient characteristics associated with fatigue. Pet. Ex. 64 at 1-2. The authors noted that although patients with primary ITP often report fatigue, hematologists rarely consider fatigue as a manifestation of ITP. Id. at 1. Newton et al. concluded that “[f]atigue is a common symptom among patients with ITP.” Id. Univariate analysis showed patient characteristics significantly associated with fatigue included platelet count, steroid treatment, and more, while duration of ITP was not associated with fatigue. Id. at 5. “Although the presence of fatigue was significantly associated with lower platelet counts, the relative frequency of fatigue among patients with platelet counts ≥ 100[,]000/µL[43] was also significantly greater than expected for normal subjects.” Id. at 5, 5 tbl. 2 (finding 32% of the UK cohort and 9% of the US cohort with a platelet count ≥ 100,000/µL reported fatigue, both of which were “significantly greater” than the expected frequency in normal subjects (2.5%)).

42 Julia N. Newton et al., Fatigue in Adult Patients with Primary Immune Thrombocytopenia, 86 Eur. J. Haematol. 420 (2011). 43 Patients’ platelet counts were based on patient recall. Pet. Ex. 64 at 2. Patients who reported “normal” platelet counts were considered to have a platelet count > 100,000/µL. Id.

20

ii. Althen Prong One

1. Overview

Dr. Akbari began by explaining how vaccines and the immune system work. Generally, after vaccination, there is a local inflammatory response mediated by cells involved in the innate immune system, which functions as a general, nonspecific response to activate the adaptive immune system, which in turn involve B and T cells (memory cells) that protect against subsequent exposures. Pet. Ex. 40 at 5; Tr. 84; see also Pet. Ex. 42 (generally describing how vaccines induce immune responses). 44 Upon flu vaccine administration specifically, inflammasomes are induced (e.g., IL-1 and IL-18) at the site of vaccination, which “starts a series of cascades that trigger more immune cells to the site” of vaccination, leading to an adaptive immune response where CD4 and CD8 T cells are activated and become memory cells within approximately two weeks. Tr. 85.

Dr. Akbari opined ITP is an immune-mediated disorder whose pathogenesis “has not been complete elucidated.” Pet. Ex. 40 at 6, 10; see also Pet. Ex. 88 at 14 (noting the pathogenesis of vaccine-related ITP “remains incompletely understood”). He explained ITP can occur immediately, “mainly mediated through innate induction of immune system,” or ITP can be explained “with induction of adaptive immune responses, including induction of B and T cells mainly through mechanism of molecular mimicry.” Pet. Ex. 40 at 6.

Dr. Akbari’s theory, summarized in the image below, involves both the innate and adaptive immune system:

44 Claire-Anne Siegrist, Vaccine Immunology, in Plotkin’s Vaccines 16 (7th ed. 2018).

21

Pet. Ex. 155. 45

To summarize, Dr. Akbari explained the first step after flu vaccination is activation of inflammasomes. Tr. 331.

Then, in the second step, inflammasome activation via dendritic cells (an antigen-

presenting cell or “APCs”) leads to “two pathways:” one is immediate hypersensitivity and the second affects platelets and megakaryocytes, which have IL-1 receptors that are recognized by dendritic cells for binding. Tr. 331-32, 334. IL-1β is a cytokine, a product of inflammasomes, and part of the innate immune system. Tr. 335, 337. IL-1β binds to the IL-1 receptors on platelets and megakaryocytes, which leads to apoptosis (cell death). Id. (explaining the IL-1β “cytokine can directly bind on the receptor and start the cascade that change the homeostasis of platelets” (citing Pet. Ex. 128)); see also Pet. Ex. 115 at 10.

The second pathway of step two (inflammasome activation and IL-1 receptors on platelets and megakaryocytes are recognized by dendritic cells (APCs) for binding) then leads to the third step of Dr. Akbari’s theory, which is when inflammasomes activate autoreactive B cells. Tr. 332. The IL-1β receptor is “very highly expressed on autoreactive B cells.” Tr. 335. He acknowledged that “it takes several days for conventional naïve B cells to get activated and produce IgM,” however, “for autoreactive B cell[s], . . . the activation threshold is very low,” and thus, activation would be faster. Tr. 332; see also Pet. Ex. 115 at 2-3. Dr. Akbari agreed that the third step, involving autoreactive B cells, is part of the adaptive immune system. Tr. 336.

The fourth and final step of his theory is the “production of IgM and direct activation of inflammasome binding to megakaryocytes and platelets to cause acute ITP.” Tr. 333, 336.

Thus, both the innate immune response and the adaptive immune response are involved in Dr. Akbari’s theory. Tr. 337; see also Pet. Ex. 88 at 8.

2. Innate Immune System, Inflammasomes, and Cytokines

Dr. Akbari opined he is “very [] certain that induction of inflammasome[46] by vaccines play[s] an important role as [an] initial trigger for the development of ITP.” Pet. Ex. 40 at 6; see also Tr. 84-86.

45 Dr. Akbari prepared this slide for the hearing. Tr. 331.

46 For more information on inflammasomes, see, for example, Pet. Ex. 88 at 8-9.

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For support, he cited literature reporting activation of inflammasomes after flu vaccination. 47 Pet. Ex. 40 at 6-8 (citing, e.g., Pet. Ex. 43); 48 see also Tr. 86. In Crooke et al., Dr. Akbari opined the authors demonstrated “inflammasome and subsequent production of IL-1 and related genes get sufficiently triggered[] by the flu vaccination[] in the absence of adjuvants.” Pet. Ex. 40 at 7 (citing Pet. Ex. 43 at 9). Crooke et al. evaluated inflammasome activity at baseline, 24 hours after flu vaccination, and 28 days after flu vaccination. Resp. Ex. 43 at 2. The authors noted “[flu] vaccination did not appear to have an immediate effect on macrophage inflammasome activity, although IL-1β levels were slightly elevated in unstimulated macrophages 24 h[ours] postvaccination compared to baseline.” Id. at 4. Additionally, “IL-1β secretion in response to [flu] stimulation at 24 h[ours] post-vaccination was higher in older adults.” Id. at 7. No “associations between inflammasome-mediated cytokine production and change in [HA inhibition] titer after vaccination” were observed. Id. at 6. Crooke et al. did not study or discuss ITP.

During the hearing, Dr. Akbari noted he and Dr. He agreed the flu vaccine is capable of inducing inflammasomes, and individuals’ responses to such inflammasomes can differ. Tr. 87- 88, 330; see Pet. Ex. 88 at 5-7; Pet. Ex. 96 at 1 (“[T]here was no evidence for a ‘universal signature’ that predicted antibody response to all vaccines.”). 49

He also cited literature, including Qiao et al., 50 to show “inflammasome[s] directly play a role in induction of ITP.” Tr. 87 (citing Pet. Ex. 47); see also Pet. Ex. 40 at 8. Of note, Qiao et al. stated that ITP is an “immune dysregulation-related disorder,” involving “dysregulation of T cell activity and related cytokines,” along with “the development of autoreactive B cells.” Pet. Ex. 47 at 1-2. They further explained that the decreased platelet count is a result of an “anti- platelet autoantibody-mediated immune response, leading to accelerated platelet destruction and impaired platelet production.” Id. at 5. The study provided evidence of a higher expression of inflammasomes (NLRP3 and others), suggesting that NLRP3 activation may play “a regulatory role . . . in inflammation and adaptive immune response.” Id. The authors concluded that

47 Dr. Akbari cited Wan et al. to show the flu infection can induce inflammasomes. Pet. Ex. 40 at 8; Tr. 87 (citing Pet. Ex. 44 (Pin Wan et al., AP-1 Signaling Pathway Promotes Pro-IL-1β Transcription to Facilitate NLRPP3 Inflammasome Activation upon Influenza A Virus Infection, 13 Virulence 502 (2022))). However, he did not explain how this information pertains to a flu vaccine considering the flu vaccine given here did not contain the live virus flu infection. See Tr. 139. 48 Stephen N. Crooke et al., Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults, 2 Front. Aging 1 (2021). This was also filed as Pet. Ex. 90. 49 Thomas Hagan et al., Transcriptional Atlas of the Human Immune Response to 13 Vaccines Reveals a Common Predictor of Vaccine-Induced Antibody Responses, 23 Nature Immunol. 1788 (2022). 50 Jianlin Qiao et al., Elevated Expression of NLRP3 in Patients with Immune Thrombocytopenia, 64 Immunol. Res. 431 (2016).

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“NLRP3 activation might be involved in the pathogenesis of ITP.” Id. at 6. However, the authors did not suggest that inflammasomes directly induce platelet destruction or that platelet destruction could occur absent the adaptive immune response.

Dr. Akbari also cited medical literature showing the flu vaccine increases levels of proinflammatory cytokines, which may be associated with local and systemic responses that occur shortly after vaccination. Pet. Ex. 40 at 9-10, 14. Christian et al., 51 for example, studied post-flu vaccination proinflammatory cytokine responses. Pet. Ex. 48 at 1. Serum cytokines were tested at days one through three after vaccination. Id. Injection site soreness and increases in two cytokines tested were elevated at one day post-vaccination. Id. Illness-like symptoms and serum cytokines were elevated at two days post-vaccination. Id. at 1-2. Christian et al. does not mention ITP.

Cytokines, Dr. Akbari explained, “play an important role in the induction of Th17 cells,”

which are elevated in patients with ITP. Pet. Ex. 40 at 14. In a supplemental expert report, Dr. Akbari opined “Th17 cells have the potential to trigger ITP.” Pet. Ex. 88 at 9. He explained that flu vaccination activates inflammasomes, which releases IL-1, “a pivotal cytokine that plays a central role in the differentiation and proliferation of Th17 cells.” Id. at 10. Th17 cells are “armed with the potential to cause ITP and contribute to pathological processes,” according to Dr. Akbari. 52 Id.

He cited Zhang et al., 53 who explained T cell abnormalities are important in the pathogenesis of chronic ITP. Pet. Ex. 66 at 1. Th17 cells are characterized by the production of IL-17, 54 and Th17 has been linked to the development of autoimmune diseases. Id. Zhang et al. suggested Th17 and Th1 cells “may” play a role in the pathogenic mechanism of ITP (whether that be cooperative or synergetic) and Th17 cells, which promote a cytokine imbalance, “may induce ITP.” Id. at 2-3. Further, they indicated their data “strongly supported the hypothesis that

51 Lisa M. Christian et al., Proinflammatory Cytokine Responses Correspond with Subjective Side Effects After Influenza Virus Vaccination, 33 Vaccine 3360 (2015). This was also filed as Pet. Ex. 91. 52 For more information about Th17 cells responses in the context of flu vaccination, see Pet. Ex. 88 at 10-11. Overall, Dr. Akbari opined Th17 cells have a “pivotal role” in the efficacy of vaccination. Pet. Ex. 88 at 11. Dr. Akbari also discussed regulatory T cells. See id. at 11-14. 53 Jingbo Zhang et al., Elevated Profile of Th17, Th1 and Tc1 Cells in Patients with Immune Thrombocytopenic Purpura, 94 Haematologica 1326 (2009). 54 See Pet. Ex. 68 (Yinyao Lin et al., Th17 Cytokines and Vaccine Induced Immunity, 32 Semin Immunopathol. 79 (2010)).

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cytotoxic T lymphocyte-mediated cytotoxicity[55] was an alternative mechanism for platelet destruction in ITP.” Id. at 3.

2. Adaptive Immune System and Molecular Mimicry

Dr. Akbari opined “molecular mimicry is accepted as a theory to explain causation of autoimmune disease such as ITP.” 56 Pet. Ex. 40 at 11. He explained molecular mimicry is an “immunological process of cross-reactivity” or the “sharing of antigens between a host and a microorganism.” Id. He defined molecular mimicry as a “mechanism by which an immune stimulated response by infection or other method, i.e. vaccination, can trigger cross-reactive antibodies or T cells that cause the symptoms of autoimmune disease.” Id.

Dr. Akbari acknowledged that direct sequence homology between the flu vaccine and ITP is not known. Pet. Ex. 40 at 11-2. But “despite no obvious amino acid sequence similarity,” he asserted “mimicry can still happen at the host level.” Id. at 12. “Molecular mimicry is thus occurring between two recognized peptides that have similar antigenic surfaces in the absence of primary sequence homology.” Id. at 13.

Specific to this case, Dr. Akbari testified that the inflammasomes induced by the flu vaccine directly activate autoreactive B cells 57 which produce IgM. Tr. 92. “Then[,] at the same time, . . . inflammatory induction not only help[s] these autoreactive B cells and T cells, [] they can [also] directly affect the generation and homeostasis of platelets.” Tr. 92-93. On cross- examination, he specified that the molecular mimicry aspect of his theory focuses on IgM produced from autoreactive B cells. Tr. 116; see also Pet. Ex. 155 (step three).

