Allard v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 14-442V

Filed: March 9, 2020

* * * * * * * * * * * * * * *

ANGELA ALLARD, * TO BE PUBLISHED

*

Petitioner, *

v. * Dismissal; Ruling on the Record;

* Human Papillomavirus (“HPV”)

SECRETARY OF HEALTH * Vaccine; Idiopathic Thrombocytopenic

AND HUMAN SERVICES, * Purpura (“ITP”)

*

Respondent. *

* * * * * * * * * * * * * * *

Mark Sadaka, Esq., Mark T. Sadaka, LLC, Englewood, NJ, for petitioner.

Debra Begley, Esq., U.S. Department of Justice, Washington, DC, for respondent.

DECISION1

Roth, Special Master:

On May 23, 2014, Angela Allard (“Ms. Allard” or “petitioner”) filed a petition for

compensation pursuant to the National Vaccine Injury Compensation Program.2 Petitioner alleges

that she received a human papillomavirus (“HPV”) vaccination on June 2, 2011, and thereafter

suffered from idiopathic thrombocytopenic purpura (“ITP”), which was either caused or

significantly aggravated by the HPV vaccine. See Petition (“Pet.”), ECF No. 1. On November 15,

2018, petitioner filed a Motion for Ruling on the Record. ECF No. 88. After careful review of the

record, I find that petitioner has failed to carry her burden of showing that the HPV vaccination

caused or significantly aggravated her ITP. The petition is accordingly dismissed.

1

This Decision has been designated “to be published,” which means I am directing it to be posted on the Court of

Federal Claims’s website, in accordance with the E-Government Act of 2002, Pub. L. No. 107-347, 116 Stat. 2899,

2913 (codified as amended at 44 U.S.C. § 3501 note (2006)). This means the Decision will available to anyone with

access to the internet. However, the parties may object to the Decision’s inclusion of certain kinds of confidential

information. Specifically, under Vaccine Rule 18(b), each party has fourteen days within which to request redaction

“of any information furnished by that party: (1) that is a trade secret or commercial or financial in substance and is

privileged or confidential; or (2) that includes medical files or similar files, the disclosure of which would constitute

a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the whole Ruling will be available to the

public. Id.

2

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease of citation,

all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2012).

I. Procedural History

The petition was filed May 23, 2014. Petition, ECF No. 1. Petitioner filed medical records

on May 30, 2014 and July 2, 2014. Petitioner’s Exhibits (“Pet. Ex.”) 1-8, ECF Nos. 5, 7. On August

19, 2014, respondent filed his Rule 4(c) Report, stating that this matter was not appropriate for

compensation. Resp. Report, ECF No. 8. Petitioner continued to file additional medical records

through August of 2015. Pet. Ex. 9-19, ECF Nos. 9, 11, 22-23, 27, 30-31.

On December 4, 2015, petitioner filed an expert report from Dr. Eric Gershwin. Pet. Ex.

20-21, ECF No. 34. Petitioner later filed supporting medical literature. Pet. Ex. 22-101, ECF No.

36. A status conference was held on January 7, 2016. The special master previously assigned to

this matter discussed Dr. Gershwin’s expert report with the parties and identified several issues for

Dr. Gershwin to address in a supplemental expert report. Scheduling Order at 1-2, ECF No. 35.3

Petitioner filed a supplemental expert report from Dr. Gershwin on February 25, 2016. Pet.

Ex. 103, ECF No. 40. Petitioner filed additional medical records on March 17, 2016. Pet. Ex.

104.1-104.3, ECF No. 41.

Respondent filed expert reports from Dr. Thomas Forsthuber and Dr. Steven McKenzie on

June 27, 2016. Resp. Ex. A-B, ECF No. 45.

A status conference was held on August 3, 2016. Petitioner was ordered to file a

supplemental report from Dr. Gershwin specifically addressing issues associated with petitioner’s

medical history, including petitioner’s Gardnerella infection, petitioner’s use of phentermine at the

time of her vaccination, petitioner’s prior instances of ITP, and an assault that petitioner endured

that led to an emergency room visit on June 5, 2011. Scheduling Order at 1, ECF No. 47.

Additionally, respondent stated that his expert hematologist had noted references to platelet counts

dating from December of 2009 that had not been filed into the record. Id. Petitioner was ordered

to file a status report regarding attempts to locate her platelet counts between December of 2009

and June 2, 2011, the date of vaccination. Id. at 1-2.

Petitioner filed medical records in October and December of 2016. Pet. Ex. 130-131, ECF

Nos. 52, 54-55. These records did not include information regarding petitioner’s platelet counts in

2009 through the date of vaccination, June 2, 2011. Petitioner filed a third report from Dr.

Gershwin on December 19, 2016. Pet. Ex. 132, ECF No. 56.

During a status conference held on February 7, 2017, I noted that Dr. Gershwin’s third

report did not address any of the issues that he was asked to address during the previous status

conference. Scheduling Order at 1, ECF No. 57. Petitioner was ordered to file an additional report

from Dr. Gershwin addressing those issues. Id. Medical records documenting petitioner’s platelet

counts from December 2009 through 2011 had not been filed; petitioner advised that he had filed

all records received but they did not include any platelet counts between December 2009 and June

of 2011. Id. Respondent noted that Petitioner’s Exhibit 102 contained records from “Catholic

Healthcare West” and suggested that there may be additional records from that facility that had

3

This case was reassigned to me on January 13, 2016. ECF No. 37.

2

not yet been filed. Id. Petitioner was given 90 days to secure and file the missing medical records.

Id. at 1-2. Petitioner’s counsel was directed to consult with his client to determine if the relevant

records were available through another facility. Id. at 2.

Petitioner filed additional medical records on April 28, 2017. Pet. Ex. 133, ECF No. 61.

These records did not include information regarding petitioner’s platelet counts from 2009 through

June 2, 2011. See id.

Petitioner filed a status report on May 8, 2017, advising that, despite requests to various

healthcare providers, she had been unable to locate lab results documenting petitioner’s platelet

counts between 2009 and 2011. Pet. S.R. at 1, ECF No. 62. Petitioner filed a fourth report from

Dr. Gershwin and medical literature on June 12, 2017. Pet. Ex. 134-39, ECF No. 64.

A status conference was held on August 22, 2017, during which I emphasized that

petitioner’s bloodwork from 2009 to 2011 was important to the ultimate outcome of this matter.

Scheduling Order at 1, ECF No. 65. I encouraged petitioner’s counsel to continue his efforts to

locate these lab results. Id. Petitioner filed additional medical records in September and October

of 2017. Pet. Ex. 140-41, ECF No. 66-67. These records showed that petitioner had an abnormally

low platelet count on October 20, 2009, when she was not pregnant. Pet. Ex. 140 at 67. These

medical records contained no reference to petitioner’s platelet counts in 2010 or 2011.

Respondent filed supplemental expert reports from Dr. McKenzie and Dr. Forsthuber on

April 18, 2018. Resp. Ex. C-D, ECF No. 77.

A status conference was held on May 15, 2018. I noted respondent’s experts’ opinions that

petitioner’s low platelet count in October 2009 indicated that she had ITP unrelated to pregnancy.

Scheduling Order at 1, ECF No. 79. I further noted that Dr. Gershwin opined that the HPV vaccine

caused petitioner’s ITP but had not provided a mechanism by which the HPV vaccine could trigger

ITP. Id. at 2. I advised petitioner that Dr. Gershwin needed to provide a plausible biological

mechanism causally connecting the HPV vaccine to the development or aggravation of ITP and

address the issues raised by respondent’s experts, including the fact that petitioner had low platelet

counts in October of 2009 when she was not pregnant, which suggested that she had ITP prior to

her HPV vaccination. Id. Petitioner was ordered to file either a supplemental expert report or a

status report by July 16, 2018. Id.

On June 11, 2018, petitioner filed a status report stating that she had received consistent

medical treatment from January 2009 through September 2010, and although petitioner’s records

document a low platelet count in October 2009, she was found to have normal platelet counts on

follow-up labs performed on December 22, 2009. Pet. S.R. at 1-2, ECF No. 80. However, no lab

records to substantiate this representation from December 2009 through June 2011 were ever filed.