He opined severe and persistent cases of ITP are associated with T cells, while cases like Petitioner’s are not due to “B cells lack[ing] adequate T cell assistance.” Pet. Ex. 88 at 15-16. He explained that “B cells and antibodies may recognize self-proteins shortly after their formation. Unlike T cells, B cells do not require antigen-presenting cells for activation and can directly bind antigens with membrane-bound antibodies. Significantly, B cells also function as

55 Cytotoxic T lymphocyte-mediated cytotoxicity is an immune process by which T cells kill their targets (other cells) by inducing apoptosis (cell death). T Cell-Mediated Immunity, in Immunobiology: The Immune System in Health and Disease (Charles A. Janeway et al. eds., 5th ed. 2001), https://www.ncbi.nlm.nih.gov/books/NBK27101/; Glossary, in Immunobiology: The Immune System in Health and Disease, supra, https://www.ncbi.nlm.nih.gov/books/NBK10759/. 56 For general information on molecular mimicry, see, for example, Pet. Ex. 55 (Molecular Mimicry: Infection-Inducing Autoimmune Disease (M.B.A. Oldstone ed., 2005)); Pet. Ex. 56 (Robert S. Fujinami et al., Molecular Mimicry, Bystander Activation or Viral Persistence: Infections and Autoimmune Disease, 19 Clin. Microbiol. Revs. 80 (2006)). 57 Autoreactive B cells recognize and respond to self-antigens (autoantigens). See Autoreactive, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=5033 (last visited June 17, 2026).

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antigen-presenting cells.” Id. at 16. This, according to Dr. Akbari, leads to ITP, albeit less persistent cases of ITP due to the lack of T cell involvement, “within hours in some individuals.” Id.; Pet. Ex. 115 at 6-7. Dr. Akbari provided no support for his opinion that onset of ITP could occur within 24 hours if there is a lack of T cell involvement, or that molecular mimicry could induce platelet destruction within one day.

Dr. Akbari summarized

the mechanism underlying this rapid response involves the complex interplay between the innate and adaptive immune systems. The inflammasome arm, a component of the innate immune system, when activated by vaccines, can enhance the activity of autoreactive B cells. These B cells, part of the adaptive immune system, produce antibodies that mistakenly target the body’s own tissues, leading to adverse outcomes within [a] few hours.

Pet. Ex. 88 at 16 (emphasis omitted).

In his third report, he provided additional information to support his proposed mechanism of autoreactive B cell molecular mimicry. Pet. Ex. 115 at 2-8. He explained that autoreactive B cells and conventional B cells are distinct. Id. at 2-3; Tr. 93-94. Conventional B cells are part of the adaptive immune system, are “responsible for producing antibodies that specifically target and neutralize pathogens,” and antibody production and response “takes several days.” Pet. Ex. 115 at 2-3. In contrast, he opined that autoreactive B cells “mistakenly recognize and react against the body’s own tissues, leading to autoimmunity,” and can be “[f]ast-acting.” Id. Dr. Akbari added that conventional B cells “usually require help from T cells to become fully activated,” while autoreactive B cells do not. Id. at 3.

Citing van den Broek et al., 58 Dr. Akbari opined “the process of autoreactive B cells responding to antigen and contributing to the immune response can occur within a few hours.” Pet. Ex. 115 at 3 (citing Pet. Ex. 116). However, the authors do not make this finding, they do not discuss vaccination or flu vaccination, nor is ITP mentioned. Thus, the relevancy of this article is unclear. And Dr. Akbari did not provide any other literature to support these opinions.

At the hearing, Dr. Akbari again opined autoreactive B cells act within minutes. Tr. 94.

For support, he explained autoreactive B cells produce IgM and cited a figure in Cines et al. 59 showing IgM levels in ITP patients. Tr. 94-95; Pet. Ex. 115 at 5; Pet. Ex. 117 at 5 fig.7. Dr. Akbari opined that this figure suggested “IgM fast-producing antibodies from autoreactive B cells are basically associated with ITP.” Tr. 95. However, the study was not related to how long it took autoreactive B cells to act/activate. The authors studied ITP patients “for the presence of

58 T. van den Broek et al., Invasion of Spontaneous Germinal Centers by Naïve B Cells Is Rapid and Persistent, 2023 bioRxiv [Preprint] 1, https://www.biorxiv.org/content/10.1101/2023.05.30. 542805v2. This appears to be a preprint and the source is not clear. 59 Douglas B. Cines et al., Platelet Antibodies of the IgM Class in Immune Thrombocytopenic Purpura, 75 J. Clin. Invest. 1183 (1985).

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IgM anti-platelet antibodies” and found these antibodies in some of the patients with ITP. Pet. Ex. 117 at 1. The study does not support rapid onset of ITP consistent with the facts of this case. Further, it does not relate to vaccination.

3. Additional Medical Literature

Dr. Akbari agreed ITP post-flu vaccination is rare, but emphasized that “rarity does not negate the potential for adverse effects.” Pet. Ex. 88 at 15.

Like Dr. Ghose, Dr. Akbari cited to Garbe et al. and Mantadakis et al. as support that the flu vaccine can cause ITP. Pet. Ex. 40 at 10 (citing Pet. Ex. 53); Pet. Ex. 88 at 14; see also Tr. 99-101 (citing Pet. Exs. 38, 53).

He also cited a study from Huang et al., 60 which examined passive reports of adverse events following the 2009 H1N1 vaccine in Taiwan. Pet. Ex. 40 at 10 (citing Pet. Ex. 52 at 1); Pet. Ex. 88 at 14. ITP was included as an adverse event. Pet. Ex. 52 at 2. The authors made no findings or conclusions about an association between ITP and the H1N1 vaccine or increased risk of ITP post-H1N1 vaccination.

The authors in Cecinati et al. 61 noted that “[v]accine-related thrombocytopenia is considered to be of immune origin because antibodies can be detected on platelets in about 79% of cases.” Pet. Ex. 105 at 1. Based on data from surveillance systems, they reported that cases of ITP following vaccination are generally infrequent and less severe. Id. at 2. The authors also noted that the “[t]rivalent inactivated [flu] vaccine [] has been associated with ITP in a very small number of adult case reports,” as well as a surveillance study by Garbe et al. Id. at 3 (citing Pet. Ex. 53).

Dr. Akbari also cited Nakayama and Onoda, 62 who examined cases reported in the postmarketing surveillance of the Kitasato Institute and noted two ITP cases were reported among 38.02 million doses of the flu vaccine. Pet. Ex. 108 at 1, 5. The authors made no findings related to flu vaccination and ITP.

60 Wan-Ting Huang et al., The Reporting Completeness of a Passive Safety Surveillance System for Pandemic (H1N1) 2009 Vaccines: A Capture–Recapture Analysis, 30 Vaccine 2168 (2012). This was also filed as Pet. Exs. 103, 146. 61 Valerio Cecinati et al., Vaccine Administration and the Development of Immune Thrombocytopenic Purpura in Children, 9 Hum. Vaccines & Immunotherapeutics 1158 (2013). 62 Tetsuo Nakayama & Kazumasa Onoda, Vaccine Adverse Events Reported in Post-Marketing Study of the Kitasato Institute from 1994 to 2004, 25 Vaccine 570 (2007).

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Lastly, Dr. Akbari cited a case report from Yamamoto et al. 63 of severe thrombocytopenia within one day of flu vaccine with diffuse alveolar hemorrhage leading to respiratory failure. Pet. Ex. 115 at 17 (citing Pet. Ex. 145). The authors stated that “[t]he onset of vaccine-related ITP has a strict time relationship, developing within 4-35 days after [flu] vaccination.” Pet. Ex. 145 at 4. Theu further noted that “although [the patient] had potentially been sensitized by [a] previous vaccination, vaccine-related ITP may also have been incompatible given the too-short latency time. Other pathogeneses of thrombocytopenia might therefore have been involved; however, the pathogenesis of vaccine-related thrombocytopenia remains unknown.” Id. They concluded that the role of the flu vaccine “remains unclear, and further investigations are required.” Id.

iii. Althen Prongs Two and Three

Dr. Akbari opined “more likely than not” the flu vaccination caused Petitioner’s ITP via molecular mimicry and induction of inflammasomes. Tr. 80; Pet. Ex. 40 at 1; Pet. Ex. 88 at 27; Pet. Ex. 115 at 18.

He summarized that “[Petitioner,] as a result of receiving a[] [flu] vaccine on October 16, 2019, first developed immediate hypersensitivity,[64] as evident by symptoms such as shivering, petechiae at the site of the injection, on her face, and inside her mouth,” which are “signs [] associated with induction of inflammasome and related pathways, induced by [flu] vaccine,” and which resulted in ITP. Pet. Ex. 40 at 4, 17-18; see also Tr. 98-99, 114-15. Dr. Akbari added that delayed hypersensitivity reactions 65 in ITP (e.g., petechiae, chills, fever, fatigue, nausea, and tachycardia), often occur within hours or days after vaccine administration and are accompanied by a variety of cytokines, chemokines, and complements. Pet. Ex. 40 at 5; see also Tr. 103-04.

Dr. Akbari opined this timing supports the flu vaccine as the most logical sequence of cause and effect. Pet. Ex. 40 at 17-18. He postulated that ITP occurring within one day of flu vaccination “suggests that either autoreactive B cells and/or innate cells were involved in the induction of ITP.” Pet. Ex. 115 at 6-7; see also Tr. 122; Pet. Ex. 88 at 27 (concluding “the timing between the vaccine administration and the symptom development aligns with the role of

63 Yuji Yamamoto et al., Influenza Vaccination-Associated Acute Thrombocytopenia and Diffuse Alveolar Hemorrhage, 59 Intern. Med. 1633 (2020). 64 An immediate hypersensitivity reaction is a “mediated by antibodies and develop[s] rapidly, generally in minutes to hours,” and can be “distinguished from those mediated by T lymphocytes and macrophages and generally requiring 24 to 72 hours to develop ( . . . sometimes called delayed hypersensitivity [reactions]).” Immediate Hypersensitivity Reaction, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=102389 (last visited June 17, 2026). 65 A delayed hypersensitivity reaction is “a reaction of cell-mediated immunity, named in contrast to immediate hypersensitivity reactions because its onset is 24 to 72 hours after the antigenic challenge.” Delayed Hypersensitivity Reaction, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=102357 (last visited June 17, 2026).

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B cells and induction of inflammasome, establishing a logical sequence of cause and effect between [Petitioner’s] vaccination and [her] subsequent adverse reactions”). “The rapid induction of inflammasome within a short timeframe leads to robust immune responses triggered by molecular mimicry, which can subsequently aggregate symptoms associated with ITP.” Pet. Ex. 88 at 27.

Dr. Akbari opined Petitioner’s vaccine contained HA from several strains of the flu virus, including the H1N1 proteins measured in Crooke et al. Pet. Ex. 40 at 8. However, he did not cite any support for this statement. At the hearing, Dr. Akbari agreed Petitioner’s flu vaccine did not contain a live virus. Tr. 139. Although Petitioner’s vaccine record indicated she received a quadrivalent flu vaccination (Flucelvax), no package insert was provided to show the viral strains or specific ingredients of Petitioner’s vaccine. See Tr. 139-40; Pet. Ex. 1 at 26.

Additionally, Dr. Akbari testified that there was no alternative cause for Petitioner’s ITP.

Tr. 101.

As to timing, Dr. Akbari opined Petitioner’s onset of symptoms was a “few hours” after her flu vaccination as evidenced by her hypersensitivity reactions. Pet. Ex. 40 at 18; Tr. 102-03. The hypersensitivity reactions were then “followed by induction of ITP [a] few days after administration of flu vaccine.” Pet. Ex. 40 at 18.

At the hearing, however, he placed onset of Petitioner’s ITP when Petitioner’s blood work showed her low platelet level, which was within or around one day but not within hours. Tr. 107, 126. He opined Petitioner did not have ITP prior to receiving her platelet count of five the day after vaccination. Tr. 126.

He testified that this timing (one day) is medically appropriate because inflammasomes, which are part of the innate immune system, peak at one day. Tr. 107, 120; Pet. Ex. 40 at 18. He cited Christian et al. to support a one-day onset. Tr. 104-06 (citing Pet. Ex. 48 at 11 fig. 1). However, Christian et al. examined only local reactions post-vaccination and serum proinflammatory cytokines when finding cytokines elevated one-day post-vaccination. See Pet. Ex. 48 at 11 fig. 1. Timing as it relates to an adaptive immune response was not discussed or studied in Christian et al. See id. Dr. Akbari did not acknowledge the other steps of his theory that he asserted must take place in order for platelets to be destroyed, including aspects that require induction of the adaptive immune system. See, e.g., Pet. Ex. 155 (demonstrative showing Dr. Akbari’s four-step theory).