An entitlement hearing was scheduled to begin on November 13, 2019. See Prehearing

Order, ECF No. 83. On September 14, 2019, petitioner filed a status report indicating that she

intended to file a Motion for a Ruling on the Record instead of proceeding to an entitlement

hearing. See Pet. S.R., ECF No. 84. Accordingly, the entitlement hearing was cancelled. ECF No.

85.

3

Petitioner filed a Motion for a Ruling on the Record on November 15, 2018. ECF No. 88.

Respondent filed updated medical literature and a response to petitioner’s motion on April 23,

2019. Resp. Ex. C1-3, ECF No. 92; Response, ECF No. 93. Petitioner filed a reply on April 30,

2019. Reply, ECF No. 94.

This matter is now ripe for decision.

II. Overview of ITP

Idiopathic thrombocytopenic purpura is a common autoimmune disorder of unknown

etiology characterized by immune-mediated platelet destruction and impaired platelet formation.

Resp. Ex. A at 3 (citing Resp. Ex. A24 at 306; Resp. Ex. A35 at 344; Resp. Ex. A46 at 6512-13).

The British Society of Hematology defines ITP as “an autoimmune disorder characterized by

persistent thrombocytopenia due to autoantibody binding to platelet antigen(s) causing their

premature destruction by the reticuloendothelial system,7 and in particular the spleen.” Pet. Ex. 20

at 3 (citing Pet. Ex. 378 at 4). ITP has been described as a syndrome as there is no one single cause.

Resp. Ex. B at 4 (citing Resp. Ex. B39 at 396). It typically presents as either primary ITP, unrelated

to other diseases or external factors, or secondary ITP associated with other conditions including

autoimmune diseases and infections such as measles, mumps, rubella, varicella, H. pylori, and

hepatitis C, drugs, or other risk factors including pregnancy.10 Resp. Ex. A at 3 (citing Resp. Ex.

A4 at 6513-15); Resp. Ex B at 4 (citing Resp. Ex. B3 at 396).

The average person generally has platelet levels of 150 k/ul (thousand per microliter) or

higher. Resp. Ex. B at 1-2. When a person’s platelet count drops below that, a diagnosis of

thrombocytopenia is appropriate. Id. A platelet count between 50 and 150 k/ul is indicative of mild

4

Jill Johnson, Pathogenesis in Immune Thrombocytopenia: New Insights, AM. SOC’Y OF HEMATOLOGY 306-12

(2012), filed as Resp. Ex. A2.

5

Sean Deane et al., The Geoepidemiology of Immune Thrombocytopenic Purpura, 9 AUTOIMMUNITY REVS. 342

(2010), filed as Resp. Ex. A3.

6

Douglas B. Cines et al., The ITP Syndrome: Pathogenic and Clinical Diversity, 113 BLOOD 6511 (2009), filed as

Resp. Ex. A4.

7

The reticuloendothelial system is “a group of cells having the ability to take up and sequester inert particles and vital

dyes; it includes macrophages and macrophage precursors; specialized endothelial cells lining the sinusoids of the

liver, spleen, and bone marrow.” Reticuloendothelial system, DORLAND’S at 1862.

8

James N. George et al., Idiopathic Thrombocytopenic Purpura: A Practice Guideline Developed by Explicit Methods

for The American Society of Hematology, 88 BLOOD 3 (1996), filed as Pet. Ex. 37.

9

Adam Cuker et al., Can Immune Thrombocytopenia Be Cured with Medical Therapy, 41 SEMINARS IN THROMBOSIS

& HEMOSTASIS 395 (2015), filed as Resp. Ex. B3.

10

Pregnancy-induced ITP typically presents in the first trimester and platelet counts in patients with pregnancy-

induced ITP can drop lower than 70 k/ul, both of which are atypical in patients with gestational thrombocytopenia.

See Pet. Ex. 2 at 125-29; Resp. Ex. A at 3 (citing Resp. Ex. A5 at 397-98). Keith R. McCrae, Thrombocytopenia in

Pregnancy, AM. SOC’Y OF HEMATOLOGY 397 (2010), filed as Resp. Ex. A5.

4

thrombocytopenia, a count between 20 and 50 k/ul is considered moderate, and severe

thrombocytopenia occurs when a blood count drops below 20 k/ul. Id. at 2.

Gestational thrombocytopenia (“GT”) is relatively common during pregnancy and is

characterized by “incidental and clinically asymptomatic thrombocytopenia in the absence of

previous thrombocytopenia, which resolves spontaneously after delivery.” Resp. Ex. A at 3 (citing

Resp. Ex. A5 at 397-98). “Platelet counts in GT rarely fall below [70 k/ul] and gestational

thrombocytopenia usually becomes apparent during the second and third trimester,” as opposed to

pregnancy-induced ITP which presents in the first trimester with platelet counts that drop below

70 k/ul. Id. (citing Resp. Ex. A611 at 47-48); see Pet. Ex. 2 at 125-29. However, it can be difficult

to clinically distinguish between gestational thrombocytopenia and ITP and is usually

accomplished with ongoing follow-up after delivery. Id. (citing Resp. Ex. A6 at 48).

III. Petitioner’s Medical History

A. Petitioner’s Medical History Prior to the Allegedly Causal Vaccination

Petitioner initially suffered from an abnormally low platelet count when she was pregnant

with her first child in 2007. Pet. Ex. 9 at 1. Between July and August 2007, petitioner’s platelet

count fluctuated between 41 k/ul and 55 k/ul. See id. at 67, 73. Shortly before giving birth,

petitioner was given oral steroids on September 14, 2007, which caused her platelet count to rise

to 82 k/ul. Id. at 75. After giving birth on September 19, 2007, petitioner’s platelet count was 102

k/ul and rose to 168 k/ul by September 21, 2007. Id. at 67.

No records were filed thereafter until 2009 when petitioner was pregnant with her second

child. Her platelet counts were monitored throughout her pregnancy and she had normal platelets

counts in January of 2009 and again in March of 2009, when she delivered her second child. Pet.

Ex. 141 at 30, 120. No records were filed thereafter until October 20, 2009, when petitioner had a

platelet count of 100 k/ul, which is below the average platelet count of 150 k/ul. Pet. Ex. 140 at

67. Petitioner was not pregnant on this date. See id.

Despite multiple requests from the court and respondent’s counsel,12 petitioner failed to

file any lab work from 2010 or 2011 prior to her receipt of the allegedly causal vaccine, so it is

unknown if her platelet count continued to be low after October 20, 2009. See Resp. Response at

2, ECF No. 93.

11

Junko Kasai et al., Clinical Features of Gestational Thrombocytopenia Difficult to Differentiate from Immune

Thrombocytopenia Diagnosed During Pregnancy, 41 J. OBSTETRICS & GYNECOLOGY RESEARCH 44 (Jan. 2015), filed

as Resp. Ex. A6.

12

During status conferences held on August 3, 2016, February 7, 2017, and August 22, 2017, I specifically requested

that petitioner file any records containing petitioner’s platelet counts during 2010 and 2011 as they are necessary for

her to prove her claim. See Scheduling Orders, ECF Nos. 47, 57, 65.

5

B. Petitioner’s Medical History at the Time of and Following the Allegedly Causal

Vaccination

On May 24, 2011, petitioner presented to Sutter Amador Women’s Services for an annual

women’s health exam. Pet. Ex. 1 at 17. At this visit she tested positive for Gardnerella 13 and a

physical exam revealed “HPV genital warts.” Id. at 17, 64. She also reported abnormal bleeding

while she had been on Mirena.14 Id. at 64. She was prescribed Aldera cream15 to be used three

times per week. Id. at 64. She was noted to be due for Gardasil and Tdap immunizations. Pet. Ex.

1 at 63-64. She also reported being under significant stress due to a change in jobs and her two

special needs children. Id. There is some discrepancy as to when petitioner received the allegedly

causal HPV vaccine. One record indicates she received the HPV vaccine at her visit on May 24,

2011 and another record suggests she received the HPV vaccine on June 2, 2011. See Pet. Ex. 1 at

49, 56; but see Pet. Ex. 1 at 46.