Additionally, he testified that the timing between vaccination and onset depends on the type of vaccine and patient; “it can happen within a few minutes to . . . a few months.” Tr. 102- 03. However, he also testified that several reports of ITP following various vaccinations have shown an acceptable time frame to be “within one day to a few weeks.” Tr. 107.

Dr. Akbari acknowledged “a primary antibody response is evident within one to two weeks after vaccination. During this period, . . .autoreactive B cells, if present, can also become activated. This rapid response is crucial for providing immediate protection against the virus but also means that any potential autoreactivity can manifest relatively quickly.” Pet. Ex. 115 at 6.

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However, Petitioner’s “rapid response” was within one day, not one to two weeks post- vaccination.

Lastly, Dr. Akbari admitted that “[he] believe[d], the significance of a temporal relationship, denoting a close proximity in time between vaccination and the emergence of symptoms or injury, stands out as one of the most compelling aspects in the context of this case.” Pet. Ex. 115 at 17.

3. Respondent’s Expert, Dr. Lisa Baumann Kreuziger 66

a. Background and Qualifications

Dr. Baumann is board certified in hematology and oncology. Resp. Ex. A at 1; Resp. Ex.

H at 3. She graduated from the University of Wisconsin-Madison, School of Medicine and Public Health in 2006 with her M.D. and thereafter completed an internal medicine residency at the Mayo Clinic, a fellowship at the University of Minnesota, and an M.S. in clinical research at the University of Minnesota. Resp. Ex. H at 1. Since 2013, Dr. Baumann has held various faculty, administrative, and hospital staff appointments. Id. at 2. She has authored or co- authored over 100 publications. Id. at 19-29.

Dr. Baumann “routinely care[s] for patients with hematologic disorders including [ITP]”

and “ha[s] treated over 30 patients with ITP.” Resp. Ex. A at 1. She was admitted, without objection, as an expert in hematology and epidemiology. Tr. 279.

b. Opinion

i. Severity Requirement

Dr. Baumann explained that “ITP is an autoimmune disorder where the immune system is activated against and destroys platelets.” Tr. 279. Clinically, ITP manifests with low platelet counts and bleeding. Tr. 280. According to Dr. Baumann, ITP patients are considered to have “active ITP” when their platelet counts are low. Tr. 308, 314. Thus, “[w]hen platelet counts are normal, ITP is not active.” Tr. 314.

First, Dr. Baumann does not dispute that “fatigue is associated with active ITP.” Tr. 308;

see also Tr. 312 (agreeing “[f]atigue is a symptom of active ITP”). She noted she routinely questions her patients about fatigue. Tr. 288. She explained that “when platelet counts are low, fatigue can be present,” and the fatigue could be due to the disease or disease-related treatment. Tr. 288-89. However, she opined that when patients do not have active disease (i.e., when platelet counts are normal), complaints of fatigue are not due to ITP. Tr. 290, 313-14 (testifying that “if somebody would tell [her] that they had fatigue and their platelet count was normal, [] [she] would tell them [] that their fatigue is not due to ITP”).

66 Dr. Baumann provided two expert reports and testified at the entitlement hearing. Resp. Exs. A, C; Tr. 272.

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She explained that if an ITP patient is complaining of fatigue when they have normal platelet counts, “[she] would look at the patient’s hemoglobin, because anemia or low hemoglobin can also cause fatigue. If that’s also normal, [she] would . . . look at iron, [and] the other things that are within the hematology purview that cause fatigue.” Tr. 289. If those are also normal, she would then tell her patients that there is not a “blood reason for [their] fatigue” and other, non-blood related reasons could be a potential cause of their fatigue, as “fatigue is caused by a lot of things.” Tr. 288-89.

As to Petitioner specifically, Dr. Baumann opined Petitioner “experienced acute ITP . . .

from 10/17/19 to 10/23/19,” a total of six days, and since then, she “has had normal platelet counts and no further reports of petechiae, spontaneous bruising, or gum bleeding.” Resp. Ex. A at 5, 9; see also Resp. Ex. C at 7-8; Tr. 285-86. Thus, Dr. Baumann opined Petitioner has not suffered from active ITP since October 23, 2019. Tr. 286, 288, 294.

Regarding Petitioner’s argument that she had fatigue due to her ITP that lasted more than six months, Dr. Baumann disagreed and opined “[f]atigue was noted intermittently prior to vaccination and the assertion that it persisted [more than] [six] months after vaccination was not corroborated by [Petitioner’s] physicians or in the documentation she filled out prior to physical therapy” in June 2020 for an unrelated issue. Resp. Ex. A at 6, 9; see also Resp. Ex. C at 6-8.

She first noted “[f]atigue can be due to multiple factors” and Petitioner had documented episodic fatigue prior to her flu vaccination. Resp. Ex. A at 6 (citing Pet. Ex. 2 at 2, 6, 18); Resp. Ex. C at 6 (“The symptom of fatigue reported by [Petitioner] does not correlate to the pathophysiology of fatigue in ITP due to activation of the inflammasome because fatigue preceded her diagnosis of ITP . . . .”).

Next, Dr. Baumann discussed how the medical records do not support Petitioner’s assertion that she experienced fatigue for more than six months. Resp. Ex. A at 6; Resp. Ex. C at 6-7; Tr. 296-99. In May 2020, fatigue was not mentioned or documented during a telehealth visit with Dr. Dammrich, though an email from Petitioner to her counsel later that month did document fatigue. Resp. Ex. C at 7 (citing Pet. Ex. 5 at 36-37; Pet. Ex. 6 at 1). In June 2020, Petitioner filled out records for her knee surgery, and in these handwritten records, she did not mark she was suffering from “fatigue.” Tr. 296-98 (citing Pet. Ex. 8 at 32; Pet. Ex. 9 at 54); Resp. Ex. C at 7. Because “she had the ability . . . to write [fatigue] herself, and it was not noted,” Dr. Baumann opined Petitioner was not suffering from fatigue in June 2020. Tr. 298-99. And at another visits with Dr. Dammrich in June 2020, he wrote Petitioner’s “platelet count has remained normal as of end of May and she has no symptoms to suggest it has fallen.” Resp. Ex. C at 7 (quoting Pet. Ex. 4 at 14). Fatigue was not mentioned at that visit. Id.

Thus, she concluded “there is not corroborated evidence that an effect of ITP persisted for [six] months, particularly in the continued presence of normal platelet counts” as well as a lack of need for medication. Resp. Ex. A at 6; see also Resp. Ex. C at 7.

Dr. Baumann acknowledged that Petitioner complained of fatigue in November 25, 2019, as documented in her medical records, despite having normal platelet counts and no longer

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receiving ITP treatment (steroids) at that time. Tr. 316. She did not further comment on this record.

Lastly, Dr. Baumann addressed literature cited by Dr. Ghose regarding fatigue in the presence of ITP. Dr. Baumann opined that Dr. Ghose’s literature linking fatigue to ITP applies to only those with active ITP. Tr. 308, 314. And this literature, Dr. Baumann added, pertains only to patients with chronic ITP, as they are “easier to study.” Tr. 309; see also Resp. Ex. A at 5. Thus, she opined that this literature only “tells us [] that when ITP is active, there is evidence of impacts on fatigue and quality of life,” which she does not dispute. Tr. 308-09, 312.

For example, Dr. Baumann noted McMillan et al., cited by Dr. Ghose, was a study that examined impact to quality of life in patients with chronic ITP. Resp. Ex. A at 6 (citing Pet. Ex. 12). She noted that the authors documented study limitations, including the failure of the study to look at “how much of the reduced [health related quality of life] in ITP was related to the disease itself (e.g., lack of energy that is often reported by patients and appears to be related to a low platelet count) rather than effects of treatment.” Id. (quoting Pet. Ex. 12 at 4). “In addition, measurement of platelet counts was not one of the study assessments, thus correlations between platelet counts and [health related quality of life] scores could not be examined.” Pet. Ex. 12 at 4. McMillan et al. do not indicate their study pertains only to patients with chronic ITP.

On cross-examination, Dr. Baumann was questioned about a review from Al-Samkari and Kuter. 67 Tr. 314-15 (citing Resp. Ex. A2). The authors noted fatigue was “[t]he most common symptom in ITP aside from bleeding” and is seen in 20-40% of patients. Resp. Ex. A2 at 2. They further wrote, “[a]lthough the etiology is not entirely clear, fatigue can markedly affect quality of life in ITP patients and may even be an indication for treatment, which may be very effective at alleviating fatigue.” Id. Dr. Baumann maintained that fatigue resolved with higher platelet counts. Tr. 315.

Dr. Baumann was also questioned on cross-examination about Grace et al. and agreed that the authors surveyed both acute and chronic ITP patients. Tr. 316 (citing Pet. Ex. 153). She further agreed that the authors noted “[f]atigue scores at [one] and 12 months did not differ significantly depending on whether patients were platelet responders to therapy.” Tr. 317 (quoting Pet. Ex. 153 at 6).

ii. Althen Prong One

According to Dr. Baumann, “ITP is an autoimmune disorder and why autoimmunity occurs is not fully understood for most autoimmune diseases.” Tr. 311; see also Resp. Ex. A at 6.

Dr. Baumann explained “[t]he autoimmune mechanism at play in ITP is an activation of [] T cells, which can directly kill platelets, and [] B cells, which produce autoantibodies against

67 Hanny Al-Samkari & David J. Kuter, Immune Thrombocytopenia in Adults: Modern Approaches to Diagnosis and Treatment, 46 Semin. Thromb. Hemost. 275 (2020).

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platelets. Anything with an antibody on it, [the] body then recognizes that to be destroyed.” Tr. 318. T cells “can kill platelets once they’re activated,” which “generally takes minimum of [five] to 10 to 14 days” with the adaptive immune system. Tr. 318-19. With autoantibodies, the timing of their production depends on whether it is a primary exposure (seven to 14 days) or secondary exposure (about three days). Tr. 319-20. She opined the mechanism by which ITP occurs would be the same regardless of the inciting agent. 68 Tr. 322.

As for Dr. Ghose’s theory of molecular mimicry, Dr. Baumann opined “molecular mimicry is not a scientifically reliable mechanism by which [the flu] vaccine could cause ITP.” Resp. Ex. A at 8. She took issue with the fact that Dr. Ghose did not provide any information as to how molecular mimicry could occur, or more specifically, that he did not indicate a similar molecular structure between the flu vaccine and platelet antigens, which she acknowledged has not been identified despite extensive research. Id.

Dr. Akbari and Dr. Ghose also posited a hypersensitivity/inflammasome theory to account for Petitioner’s symptoms beginning within 24 hours of vaccination, which Dr. Baumann also disagreed with. Resp. Ex. C at 5-6. She cited to Siegrist to show the process by which the immune system responds to vaccination, which “extends well beyond 24 hours.” Id. at 5 (citing Pet. Ex. 42 at 6 fig. 2.1, 9 fig. 2.3). Specifically, Siegrist explained the process that occurs following vaccination:

Following injection (1), the pathogen-associated patterns contained in vaccine antigens attract dendritic cells, monocytes, and neutrophils that patrol throughout the body (2). Elicitation of sufficient “danger signals” by the vaccine antigens []/adjuvants [] activates monocytes and dendritic cells (3); the activation changes their surface receptors and induces their migration along lymphatic vessels (4), to the draining lymph nodes (5) where the activation of T and B lymphocytes will take place.

Pet. Ex. 42 at 6 fig. 2.1.

Dr. Baumann also criticized other literature from Dr. Akbari and Dr. Ghose and opined “a reliable and more likely than not mechanism of how inflammasome activation leads to thrombocytopenia within 24 hours was not provided.” Id. at 6.

Even though she agreed there is an “associated link” between the MMR vaccine and ITP, Dr. Baumann opined it is not permissible to impute that data to other vaccines like the flu vaccine, in part because the MMR vaccine is a live vaccine and the flu vaccine is not. Tr. 300-

68 For more information on the mechanism by which platelets are destroyed and produced, see, for example, Resp. Ex. A1 (Maurice Swinkles et al., Emerging Concepts in Immune Thrombocytopenia, 9 Front. Immunol. 1 (2018)); Resp. Ex. A15 (Renata Grozovsky et al., Regulating Billions of Blood Platelets: Glycans and Beyond, 126 Blood 1877 (2015)).

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01; Resp. Ex. A at 8; see also Resp. Ex. A17 (reviewing how different vaccine types generate immune responses). 69

She agreed the flu infection, as well as other infections, can cause ITP. Tr. 311-12; Resp.