On June 5, 2011, petitioner presented to Lodi Memorial Hospital where she reported that

she had been assaulted by her ex-boyfriend the previous night. Pet. Ex. 16 at 9-10. She stated that

she felt “sore all over” with neck, back, and elbow pain, headache, and abrasions. Id. She had been

taking 1 tab of phentermine16 daily. Id. at 8. She left the hospital against medical advice. Id. at 19.

On June 14, 2011, petitioner presented to Women’s Health Services for an ultrasound

following a positive at-home pregnancy test. Pet. Ex. 1 at 62, 81. The ultrasound confirmed that

she was approximately four weeks pregnant. Id. at 62.

On July 5, 2011, petitioner’s lab work revealed a platelet count of 64 k/ul. Pet. Ex. 1 at 12.

On July 8, 2011 petitioner presented to Sutter Amador emergency department for vaginal

bleeding which started one day earlier and unusual bruising that had started one week prior. Pet.

Ex. 3 at 2, 6. Petitioner reported that she had experienced similar symptoms and low platelet counts

during a previous pregnancy. Id. Her platelet count at this visit was 66 k/ul. Id. at 4.

13

Gardnerella is defined as “a genus of small, pleomorphic, gram-negative rod-shaped bacteria found in the normal

female genital tract and also as a major case of bacterial vaginitis.” Gardnerella, DORLAND’S ILLUSTRATED MEDICAL

DICTIONARY 761 (32d ed. 2012) [hereinafter DORLAND’S]. Vaginitis is defined as “inflammation of the vagina; it is

marked by pain and by a purulent discharge.” Vaginitis, DORLAND’S at 2019.

14

Mirena is defined as “trademark for a preparation of levonorgestrel.” Mirena, DORLAND’S at 1168. Levonorgestrel

is defined as “the levorotatory form of norgestrel, administered as a subdermal contraceptive implant or in combination

with an estrogen component in an oral contraceptive.” Levonorgestrel, DORLAND’S at 1032.

15

The active ingredient of Aldera cream is Imiquimod, which is defined as “a biologic response modifier used topically

in the treatment of condyloma acuminatum of the external genitalia and perianal region.” Resp. Ex. D at 2; Imiquimod,

DORLAND’S at 916. Condyloma acuminatum is defined as “a type of papilloma usually found on the mucous membrane

or skin of the external genitals or in the perianal region. Lesions are usually few in number but may aggregate to form

large cauliflowerlike masses.” Condyloma acuminatum, DORLAND’S at 402.

16

Phentermine is a weight-loss medication associated with many side effects including gastrointestinal issues,

constipation and diarrhea. Resp. Ex. D at 2.

6

On July 11, 2011, petitioner tested positive for platelet specific antibodies. Pet. Ex. 1 at 10.

She also had a low platelet count at 73 k/ul and a low lymphocyte count. Id. at 11.

On August 4, 2011, petitioner’s platelet count dropped to 20 k/ul but increased to 133 k/ul

after taking 100 mg of prednisone.17 Pet. Ex. 1 at 51, 61.

On August 10, 2011, petitioner presented to Dr. Kiwan, a hematologist, for treatment of

her low platelet counts. Pet. Ex. 2 at 125. Petitioner reported her current symptoms included easy

bruising, gingival bleeding, and vaginal spotting. Id. Petitioner’s platelet count at this visit was 20

k/ul. Id. Dr. Kiwan noted that petitioner was twelve weeks pregnant and indicated that because

petitioner had such low platelet levels during her first trimester, she qualified for a diagnosis of

ITP rather than a diagnosis of gestational thrombocytopenia. Pet. Ex. 2 at 125-28. Dr. Kiwan

explained that platelet counts in patients with gestational thrombocytopenia typically do not fall

below 70 k/ul, and when platelet levels drop lower, an ITP diagnosis is more appropriate. Id. at

126.