Ex. A at 6. As to flu infection specifically, she cited literature that has shown the flu virus must be present for thrombocytopenia to occur. Resp. Ex. A at 8 (citing Resp. Ex. A16). 70 Kazatchkine et al. evaluated how antibodies could cause complement-mediated platelet lysis. Resp. Ex. A16 at 1. Their study showed “incubation of human platelets with suspensions of [flu] virus, but not with bacterial neuraminidase, results in completement and antibody-mediated lysis of platelets . . . [with] [t]he crucial event [being] the interaction of immunoglobulins with a viral [HA] present on the platelet membrane.” Id. at 1-2. Dr. Baumann cited this article to show “[v]iral replication does not occur after [flu] vaccination because [the vaccine uses] an inactivated virus and thus viral [HA] is not present in significant amounts to bind to the platelet surface.” Resp. Ex. A at 8 (citing Resp. Ex. A16). Therefore, the flu vaccine is not likely to cause ITP because it is an inactivated vaccine. Id.

Next, Dr. Baumann addressed the epidemiological evidence between the flu vaccine and ITP and concluded “the preponderance of evidence from well controlled and large studies has not found as association between [flu] vaccination and ITP.” Resp. Ex. A at 7; see also Tr. 303. She acknowledged there was one study (Garbe et al.) that suggested a “potential association,” however, she opined “there were biases within that study” 71 and subsequent studies have not shown an association between the flu vaccine and ITP. Tr. 303 (citing Pet. Ex. 53); see also Resp. Ex. C at 4.

Dr. Baumann discussed a large case control study by Grimaldi-Bensouda et al. 72 that did not find an association between the flu vaccine and ITP. Tr. 306-07 (citing Resp. Ex. A9). Grimaldi-Bensouda et al. conducted a large case control study in France with 198 ITP cases and 878 controls, of which 66 ITP cases and 303 controls received a vaccination within 12 months of “index date” (i.e., symptom onset). Resp. Ex. A9 at 1, 3. There was no evidence of an increase in ITP after vaccination in the previous six and 12 months, and though there was a higher odds ratio for all vaccines within the two-month period of onset, the increase was not statistically significant. Id. at 1, 3-4, 5 tbl. 3. The authors concluded that common vaccines, including the flu vaccine, are not associated with a risk of developing ITP. Id. at 1, 5.

69 David Baxter, Active and Passive Immunity, Vaccine Types, Excipients and Licensing, 57 Occup. Med. 552 (2007). 70 Michel D. Kazatchkine et al., Membrane-Bound Hemagglutinin Mediates Antibody and Complement-Dependent Lysis of Influenza Virus-Treated Human Platelets in Autologous Serum, 74 J. Clin. Invest. 976 (1984). 71 For these biases, see Tr. 305-06; Resp. Ex. C at 4.

72 Lamiae Grimaldi-Bensouda et al., A Case-Control Study to Assess the Risk of Immune Thrombocytopenia Associated with Vaccines, 120 Blood 4938 (2012). This was also filed as Resp. Ex. D6.

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Dr. Baumann next cited Rajantie et al. 73 Resp. Ex. A11. In Rajantie et al., 506 Nordic children (up to age 14) were diagnosed with ITP during a three-year period. Id. at 1. The authors studied only those patients whose onset of ITP occurred within one month of vaccination (35 total patients). Id. at 1-2. None of the children received the flu vaccine. 74 Id. at 2. Thus, the relevancy of this study to this case is not clear.

O’Leary et al. 75 examined the risk of ITP after childhood vaccinations other than MMR.

Resp. Ex. A12 at 1. The authors identified a cohort of 1.8 million children aged six weeks to 17 years, and within that cohort, there were 197 confirmed cases of ITP. Id. at 1-3. The authors found “no increased risk of ITP after vaccines other than MMR in young children.” Id. at 1. In older children, they found “ITP may occur after certain other vaccines,” however, this did not include the flu vaccine. Id. at 1, 6. For cases of ITP after the trivalent flu vaccine specifically, the authors found “several [incident rate ratios] that approached statistical significance in older children,” though “estimates in older children are less stable because there are fewer cases of ITP on which to perform analyses.” Id. at 4.

And lastly, she cited Lafaurie et al., 76 a French study that found no increased risk of ITP following flu vaccination when using three different designs and multiple sensitivity analyses. Resp. Ex. C at 4 (citing Resp. Ex. C1). Their main limitation, according to the authors, was that the patients in their study were those with the “most severe” ITP, while mild and transient ITP patients were not included. Resp. Ex. C1 at 2.

Overall, she summarized that there was “one flawed case control study [that] suggested an association between [flu] vaccination and ITP” and “three large case-control studies and one cohort study [that] did not find an association.” Resp. Ex. C at 4. Dr. Baumann concluded “these large well controlled studies are evidence that there is more likely than not no association between [flu] vaccination and ITP.” Id.

As for Dr. Ghose’s case reports, she testified that case reports are not sufficient to show an association between an inciting event and an outcome; they are used to “generate hypotheses”

73 J. Rajantie et al., Vaccination Associated Thrombocytopenic Purpura in Children, 25 Vaccine 838 (2007). 74 In Nordic countries, “[p]ersons 65 years and above, pregnant women[,] and persons with certain underlying diseases (including children) are recommended [to have] annual, seasonal vaccination against [flu].” Recommended Vaccinations, Publ. Health Agency Swed., https://www.folkhalsomyndigheten.se/the-public-health-agency-of-sweden/communicabledisease -control/vaccinations/recommended-vaccinations/ (last updated Sept. 1, 2025). 75 Sean T. O’Leary et al., The Risk of Immune Thrombocytopenic Purpura After Vaccination in Children and Adults, 129 Pediatrics 248 (2012). 76 Margaux Lafaurie et al., Risk of Immune Thrombocytopenia After Influenza Vaccine, 182 JAMA Internal Med. 444 (2022). This was also filed as Resp. Ex. D5.

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and to show the scientific community what needs to be looked into further. Tr. 300; see also Resp. Ex. A at 7, 9. Thus, she opined that case reports do not show causation between the flu vaccine and ITP. Tr. 302. She concluded “the weight of the medical literature does not support an association between the [flu] vaccination and ITP.” Resp. Ex. A at 9.

iii. Althen Prongs Two and Three

Dr. Baumann opined Petitioner’s October 16, 2019 flu vaccination did not cause her to develop ITP. Tr. 309-10; Resp. Ex. A at 7, 9; Resp. Ex. C at 8. Her opinion is based on three reasons: (1) “there is no reliable and more likely than not mechanism demonstrated by which the [flu] vaccination can cause ITP;” (2) “the timing of onset does not support the association between vaccination and ITP for [Petitioner];” and (3) the “weight of medical literature favors that there is no relationship between ITP and the [flu] vaccine.” Resp. Ex. A at 7.

She agreed Petitioner did not have any pre-existing conditions, infections, or other etiologies that could have caused her ITP, although “[she] was not tested for viral infections or other underlying etiologies.” Resp. Ex. A at 6 (“Without a known association, she would be considered to have primary ITP.”); see also Tr. 312.

As for timing, Dr. Baumann opined Petitioner developed ITP “within 24 hours after [flu]

vaccination,” and this “timing of onset is faster than immune system activation and platelet clearance would allow” and “is not supported by the proposed mechanism.” Resp. Ex. C at 6, 8; see also Resp. Ex. A at 9 (“This timing is shorter than would be expected for an association between antibody production after vaccination and development of ITP.”).

While Petitioner testified that she had received prior flu vaccinations, Dr. Baumann opined that she did not know the flu strains in the prior vaccinations. Tr. 320. Dr. Baumann testified that it depends on what flu vaccines she had previously received, and the strains in those vaccines. 77 Id. “[I]f the same strains were [received] and [] an autoantibody was produced from that specific strain, [the timing] still would be three days” for a secondary exposure. Id.

Dr. Baumann testified that symptoms like petechiae generally “take[] days, if not longer”

to manifest. Tr. 321. Thus, she disagreed with Dr. Ghose’s assertion that Petitioner’s platelet decrease within one to two days of vaccination “confirm[ed] the immune mediated nature of the disease that characterizes ITP.” Resp. Ex. A at 8 (quoting Pet. Ex. 10 at 6).

In her first report, she explained the events that occur in order for petechiae to develop in ITP:

[A]utoantibodies to platelets are produced, platelets are cleared from the blood stream, and spontaneous bleeding into the skin occurs from damage to the blood vessels. When the body is exposed to an inactivated vaccine such as the [flu] vaccine, the virus is phagocytosed by dendritic cells. Antigen fragments are presented on the cell surface of the dendritic cell. TH2-cells and B-cells will

77 This information was not provided.

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become activated upon binding to the dendritic cell. The activated TH2 cell produces cytokines which allow B-cells to differentiate and proliferate. B-cells then produce antibodies against the foreign antigen (i.e. [flu]). This process takes 10-14 days.

Resp. Ex. A at 8; see also Resp. Ex. C at 5 (“For symptoms of ITP to occur, the immune system is activated against platelets, platelets need to be cleared from the system, and petechia need to form by breaking small blood vessels.”). Therefore, Petitioner’s timing of less than 24 hours after vaccination “is shorter than would be expected for an association between antibody production after vaccination and development of ITP.” Resp. Ex. A at 9.

Overall, Dr. Baumann concluded “the timing is insufficient for the purported mechanism and does not reliably explain how a six-day episode of ITP [from] October 17, 2019[] to October 23, 2019 could result in alleged persistent fatigue in the absence of any other evidence of ITP.” Resp. Ex. C at 7.

4. Respondent’s Expert, Dr. You-Wen He 78

a. Background and Qualifications

Dr. He is currently a Professor of Integrated Immunobiology at Duke University Medical Center. Resp. Ex. G at 1. Dr. He received his M.D. from the Fourth Military Medical University in Xian, China and his Ph.D. in Microbiology and Immunology from the University of Miami School of Medicine in Miami, Florida. Id. His research areas include “innate and adaptive immunity against viral and bacterial infections, as well as tumors.” Resp. Ex. D at 1. He has conducted research on human immune responses to viral infections and is currently a Co- Principal Investigator for clinical trials focusing on cancer immunotherapy. Id. Dr. He has reviewed National Institutes of Health studies, served on editorial boards, and has authored or co-authored numerous publications. Id. at 1-2; Resp. Ex. G at 2-3, 7-17.

Dr. He is not a hematologist. Tr. 211. He does not have experience treating ITP patients.

Tr. 211, 259. He does not treat patients in the United States, but does see patients in his home country of China. Tr. 211. Dr. He has not published on ITP, nor has his research focused on ITP or platelets. Tr. 259. Dr. He was admitted as an expert in immunology, without objection, with his testimony focusing on the theory presented and related research. Tr. 211-12.

b. Opinion

Dr. He opined “to a reasonable degree of medical certainty[,] that there is no reliable evidence to support [Petitioner’s] theory that the [flu] vaccine caused [Petitioner’s] ITP.” Resp. Ex. D at 26; see also Resp. Ex. F at 21-22.

78 Dr. He provided two expert reports and testified at the entitlement hearing. Resp. Exs. D, F; Tr. 149, 272.

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i. Althen Prong One

Dr. He opined the flu vaccine cannot cause ITP and there is no evidence to support a causal link between flu vaccination and ITP. Tr. 259; Resp. Ex. at 4.

He explained the innate immune system is the “first line of defense” and acts as a signal to activate an adaptive immune response, which provides protection from the antigen/stimulus. Tr. 215; see also Resp. Ex. F8 at 1. 79 During an innate immune response, various cells are involved and over the course of approximately three days, these cells are activated and send signals to the T and B lymphocytes to activate the adaptive immune response, which provides a host’s immune system with “memory” to enable a more rapid and efficient immune response upon subsequent exposures. Tr. 215-18; see also Resp. Ex. F8 at 1-2, 4. Thus, with an adaptive immune response, there is a lag time between antigen exposure and response, which typically takes five to 10 days. Resp. Ex. F at 14; see also Resp. Ex. F8 at 1. This timing is faster with a memory response (i.e., a response to a previously encountered stimulus) than a primary response (i.e., a response to a newly encountered stimulus). Tr. 218; Resp. Ex. F at 14-15 (“The time for antigen-specific B cells to be activated and become antibody secreting cells [] upon primary vaccination takes 8-10 days while the time for secondary vaccination takes 5-7 days.”).

Although “[t]he pathogenesis of primary ITP remains to be fully understood,” Dr. He opined both the innate and adaptive immune responses are involved. Resp. Ex. D at 3; see also Resp. Ex. F at 13-14, 21-22; Tr. 213. Dr. He found no literature or evidence showing that any cells involved in the innate immune response destroy platelets. Tr. 216-17; Resp. Ex. F at 13. Dr. He testified that from his review of the literature, it is “very clear” that ITP is an adaptive immune-mediated response. Tr. 213; see also Resp. Ex. F at 13-14.

He explained that “[t]he predominant cause of thrombocytopenia is due to reduced platelet lifespan caused by autoimmune reactions including autoantibodies and autoreactive cytotoxic T cells against platelets as well as humoral and cellular autoimmunity against megakaryocytes.” Resp. Ex. D at 3 (citing Resp. Ex. D1 at 1, 4). 80 The autoantibodies targeting

79 Jean S. Marshall et al., An Introduction to Immunology and Immunopathology, 14 Allergy Asthma Clin. Immunol. 5 (2018). 80 Donald M. Arnold & Adam Cuker, Immune Thrombocytopenia (ITP) in Adults: Clinical Manifestations and Diagnosis, UpToDate, https://www.uptodate.com/contents/immunethrombocytopenia -itp-in-adults-clinical-manifestations-and-diagnosis (last updated July 5, 2023). An updated version (last updated July 26, 2023) was filed as Resp. Ex. F6.

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platelets or platelet antigens destroy circulating platelets “through Fc-mediated phagocytosis[81] in the spleen and other reticuloendothelial tissues,” leading to reduced platelet production. Id. (citing Resp. Ex. D2 at 2). 82 He added that cytotoxic T cells may have a direct lytic effect. Id. (citing Resp. Ex. D2 at 2). Thus, because “the pathogenesis of ITP is mediated by anti-platelet autoantibodies and autoreactive antigen specific cytotoxic T cells,” both the innate immune system and the adaptive immune systems are at play. Id. at 9; see also Tr. 213; Resp. Ex. F8 (providing an overview of innate and adaptive immunity).

Dr. He next addressed the literature, opining there is no evidence causally linking the flu vaccine to ITP. Resp. Ex. D at 3, 26. For support, he cited a vaccine safety review from Dudley et al. 83 that used data compiled in the 2012 Institute of Medicine (“IOM”) Report and the 2014 Agency for Healthcare Research and Quality (“AHRQ”) Report to assess causal associations of adverse events post-vaccination. Resp. Ex. D3 at 1 (citing Resp. Ex. D7; 84 Resp. Ex. D8; 85 Resp. Ex. D9). 86 Dr. He noted that the study did not identify an association between the flu vaccine and ITP. Resp. Ex. D at 4 (citing Resp. Ex. D3 at 4, 4 tbl. 1). However, Dudley et al. acknowledged that the 2012 IOM Report and the AHRQ Report did not assess a relationship between ITP and flu vaccination. See Resp. Ex. D3 at 7 (“The IOM report only assessed the

81 Fc receptors are “specific cell-surface receptors for antigen-antibody complexes or aggregated immunoglobulins that bind a site in the Fc portion of the immunoglobulin molecule and may exhibit specificity for particular immunoglobulin classes. Fc receptors are found on B cells, K cells, macrophages, neutrophils, and eosinophils, and, during some developmental stages, on T cells; those on K cells, macrophages, and neutrophils bind to opsonizing antibodies bound to antigens and trigger phagocytosis of the antigen.” Fc Receptors, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=102550 (last visited June 17, 2026). Phagocytosis refers to the internalization or endocytosis of particulate matter, such as microorganisms or cell fragments, and results in the material being engulfed and killed. Phagocytosis, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/ dorland/definition?id=38307 (last visited June 17, 2026); Glossary, supra note 55. 82 Syed Mahamad et al., Proceedings of the Immune Thrombocytopenia Summit: New Concepts in Mechanisms, Diagnosis, and Management, 7 Res. Pract. Thromb. Haemost. 1 (2023). 83 Matthew Z. Dudley et al., The Safety of Vaccine Safety Science: Systematic Reviews of the Evidence, 20 Lancet Infect. Dis. e80 (2020). 84 Inst. of Med., Adverse Effects of Vaccines: Evidence and Causality (Kathleen Stratton et al. eds., 2012). 85 Margaret A. Maglione et al., Safety of Vaccines Used for Routine Immunization of US Children: A Systematic Review, 134 Pediatrics 325 (2014). 86 Agency for Healthcare Rsch. & Quality, Safety of Vaccines Used for Routine Immunization in the United States (Apr. 6, 2020), https://effectivehealthcare.ahrq.gov/products/safety- vaccines/protocol. The 2014 version was cited in Dr. He’s report; however, the 2020 research protocol version was filed in this case.

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relationship between [ITP] and tetanus, diphtheria, or pertussis containing vaccines, and the AHRQ report concluded that [strength of evidence] was moderate for an association between MMR vaccine and [ITP]. Our Review has concluded that the MMR vaccine can very rarely cause [ITP] in children.”). And thus, Dr. He’s reliance on this literature appears misplaced.

Dr. He next cited an updated report from AHRQ published in May 2021. Resp. Ex. D4. 87 Based on additional evidence, the study found no evidence of an increased risk of ITP with flu vaccination. Id. at 16 tbl. A. Dr. He, like Dr. Baumann, also relied upon Grimaldi-Bensouda et al. and Lafaurie et al., and neither study found an association between flu vaccination and ITP. Resp. Ex. D at 4 (citing Resp. Exs. A9, C1).

Overall, he opined that “these systemic studies have concluded that there is no evidence to link [flu] vaccine with ITP development,” and given the large numbers of flu vaccinations administered each year, “the lack of any reliable evidence to associate [flu] vaccine with ITP strongly indicates that the [flu] vaccine more likely than not does not cause ITP.” Resp. Ex. D at 4.

Next, Dr. He addressed aspects of Petitioner’s experts’ reports. First, as to Dr. Ghose’s proposed theory of molecular mimicry, Dr. He opined there were insufficient details to support the theory. Resp. Ex. D at 9; Tr. 229-30. Dr. He explained Dr. Ghose did not provide homology between the flu vaccine and platelets, and Dr. He is not aware of any relevant homology between the two. Tr. 230. Dr. He also noted that sequence homology alone cannot cause ITP. Resp. Ex. F at 21.

With regard to Dr. Ghose’s literature, he disagreed that it showed an association between the flu vaccine and ITP. Resp. Ex. D at 5-8. Dr. He criticized Dr. Ghose’s literature references as “completely lacking in reliable scientific strength.” Id. at 5. As to the case reports specifically, Dr. He opined the case reports (1) show “a simple temporal relationship” that is insufficient for causation; (2) span more than 30 years, despite the regularity of the administration of the flu vaccine, and thus “it cannot be reliably concluded that the [flu] vaccine was more likely than not the cause;” and (3) do no support an onset of one day or less, and instead report onset intervals between four days and five weeks. Id. at 6, 8-9; see also Tr. 265. Some of Dr. Ghose’s literature also focused on infections or vaccines other than the flu vaccine, or they were factually different from this case. Resp. Ex. D at 8.

Dr. He also addressed Dr. Akbari’s proposed theory and literature. 88 Overall, Dr. He opined Dr. Akbari “only provided scientific studies reporting activation of inflammasome pathway, cytokine production[,] and Th17 differentiation upon [flu] vaccination,” which are part of a normal immune response, and failed to provide evidence that the flu vaccine “could have

87 Agency for Healthcare Rsch. & Quality, Safety of Vaccines Used for Routine Immunization in the United States: An Update (May 25, 2021), https://effectivehealthcare.ahrq.gov/products/ safety-vaccines/research. 88 For some of Dr. He’s criticisms of Dr. Akbari’s literature, see Resp. Ex. D at 13-16; Resp. Ex. F at 2-3, 5-8, 11-12.

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induced strong immune responses to break the host immune tolerance mechanisms to cause ITP in [Petitioner].” Resp. Ex. F at 21.

Dr. He agreed with Dr. Akbari that the flu vaccine activates inflammasomes within hours, which is step one of his theory. Tr. 340 (citing Pet. Ex. 155); see also Resp. Ex. D at 13 (“[I]t is entirely expected that both [flu] virus infection and [flu] vaccinations will activate the inflammasomes and produce inflammatory cytokines including IL-1β. Without proper activation of the innate immunity, vaccines will not work as intended to induce adaptive immunity.”); Resp. Ex. F at 2-4; Tr. 244 (agreeing with Dr. Akbari that inflammasomes are part of the innate immune systems and be activated “very quickly”). But Dr. He added that “[i]nflammasome itself is not going to be able to attack platelets.” Tr. 243.

Part two of this process involves the activation of antigen presenting cells by inflammasomes, which Dr. Akbari testified could occur within hours. Tr. 340-41. Dr. He agreed that IL-1β “could affect homeostasis” but opined it would “take days,” and not be as rapid as Dr. Akbari posited. Tr. 341-42. Additionally, Dr. He noted there is no evidence that IL-1β kills platelets directly. Tr. 341, 344; see also Resp. Ex. D at 13. And because of this, to affect homeostasis, other cells would have to help facilitate the destruction of the platelets, which would take “at least more than three days” and would “never[] [be] within 24 hours.” Tr. 342- 43. Thus, Dr. He opined there is no evidence to support ITP can be caused by immediate reactions mediated through the innate immune system like Dr. Akbari asserted, or that inflammasomes, cytokines, and other innate immune cells play a direct role in ITP. Resp. Ex. D at 11, 13-14; Resp. Ex. F at 6-11; see also Tr. 235-37, 247-48.

As to step three (activation of autoreactive B cells), Dr. He testified that IL-1β, other cytokines, or antigen-presenting cells activate autoreactive B cells and conventional naïve B cells. Tr. 343. However, “it will never happen within one day or two days.” Id. Autoreactive B cells, like memory B cells, have a lower threshold, leading to a faster response; however, this only speeds up the process by two to three days, and never to the point of one day or less. Tr. 231-32, 343-44. Thus, he explained autoreactive B cells cannot produce antibody, bind to platelets, and cause destruction within one day. Tr. 231-32, 344-45.

On cross-examination, Dr. He agreed B cells produce IgM antibodies and that IgM and IgG antibodies can cause platelet destruction. Tr. 262-63. However, it would take “at least [] three days,” according to Dr. He, for these antibodies to be detected after vaccination. Id. He maintained IgM, which is produced before IgG, 89 cannot peak within one to two days. Tr. 263.

In response to molecular mimicry, Dr. He took issue with the fact that Dr. Akbari did not provide any details on any alleged amino acid sequence similarity between flu vaccine antigens

89 “IgM antibodies are produced as a body’s first response to a new infection, and increase for several weeks and then decline as IgG production begins. IgG antibodies are produced during an initial infection or other antigen exposure, rising a few weeks after it begins, then decreasing and stabilizing.” Blender v. Sec’y of Health & Hum. Servs., No. 16-1308V, 2021 WL 1096662, at *4 n.13 (Fed. Cl. Spec. Mstr. Feb. 26, 2021) (internal quotation marks and citation omitted).

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and platelet proteins. Resp. Ex. D at 18, 22. He opined that molecular mimicry requires either structural or sequence homology. Tr. 264-65.

Overall, Dr. He opined that although “inflammasome activation is an essential part of host innate immune activation[,] Dr. Akbari did not substantiate how inflammasome activation would have caused ITP.” Resp. Ex. D at 22; see also Tr. 255 (testifying that he has not seen evidence of a connection between activation of inflammasome and destruction of platelets). “Dr. Akbari also hypothesized molecular mimic theory without providing any molecular details, either amino acid sequence homology or structural homology, between [flu] vaccine and platelet.” Resp. Ex. D at 22. Dr. He maintained ITP is not mediated by the innate immune system alone, and requires the adaptive immune system. Id. at 23; Resp. Ex. F at 13.

ii. Althen Prongs Two and Three

Dr. He summarized Petitioner’s clinical course: “[Petitioner] received a[] [flu] vaccine on October 16, 2019 and felt shaky and cold at about [one] hour after the vaccination. She had a platelet count of [five] on October 17, 2019 and [was diagnosed with and treated for] ITP. Her platelet count returned to normal level shortly after treatment.” Resp. Ex. D at 3; see also Tr. 227-28. Dr. He opined “the timing between receipt of the vaccine and development of ITP in [Petitioner] is not consistent with the cause and effect of immunizations with flu vaccine and the subsequent development of ITP.” Resp. Ex. D at 24.

Dr. He disagreed with Dr. Ghose’s assertion that Petitioner’s ITP was “[u]ndoubtedly”

due to her flu vaccination as well as Dr. Ghose’s assertion that a rapid platelet drop as seen in Petitioner “confirms the immune mediated nature” of ITP as neither are consistent with the evidence in this case nor immunology. Resp. Ex. D at 7 (quoting Pet. Ex. 10 at 6-7). He testified that no immunological process can explain how Petitioner’s clinical course led to ITP within 24 hours of vaccination. Tr. 229.

Dr. He opined none of the literature supports a time frame consistent with the one day onset seen in Petitioner. Resp. Ex. D at 6, 8-9. Further, the rapid onset directly counters immunologic principles. Id. at 9, 22-23. Dr. He explained

[t]he timeframe for innate immunity to activate and play its function is within the first 3-5 days after vaccination while the adaptive immunity is not fully activated until day 7-10 after infection or vaccination. The adaptive immune response then undergoes contraction to form a stable memory pool by day 25. As the pathogenesis of ITP is mediated by anti-platelet autoantibodies and autoreactive antigen-specific cytotoxic T cells, both essential components of the host adaptive immune responses, the claim that [Petitioner’s] ITP is due to [flu] vaccination induced adaptive immune responses cannot stand. It is simply impossible for the adaptive immune system to produce anti-platelet autoantibodies or autoreactive cytotoxic T lymphocytes within [one]-day upon [flu] vaccination.

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Id. at 9 (citing Resp. Ex. D10 at 2 fig. 1); 90 see also Tr. 215; Resp. Ex. F at 13-15. Thus, he concluded that a one-day onset is not characteristic of ITP “and certainly argues against any causal relationship to the vaccine.” Resp. Ex. D at 10, 26; see also Tr. 214 (testifying that it is “impossible to activate the adaptive immune system” within one day); Resp. Ex. F at 14-15 (“[I]t is impossible for T and B cells to be activated within [one] day upon [flu] vaccination to cause [Petitioner’s] ITP.”).

For further support, Dr. He referenced a graph from Carter et al. 91 to show the timeline of antigen-specific antibodies after exposure to infection and primary and secondary vaccination:

Resp. Ex. F at 15 (citing Resp. Ex. F10 at 9 fig. 2); see also Tr. 219-21 (discussing this chart). He testified that this chart shows the time it takes for the production of antigen-specific antibodies. Tr. 222. He opined there is no evidence as illustrated by this chart to indicate an adaptive immune response could occur within one day. Tr. 221; see also Resp. Ex. F at 21-22. And even with a memory response, an adaptive immune response cannot be shortened to one day. Tr. 225.

Therefore, because ITP involves the adaptive immune system, which requires a minimum of five days to be mounted, “[i]t is impossible for adaptive immunity to be induced in one day by [flu] vaccination to cause ITP.” Resp. Ex. F at 21-22.

90 Matthew A. Williams & Michael J. Bevan, Effector and Memory CTL Differentiation, 25 Annu. Rev. Immunol. 171 (2007). 91 Michael J. Carter et al., The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications, 8 Front. Immunol. 1 (2017).

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III. DISCUSSION

A. Standards for Adjudication

The Vaccine Act was established to compensate vaccine-related injuries and deaths. § 10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as a simple, fair and expeditious means for compensating vaccine-related injured persons. The Program was established to award ‘vaccine-injured persons quickly, easily, and with certainty and generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting H.R. Rep. No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).

Petitioner’s burden of proof is by a preponderance of the evidence. § 13(a)(1). The preponderance standard requires a petitioner to demonstrate that it is more likely than not that the vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health & Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). Petitioner need not make a specific type of evidentiary showing, i.e., “epidemiologic studies, rechallenge, the presence of pathological markers or genetic predisposition, or general acceptance in the scientific or medical communities to establish a logical sequence of cause and effect.” Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006). Instead, Petitioner may satisfy her burden by presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.

In particular, Petitioner must prove that the vaccine was “not only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Hum. Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)); see also Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). The received vaccine, however, need not be the predominant cause of the injury. Shyface, 165 F.3d at 1351. A petitioner who satisfies this burden is entitled to compensation unless Respondent can prove, by a preponderance of the evidence, that the vaccinee’s injury is “due to factors unrelated to the administration of the vaccine.” § 13(a)(1)(B). However, if a petitioner fails to establish a prima facie case, the burden does not shift. Bradley v. Sec’y of Health & Hum. Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

“Regardless of whether the burden ever shifts to the [R]espondent, the special master may consider the evidence presented by the [R]espondent in determining whether the [P]etitioner has established a prima facie case.” Flores v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 157, 162-63 (2014); see also Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir. 2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted to offer evidence to demonstrate the inadequacy of the [P]etitioner’s evidence on a requisite element of the [P]etitioner’s case-in-chief.”); Pafford, 451 F.3d at 1358-59 (“[T]he presence of multiple potential causative agents makes it difficult to attribute ‘but for’ causation to the vaccination. . . . [T]he Special Master properly introduced the presence of the other unrelated contemporaneous events as just as likely to have been the triggering event as the vaccinations.”).

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B. Factual Issues

A petitioner must prove, by a preponderance of the evidence, the factual circumstances surrounding her claim. § 13(a)(1)(A). To resolve factual issues, the special master must weigh the evidence presented, which may include contemporaneous medical records and testimony. See Burns v. Sec’y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (explaining that a special master must decide what weight to give evidence including oral testimony and contemporaneous medical records). Contemporaneous medical records, “in general, warrant consideration as trustworthy evidence.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). But see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378, 1382 (Fed. Cir. 2021) (rejecting the presumption that “medical records are accurate and complete as to all the patient’s physical conditions”); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed. Cl. 532, 538 (2011) (“[T]he absence of a reference to a condition or circumstance is much less significant than a reference which negates the existence of the condition or circumstance.” (quoting Murphy v. Sec’y of Health & Hum. Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam, 968 F.2d 1226 (Fed. Cir. 1992))), recons. den’d after remand, 105 Fed. Cl. 353 (2012), aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013).

There are situations in which compelling testimony may be more persuasive than written records, such as where records are deemed to be incomplete or inaccurate. Campbell v. Sec’y of Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006) (“[L]ike any norm based upon common sense and experience, this rule should not be treated as an absolute and must yield where the factual predicates for its application are weak or lacking.”); Lowrie v. Sec’y of Health & Hum. Servs., No. 03-1585V, 2005 WL 6117475, at *19 (Fed. Cl. Spec. Mstr. Dec. 12, 2005) (“[W]ritten records which are, themselves, inconsistent, should be accorded less deference than those which are internally consistent.” (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a determination regarding a witness’s credibility is needed when determining the weight that such testimony should be afforded. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379 (Fed. Cir. 2009); Bradley, 991 F.2d at 1575.

Despite the weight afforded to medical records, special masters are not rigidly bound by those records in determining onset of a petitioner’s symptoms. Valenzuela v. Sec’y of Health & Hum. Servs., No. 90-1002V, 1991 WL 182241, at *3 (Fed. Cl. Spec. Mstr. Aug. 30, 1991); see also Eng v. Sec’y of Health & Hum. Servs., No. 90-1754V, 1994 WL 67704, at *3 (Fed. Cl. Spec. Mstr. Feb. 18, 1994) (noting Section 13(b)(2) “must be construed so as to give effect also to § 13(b)(1) which directs the special master or court to consider the medical records (reports, diagnosis, conclusions, medical judgment, test reports, etc.), but does not require the special master or court to be bound by them”).

C. Causation

To receive compensation through the Program, Petitioner must prove either (1) that she suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—corresponding to a vaccine that she received, or (2) that she suffered an injury that was actually caused by a vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319-20. Petitioner must

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show that the vaccine was “not only a but-for cause of the injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface, 165 F.3d at 1352-53).

Because Petitioner does not allege she suffered a Table Injury, she must prove a vaccine she received caused her injury. To do so, Petitioner must establish, by preponderant evidence: “(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d at 1278.

The causation theory must relate to the injury alleged. Petitioner must provide a sound and reliable medical or scientific explanation that pertains specifically to this case, although the explanation need only be “legally probable, not medically or scientifically certain.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d. 543, 548-49 (Fed. Cir. 1994). Petitioner cannot establish entitlement to compensation based solely on her assertions; rather, a vaccine claim must be supported either by medical records or by the opinion of a medical doctor. § 13(a)(1). In determining whether a petitioner is entitled to compensation, the special master shall consider all material in the record, including “any . . . conclusion, [or] medical judgment . . . which is contained in the record regarding . . . causation.” § 13(b)(1)(A). The undersigned must weigh the submitted evidence and the testimony of the parties’ proffered experts and rule in Petitioner’s favor when the evidence weighs in her favor. See Moberly, 592 F.3d at 1325-26 (“Finders of fact are entitled—indeed, expected—to make determinations as to the reliability of the evidence presented to them and, if appropriate, as to the credibility of the persons presenting that evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in Petitioner’s favor).

Testimony that merely expresses the possibility—not the probability—is insufficient, by itself, to substantiate a claim that such an injury occurred. See Waterman v. Sec’y of Health & Hum. Servs., 123 Fed. Cl. 564, 573-74 (2015) (denying Petitioner’s motion for review and noting that a possible causal link was not sufficient to meet the preponderance standard). The Federal Circuit has made clear that the mere possibility of a link between a vaccination and a petitioner’s injury is not sufficient to satisfy the preponderance standard. Moberly, 592 F.3d at 1322 (emphasizing that “proof of a ‘plausible’ or ‘possible’ causal link between the vaccine and the injury” does not equate to proof of causation by a preponderance of the evidence); Boatmon v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019). While certainty is by no means required, a possible mechanism does not rise to the level of preponderance. Moberly, 592 F.3d at 1322; see also de Bazan, 539 F.3d at 1351.

IV. SEVERITY REQUIREMENT ANALYSIS

To receive compensation, Petitioner must show that she

(i) suffered the residual effects or complications of [her] illness, disability, injury, or condition for more than six months after the administration of the vaccine, or (ii) died from the administration of the vaccine, or (iii) suffered such illness, disability, injury, or condition from the vaccine which resulted in inpatient hospitalization and surgical intervention.

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§ 11(c)(1)(D).

Compensation is not available under the Vaccine Act for minor illness which are shortlived . Wright v. Sec’y of Health & Hum. Servs., 22 F.4th 999, 1001-04 (Fed. Cir. 2022). Cases may appropriately be dismissed for failure to substantiate the severity requirement. See, e.g., Hinnefeld v. Sec’y of Health & Hum. Servs., No. 11-328V, 2012 WL 1608839, at *4-5 (Fed. Cl. Spec. Mstr. Mar. 30, 2012) (dismissing case where medical history revealed that petitioner’s GBS resolved less than two months after onset). It is Petitioner’s burden to prove her case, including the six-month requirement, by a preponderance of the evidence. See § 13(a)(1)(A). To satisfy the six-month requirement, “[a] potential petitioner must do something more than merely submit a petition and an affidavit parroting the words of the statute.” Faup v. Sec’y of Health & Hum. Servs., No. 12-87V, 2015 WL 443802, at *3 (quoting Black v. Sec’y of Health & Hum. Servs., 33 Fed. Cl. 546, 550 (1995), aff’d, 93 F.3d 784, 792 (Fed. Cir. 1996)). A petitioner cannot establish the length or ongoing nature of an injury merely through their own statements, but rather is required to “submit supporting documentation which reasonably demonstrates that the alleged injury or its sequelae lasted more than six months.” Black, 33 Fed. Cl. at 550; see also Lett v. Sec’y of Health & Hum. Servs., 39 Fed. Cl. 259, 260-61 (1997) (“Section 300aa- 13(a)(1) provides that a special master may not award compensation ‘based on the claims of [a] petitioner alone, unsubstantiated by medical records or by medical opinion.’”).

The Federal Circuit recently addressed the six-month severity requirement in Wright. 22 F.4th at 1001. The petitioner’s child suffered ITP, a condition characterized by abnormally low platelet counts, bruising, and bleeding, after receipt of the MMR vaccination. Id. The child’s ITP resolved in less than three months, and although he had later episodes of bruising, testing showed that his platelet count remained normal. Id. at 1003-04. The Circuit held that the petitioner failed to satisfy the six-month requirement when the platelet count normalized less than three months post-ITP onset because “relatively non-invasive ongoing [platelet] monitoring” was not a “residual effect” pursuant to § 11(c)(1)(D)(i). Id. at 1001, 1003, 1006-07. The Circuit noted that the child’s later bruising was not related to his vaccine injury and that ongoing testing “did not reveal, constitute, or cause any somatic change.” Id. at 1001.

Defining the language in § 11(c)(1)(D)(i), the Circuit ruled that “[t]he term ‘residual effects’ . . . requires a change within the patient that is caused by the vaccine injury.” Wright, 22 F.4th at 1004. It continued, stating that “‘[r]esidual’ suggests something remaining or left behind from a vaccine injury . . . . Because vaccine injuries are somatic conditions defined by their signs and symptoms within the patient, . . . their residues are similarly defined.” Id. at 1005-06 (internal citations omitted). Further, the words “suffered” and “complication” in association with “residual effects” in § 11(c)(1)(D)(i) “suggest that Congress contemplated residual effects to be detrimental conditions within the patient, such as lingering or recurring signs and symptoms.” Id. at 1006. The Circuit concluded that “[r]ead together, ‘residual effects’ and ‘complications’ appear to both refer to conditions within the patient, with ‘residual effects’ focused on lingering signs, symptoms, or sequelae characteristic of the course of the original vaccine injury, and ‘complications’ encompassing conditions that may not be ‘essential part[s] of the disease’ or may be outside the ordinary progression of the vaccine injury.” Id.

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Considering and weighing all of the evidence, the undersigned finds it preponderates in favor of a finding that Petitioner “suffered the residual effects or complications of [her] [ITP] for more than six months after the administration of the vaccine.” § 11(c)(1)(D)(i).

Petitioner received the flu vaccine at issue on October 16, 2019 and her onset manifested within one day, by October 17. Thus, to satisfy the six-month severity requirement, Petitioner would have to provide preponderant evidence that she suffered from the residual effects of her ITP until mid-April 2020. To satisfy the severity requirement, Petitioner contends she suffered from ITP-related fatigue for more than six months.

First, the undersigned notes the experts agree that fatigue can be associated with ITP and the literature supports the finding that fatigue is a residual effect of ITP.

Second, the undersigned finds there is evidence to support a finding that Petitioner experienced fatigue past mid-April 2020. Here, Petitioner provided evidence that she was suffering from fatigue until at least May 2020, as evidenced by her email to her attorney. Specifically, Petitioner wrote on May 27, 2020 that her platelets were above 370,000 K/uL but that she was “still tired at times but otherwise [she was] doing ok.” Pet. Ex. 6 at 1. The undersigned finds this is not negated by a lack of reference of fatigue in Dr. Dammrich’s records during this time. See Shapiro, 101 Fed. Cl. at 538 (“[T]he absence of a reference to a condition or circumstance is much less significant than a reference which negates the existence of the condition or circumstance.” (quoting Murphy, 23 Cl. Ct. at 733, aff’d per curiam, 968 F.2d 1226 (Fed. Cir. 1992))), recons. den’d after remand, 105 Fed. Cl. 353 (2012), aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013).

Third, the undersigned finds Respondent’s arguments for why Petitioner’s fatigue was not due to her ITP not persuasive.

Respondent argues that Petitioner’s fatigue was due to other reasons, including Covid and her sister’s death in April 2020. However, this would not explain ongoing fatigue which began after vaccination and was still present in April 2020. Moreover, in her email to her attorney, Petitioner is referencing her ITP, and notes she was “still tired at times but otherwise [she was] doing ok.” Pet. Ex. 6 at 1. The reasonable inference is that she attributes her fatigue to her prior ITP. Respondent’s assertions that Petitioner’s fatigue was due to Covid or her sister’s death is not supported by any evidence. Because “close calls” are resolved in Petitioner’s favor, and Respondent failed to provide evidence that Petitioner’s ITP was not the reason for her fatigue, the undersigned does not find Respondent’s argument persuasive. Althen, 418 F.3d at 1280.

Respondent also argues that fatigue is a residual effect in only those ITP patients with chronic and active ITP (as evidence by low platelets), not patients like Petitioner, whose platelet levels had normalized. However, Respondent did not cite to an article supporting this narrow finding. Overall, the literature shows ITP patients complain of fatigue, which can be associated but is not always correlated with platelet levels. See, e.g., Pet. Ex. 63 at 2 (noting “[i]t is less clear whether fatigue is associated with disease severity as measured by the platelet count” and summarized studies that have found fatigue did and did not correlate to platelet count); Pet. Ex.

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153 at 5 (finding “fatigue scores did not correlate with the most recent platelet counts at baseline”).

In conclusion, the undersigned finds that Petitioner did experience fatigue, which was a residual effect of her ITP, for longer than six months. Therefore, she does meet the severity requirement set forth in the Vaccine Act. However, as discussed below, Petitioner has not satisfied all three Althen prongs.

V. CAUSATION ANALYSIS

A. Althen Prong One

Under Althen prong one, Petitioner must set forth a medical theory explaining how the received vaccine could have caused the sustained injury. Andreu, 569 F.3d at 1375; Pafford, 451 F.3d at 1355-56. Petitioner’s theory of causation need not be medically or scientifically certain, but it must be informed by a “sound and reliable” medical or scientific explanation. Boatmon, 941 F.3d at 1359; see also Knudsen, 35 F.3d at 548; Veryzer v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 214, 223 (2011) (noting that special masters are bound by both § 13(b)(1) and Vaccine Rule 8(b)(1) to consider only evidence that is both “relevant” and “reliable”). If Petitioner relies upon a medical opinion to support her theory, the basis for the opinion and the reliability of that basis must be considered in the determination of how much weight to afford the offered opinion. See Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (“The special master’s decision often times is based on the credibility of the experts and the relative persuasiveness of their competing theories.”); Perreira v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (stating that an “expert opinion is no better than the soundness of the reasons supporting it” (citing Fehrs v. United States, 620 F.2d 255, 265 (Ct. Cl. 1980))).

In her pre-hearing brief, Petitioner contends she presented evidence of a “biologically plausible mechanism” 92 which “is based on molecular mimicry.” 93 Pet. Pre-Hearing Br., filed Jan. 7, 2025, at 6-9 (ECF No. 70) (“Here, Petitioner has presented a biologically plausible theory to explain how the [flu] vaccination provoked an autoimmune response which caused ITP by molecular mimicry.”). Petitioner’s post-hearing brief maintains Petitioner presented a “sound

92 Petitioner’s theory must be “sound and reliable.” Boatmon, 941 F.3d at 1359. “[P]etitioner must do more than demonstrate a ‘plausible’ or ‘possible’ causal link between the vaccination and the injury; [s]he must prove [her] case by a preponderance of the evidence.” W.C. v. Sec’y of Health & Hum. Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013). 93 “Molecular mimicry is sequence and/or conformational homology between an exogenous agent (foreign antigen) and self-antigen leading to the development of tissue damage and clinical disease from antibodies and T cells directed initially against the exogenous agent that also react against self-antigen.” Resp. Ex. D7 at 99. Dr. Akbari agreed molecular mimicry is part of the adaptive immune system. See, e.g., Pet. Ex. 88 at 16 (explaining “B cells, part of the adaptive immune system, produce antibodies that mistakenly target the body’s own tissues, leading to adverse outcomes”).

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and reliable medical theory in which the flu vaccine can cause ITP . . . based on molecular mimicry.” Pet. Post-Hearing Br. at 8-11. 94

The experts all appear to agree that the adaptive immune system is responsible for causing platelet destruction. Dr. He explained that ITP is thought to be caused by autoimmune reactions including autoantibodies and autoreactive cytotoxic T cells against platelets, as well as humoral and cellular autoimmunity against megakaryocytes. The autoantibodies targeting platelets or platelet antigens destroy circulating platelets and cause reduced platelet production. Because ITP is mediated by anti-platelet autoantibodies and autoreactive antigen specific cytotoxic T cells, both the innate immune system and the adaptive immune systems play a role in the pathogenesis of ITP.

Dr. Akbari’s expert reports and testimony was more difficult to follow. He appears to suggest a combination of theories, implicating a type of hypersensitivity/inflammasome reaction and molecular mimicry, which he opines involves both the innate and adaptive immune systems.

Therefore, consistent with both parties’ experts, the undersigned finds that both the innate and adaptive immune systems play a role in the pathogenesis of ITP.

Assuming Petitioner has proven a sound and reliable causal mechanism under Althen prong one, the undersigned finds Petitioner did not provide preponderant evidence of a logical sequence of cause and effect or a proximate temporal relationship between the flu vaccination and Petitioner’s ITP. Due to the facts and circumstances of this case, specifically the fact that Petitioner developed symptoms within one day after receipt of a flu vaccine, the undersigned’s determination as to causation turns on an analysis of Althen prongs two and three, and thus, the undersigned focuses on Althen prongs two and three. See Vaughan ex rel. A.H. v. Sec’y of Health & Hum. Servs., 107 Fed. Cl. 212, 221-22 (2012) (finding the special master’s failure to rule on Althen prong one not fatal to his decision because Althen prong two was fatal to Petitioner’s case); Hibbard v. Sec’y of Health & Hum. Servs., 698 F.3d 1355, 1364 (Fed. Cir. 2012) (“discern[ing] no error in the manner in which the special master chose to address the Althen [prongs]” when he focused on Althen prong two after “assuming the medical viability of [the] theory of causation”).

While the undersigned is not making a finding as to whether Petitioner has provided preponderant evidence of Althen prong one, a one-day onset is not compatible with a theory based on the finding that ITP is caused by the innate and adaptive immune systems. This is because, as explained by Dr. He, the pathogenesis involves autoimmune reactions including autoantibodies and autoreactive cytotoxic T cells against platelets, as well as humoral and cellular autoimmunity against megakaryocytes. The autoantibodies targeting platelets or platelet antigens destroy circulating platelets and cause reduced platelet production.

94 Petitioner described her theory as both “sound and reliable” and “biologically plausible” in her post-hearing brief. Pet. Post-Hearing Br. at 8, 11.

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Again, as explained by Dr. He, in an adaptive immune response there is a lag time between antigen exposure and response, which typically takes five to 10 days. This timing is faster with a memory response, so for a secondary vaccination it would take five to seven days.

Dr. Akbari provided no foundational support to show how a response involving both the innate and adaptive immune response can occur within 24 hours.

Case law illustrates that an adaptive immune response does not occur within one day.

See, e.g., Forrest v. Sec’y of Health & Hum. Servs., No. 14-1046V, 2019 WL 925495, at *6, *8 (Fed. Cl. Spec. Mstr. Jan. 28, 2019) (finding “a preponderance of the evidence shows that molecular mimicry is not likely to happen within 36 hours, even for a recall response,” as molecular mimicry is an adaptive immune response); Martinez ex rel. W.M. v. Sec’y of Health & Hum. Servs., No. 16-738V, 2022 WL 4884923, at *27 (Fed. Cl. Spec. Mstr. Sept. 9, 2022) (finding “a relative short onset” of one day “not medically acceptable” in an “an autoimmune reaction involving antibodies or other immune cells associated with the adaptive[] [] immune response in reaction to antigenic exposure” (emphasis omitted)), mot. for rev. denied, 165 Fed. Cl. 76 (2023); Langert v. Sec’y of Health & Hum. Servs., No. 22-809V, 2025 WL 1892418, at *6, *8 (Fed. Cl. Spec. Mstr. June 13, 2025) (“Such a short, one-day onset timeframe is not consistent with Petitioner’s causation theory . . . [which] involves the adaptive immune system— the secondary immune arm, which does not immediately respond to a vaccine upon administration. Rather, this process takes more than a day to result in the production of antibodies capable of a cross-reactive, autoimmune attack.” (internal citations omitted)); see also Brancheau v. Sec’y of Health & Hum. Servs., No. 21-1209V, 2024 WL 1619606, at *23-24 (Fed. Cl. Spec. Mstr. Mar. 21, 2024) (detailing the timing involved in the latency period between antigen exposure and peak adaptive immune response); infra Part V.C (analyzing Althen prong three).

B. Althen Prong Two

Under Althen prong two, Petitioner must prove by a preponderance of the evidence that there is a “logical sequence of cause and effect showing that the vaccination was the reason for the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “Petitioner must show that the vaccine was the ‘but for’ cause of the harm . . . or in other words, that the vaccine was the ‘reason for the injury.’” Pafford, 451 F.3d at 1356 (internal citations omitted).

In evaluating whether this prong is satisfied, the opinions and views of the vaccinee’s treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d at 1326 (“[M]edical records and medical opinion testimony are favored in vaccine cases, as treating physicians are likely to be in the best position to determine whether a ‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury.’” (quoting Althen, 418 F.3d at 1280)). Medical records are generally viewed as trustworthy evidence, since they are created contemporaneously with the treatment of the vaccinee. Cucuras, 993 F.2d at 1528. Petitioner need not make a specific type of evidentiary showing, i.e., “epidemiologic studies, rechallenge, the presence of pathological markers or genetic predisposition, or general acceptance in the scientific or medical communities to establish a logical sequence of cause and

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effect.” Capizzano, 440 F.3d at 1325. Instead, Petitioner may satisfy her burden by presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.

The undersigned finds there is not preponderant evidence in the record to support a logical sequence of cause-and-effect showing the October 16, 2019 flu vaccine to be the cause of Petitioner’s ITP. See Althen, 418 F.3d at 1278.

First, the records show a clinical course that is not consistent with the mechanism presented due to Petitioner’s onset of one day. Petitioner received a flu vaccination on October 16, 2019 in the afternoon. Within the next few hours, she began to experience uneasiness, shortness of breath, chills, shakiness, and body cramps. The following morning, on October 17, Petitioner woke up with petechiae/blood blisters on her face, chest, and legs, and inside her mouth. That afternoon, she presented to her allergist, who ordered blood work that revealed a platelet level of five. The undersigned finds an onset of one day inconsistent with the pathogenesis of ITP and the mechanism purported for the reasons described below in the Althen prong three analysis.

Second, although Petitioner’s treating hematologist documented an association between the flu vaccine and her ITP, the undersigned does not find this to be persuasive evidence of causation. On October 23, 2019, Dr. Dammrich, Petitioner’s hematologist, diagnosed Petitioner with ITP that was “possibly a reaction to flu shot as it happened immediately after.” Resp. Ex. 4 at 63. He further opined that Petitioner’s ITP was “[l]ikely precipitated by vaccination given the timing of onset.” Id. His diagnosis and opinions were unchanged throughout Petitioner’s visits.

Generally, treating physician statements are typically “favored” as treating physicians “are likely to be in the best position to determine whether a ‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury.’” Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1280). However, no treating physician’s views bind the special master, per se; rather, their views are carefully considered and evaluated. § 13(b)(1); Snyder, 88 Fed. Cl. at 746 n.67. “As with expert testimony offered to establish a theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the reasonableness of their suppositions or bases.” Welch v. Sec’y of Health & Hum. Servs., No. 18-494V, 2019 WL 3494360, at *8 (Fed. Cl. Spec. Mstr. July 2, 2019).

On balance, Dr. Dammrich’s statements appear to be based on the proximity and temporal association between vaccination and ITP. A “treating physician’s recognition of a temporal relationship does not advance the analysis of causation.” Isaac v. Sec’y of Health & Hum. Servs., No. 08-601V, 2012 WL 3609993, at *26 (Fed. Cl. Spec. Mstr. July 30, 2012), aff’d, 108 Fed. Cl. 743 (2013), aff’d, 540 Fed. App’x 999 (Fed. Cir. 2013). And a temporal relationship between a vaccine and an injury, standing alone, does not constitute preponderant evidence of vaccine causation. See, e.g., Veryzer v. Sec’y of Health & Hum. Servs., 100 Fed. Cl. 344, 356 (2011) (explaining that “a temporal relationship alone will not demonstrate the requisite causal link and that [P]etitioner must posit a medical theory causally connecting the vaccine and injury”), aff’d, 475 Fed. App’x 765 (Fed. Cir. 2012).

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Although Dr. Dammrich opined that Petitioner’s ITP was “[l]ikely precipitated by vaccination,” he did not explain the reasoning for his opinion. Dr. Dammrich is not an immunologist, and he did not discuss how a vaccination could invoke an adaptive immune response that could cause platelet destruction resulting in a very low platelet count of five within 24 hours. In contrast, Dr. He explains why it is not probable that this process could occur within one day, which is discussed more fully below.

Lastly, the parties appear to agree there was no identifiable alternative cause. However, this fact alone is not preponderant evidence “showing that the vaccination was the reason for the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). Thus, despite no alternative cause being identified, Petitioner fails to reach the level of preponderance required to satisfy the second Althen prong. de Bazan, 539 F.3d at 1351-52.

Accordingly, the undersigned finds that Petitioner has not satisfied her burden under Althen prong two.

C. Althen Prong Three

Althen prong three requires Petitioner to establish a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been defined as a “medically acceptable temporal relationship.” Id. The Petitioner must offer “preponderant proof that the onset of symptoms occurred within a time frame for which, given the medical understanding of the disorder’s etiology, it is medically acceptable to infer causation-in-fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically acceptable time frame must also be consistent with the theory of how the relevant vaccine can cause the injury alleged (under Althen Prong One). Id.; Koehn v. Sec’y of Health & Hum. Servs., 773 F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro, 101 Fed. Cl. at 542; see Pafford, 451 F.3d at 1358.

Petitioner received her flu vaccination on October 16, 2019. The parties and experts agree that Petitioner’s onset of neurological symptoms began within 24 hours or one day, by October 17, 2019. Even though Petitioner’s declaration averred her symptoms began “[w]ithin forty-eight (48) hours of [flu] vaccination,” her statements to her medical providers documented in the medical records and during the entitlement hearing indicate her symptoms began within one day of her flu vaccination. Pet. Ex. 7 at ¶ 3. Therefore, the undersigned finds onset to by October 17, 2019, within one day of her flu vaccination.

The next question is whether an onset of one day is an appropriate temporal interval given the proffered causal mechanism that includes the adaptive immune system. The undersigned finds it is not.

First, Petitioner provided no literature to support a finding that the adaptive immune system would result in platelet destruction and a low platelet count within one day. Dr. Akbari provided evidence that after a vaccination, inflammasomes and other cytokines involved in the innate immune system can be activated within one day. However, no evidence was provided to

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show inflammasomes, cytokines, or other innate immune systems cells can destroy platelets within one day. Without this foundational evidence, Dr. Akbari’s theory fails.

Dr. Akbari appears to assert that because inflammasomes and other cytokines are found in patients with ITP, inflammasomes and cytokines destroyed platelets causing ITP. However, this is a mischaracterization of the literature. Dr. Akbari failed to provide foundational evidence to bridge the gap between presence of inflammasomes and cytokines and the pathology of ITP. “An expert may ‘extrapolate from existing data,’ and use ‘circumstantial evidence,’ [b]ut the reasons for the extrapolation should be . . . persuasive.” K.O. v. Sec’y of Health & Hum. Servs., No. 13-472V, 2016 WL 7634491, at *12 (Fed. Cl. Spec. Mstr. July 7, 2016) (internal citations omitted) (first quoting Snyder v. Sec’y of Health & Hum. Servs., 88 Fed. Cl. 706, 743 (2009); and then quoting Althen, 418 F.3d at 1280). This is not a new issue to Dr. Akbari. See, e.g., Nieves v. Sec’y of Health & Hum. Servs., No. 18-1602V, 2023 WL 2580148, at *44-45 (Fed. Cl. Spec. Mstr. Apr. 17, 2023) (“[E]vidence that vaccines might stimulate production of some immune cells, or even interact with them, does not mean that the vaccine causes the injury . . . .”).

Relative to the adaptive immune system, as Dr. He and the IOM explain, there is latency between antigen exposure (i.e., flu vaccination) and the adaptive immune response. Resp. Ex. D7 at 86-87. In a primary (first) exposure, latency between antigen exposure and development of a response “is characterized by a lag phase, logarithmic phase, and plateau phase.” Id. at 87. The lag phase is thought to be four to seven days and development of the primary antibody response is seven to 10 days after exposure. Id. This latency period is shorter with subsequent exposures due to the development of memory cells; the lag phase is generally one to three days and the logarithmic phase occurs over the next 3 to 5 days. Id.

Even if Petitioner had a memory response due to receiving similar vaccines in the past (which Petitioner’s experts did not posit), it would not explain an onset of one day as it is too short. In order to conclude that there was a shortened latency period due to a memory response, foundational evidence is needed to establish that Petitioner received prior flu vaccinations that contained the same antigens as those she received in her 2019 flu vaccination. Although Petitioner stated she received prior flu vaccinations, there is no evidence to show what prior years she received prior flu vaccines, no evidence of the flu strains in prior flu vaccines she received or in the 2019 flu vaccination at issue, and no evidence of what antigens were in any of the prior vaccinations as compared to the 2019 vaccination. Thus, there is no evidence that Petitioner had repeated exposures to the same antigens that were in the 2019 vaccination that she received.

Overall, the undersigned finds Petitioner failed to provide foundational evidence in support of her theory of how ITP can occur within one day.

Further, Dr. Akbari at times mischaracterizes the literature, which adversely affects his credibility and the reliability of his opinions. This critique of Dr. Akbari is not new. See, e.g., Ray v. Sec’y of Health & Hum. Servs., No. 20-321V, 2025 WL 3900631, at *22-27 (Fed. Cl. Spec. Mstr. Dec. 12, 2025); Powell v. Sec’y of Health & Hum. Servs., No. 20-1726V, 2025 WL 3443590, at *32 (Fed. Cl. Spec. Mstr. Oct. 8, 2025); Williams v. Sec’y of Health & Hum. Servs.,

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No. 19-1269V, 2024 WL 5040482, at *43 (Fed. Cl. Spec. Mstr. Nov. 13, 2024); Nieves, 2023 WL 2580148, at *44-45 (noting Dr. Akbari “attempted to spin medical evidence” and had “several erroneous foundational contentions”).

Second, medical literature and case reports do not support an onset of 24 hours. Dr.

Ghose asserted the literature shows ITP can develop between one and 35 days after vaccination, however, his literature shows that onset of ITP occurred between four days and five weeks post- flu vaccination. See Pet. Ex. 18 at 1 (14 days); Pet. Ex. 20 at 1 (four days); Pet. Ex. 21 at 1-2 (four to five weeks); Pet. Ex. 23 at 2, 2 tbl. 1 (10 and 14 days); Pet. Ex. 32 at 1 (four days); Pet. Ex. 38 at 1 (26 days); Pet. Ex. 76 at 2 (one week). Dr. Ghose did not provide any literature to support an onset of ITP on the same day as flu vaccination, or within one day of flu vaccination.

Dr. Akbari also did not provide literature to support a one-day onset of ITP post-flu vaccination. Dr. Akbari cited a case report of one day onset from Yamamoto et al.; however, the authors noted “[t]he onset of vaccine-related ITP has a strict time relationship, developing within 4-35 days after [flu] vaccination.” Pet. Ex. 145 at 4. They further noted that although the patients had received previous vaccinations, “vaccine-related ITP may also have been incompatible given the too-short latency time.” Id. The authors concluded that the role of the flu vaccination “remains unclear, and further investigations are required.” Id.

Lastly, the undersigned finds that Vaccine Program case law does not support Petitioner’s case.

Vaccine Program ITP cases cited by Petitioner illustrate that onset of one day is not appropriate. Compensation has been granted where onset occurs at an appropriate time interval consistent with an adaptive immune response. Pet. Pre-Hearing Br. at 9; Pet. Post-Hearing Br. at 11-12. 95 In Mitchell, the undersigned found an onset of ITP 35 days after flu vaccination was appropriate given the adaptive immune mechanism of molecular mimicry. Mitchell v. Sec’y of Health & Hum. Servs., No. 19-1534V, 2023 WL 4483134, *27 (Fed. Cl. Spec. Mstr. Jan. 11, 2023). Similarly, the undersigned found the petitioner in Ferguson developed ITP symptoms within 30 days of tetanus-diphtheria-acellular pertussis (“Tdap”) vaccination and this timing was found to be appropriate given the mechanism of molecular mimicry. Ferguson ex rel. J.F. v. Sec’y of Health & Hum. Servs., No. 17-1737V, 2021 WL 6276204, *20-22 (Fed. Cl. Spec. Mstr. Dec. 10, 2021). These cases do not provide reasoning to support one-day onset. Thus, the undersigned finds Petitioner’s reliance on these cases misplaced.

In another Vaccine Program ITP case, compensation was denied where there was a rapid onset of ITP symptoms post-vaccination. In Brown, the special master found the petitioner’s ITP onset of two days post-vaccination was not consistent with the theory of molecular mimicry, an adaptive immune response. Brown v. Sec’y of Health & Hum. Servs., No. 20-426V, 2025 WL 4056839, *9-11 (Fed. Cl. Spec. Mstr. Dec. 16, 2025). The special master accepted the petitioner’s theory of molecular mimicry, but found none of the literature or case law supported such a rapid onset. Id.

95 The undersigned does not discuss or rely on Petitioner’s references to ITP cases that were informally resolved without a determination of entitlement. Pet. Post-Hearing Br. at 12, 12 n.2.

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While the above cases are not binding here, the undersigned agrees with the reasoning of other special masters as it relates to onset and Althen prong three. See Boatmon, 941 F.3d at 1358; Hanlon v. Sec’y of Health & Hum. Servs., 40 Fed. Cl. 625, 630 (1998), aff’d, 191 F.3d 1344 (Fed. Cir. 1999).

In summary, the undersigned finds by preponderant evidence that the onset of Petitioner’s ITP was October 17, 2019, within one day of her flu vaccination. Further, there is a lack of preponderant evidence to show that an onset of one day is appropriate given that ITP is caused by an adaptive immune system response that causes destruction of platelets.

Therefore, the undersigned finds the temporal association is not appropriate given the mechanism of injury. Petitioner has failed to satisfy the third Althen prong.

VI. CONCLUSION

The undersigned extends her sympathy to Petitioner for what she suffered due to her ITP.

The undersigned’s Decision, however, cannot be decided based upon sympathy, but rather on the evidence and law.

For the reasons discussed above, the undersigned finds that Petitioner has failed to establish by preponderant evidence that the flu vaccination she received caused her to develop ITP. Therefore, Petitioner is not entitled to compensation.

In the absence of a timely filed motion for review pursuant to Vaccine Rule 23, the Clerk of Court SHALL ENTER JUDGMENT in accordance with this Decision.

IT IS SO ORDERED.

s/Nora Beth Dorsey Nora Beth Dorsey Special Master