Petitioner’s platelet count was monitored regularly during the final months of her

pregnancy. Her platelet counts fluctuated between 12 k/ul and 184 k/ul and she experienced several

bouts of major vaginal bleeding. See Pet. Ex. 1 at 8; Pet. Ex. 2 at 45, 76-79, 83-90, 128, 133, 139;

Pet. Ex. 141 at 171. She was treated with oral steroids and intravenous immune globulin (“IVIG”)

treatments. See Pet. Ex. 2 at 76-77, 131-33, 139.

On December 19, 2011, petitioner presented to the Sutter Health emergency department

for premature rupture of the membranes and uterine contractions. Pet. Ex. 5 at 118-20. She was

treated with antibiotics to prevent infection and attempt to prolong her pregnancy. Id. at 120.

Petitioner delivered her third child via Caesarean section on December 22, 2011. Id. at

281-84.

On December 23, 2011, petitioner’s platelet count had improved to 105 k/ul. Pet. Ex. 5 at

302. By December 28, 2011, her platelets were at 270 k/ul. Pet. Ex. 2 at 94. Her baby was

diagnosed with transient thrombocytopenia and treated with IVIG immediately after delivery. Id.

Petitioner discontinued oral steroids on her own on February 1, 2012. Id. at 94. By February

6, 2012, her platelet count was down to 9 k/ul. Id. She was noted to have recurrent ITP and was

restarted on 80 mg of prednisone daily and a course of IVIG. Id.

Petitioner presented to Dr. Kiwan on February 14, 2012. Id. at 96. Petitioner’s platelet

count was up to 322 k/ul and accordingly, she was started on a gradual steroid taper. Id.

17

Prednisone is defined as “a synthetic glucocorticoid derived from cortisone, administered orally as an anti-

inflammatory and immunosuppressant in a wide variety of disorders.” Prednisone, DORLAND’S at 1509.

Glucocorticoid is defined as “any of the corticosteroids (steroids produced by the adrenal cortex) that regulate

carbohydrate, lipid, and protein metabolism and inhibit the release of corticotropin.” Glucocorticoid, DORLAND’S at

789.

7

Petitioner returned to Dr. Kiwan on March 13, 2012 requesting that she be taken off

prednisone and advising that she had begun tapering it faster than recommended. Id. at 100. Her

platelets were at 111 k/ul. Id. Due to continued side-effects from steroids and her request, she was

switched to rituximab. Id. at 100-01.

Petitioner returned to Dr. Kiwan on March 21, 2012 and April 20, 2012 with progressive

fatigue and platelet counts of 51 k/ul and 56 k/ul. Id. at 105-07, 110-12. She was continued on

rituximab. Id. at 105.

On June 6, 2012, petitioner presented to Dr. Kiwan with a platelet count of 52 k/ul and

reports of easy bruising and fatigue. Id. at 115. Dr. Kiwan noted that testing from June 4, 2012

revealed that petitioner’s platelet count had fallen to 25 k/ul while she was suffering from a urinary

tract infection. Id. at 119. Dr. Kiwan decided to hold any further treatment until and unless

petitioner’s platelets fell below 50 k/ul again. Id.

Petitioner presented to the Sutter Memorial Hospital emergency department on August 1,

2012 with complaints of a constant skin rash on her trunk and lower extremities that had persisted

for five weeks. Pet. Ex. 5 at 69. She was noted to have a history of ITP. Id. At this visit, petitioner’s

platelet count was 47 k/ul. Id. at 70.

On November 15, 2012, petitioner returned to Dr. Kiwan. She had recently been diagnosed

with pleurisy.18 Pet. Ex. 8 at 27. Her platelet count was 77 k/ul. Id. at 30. Dr. Kiwan noted that

petitioner was taking ibuprofen for her pleurisy and had developed mild hemoptysis. 19 Id. at 27-

29, 36.

On February 1, 2013, petitioner had a follow up visit with Dr. Kiwan, who noted that

petitioner received an HPV vaccine “two weeks” before her symptoms began, though he did not

explain where this information came from. Id. at 35. Her platelet count was 115 k/ul. Id.

On August 20, 2013, petitioner presented to Dr. D’Acquisto, an oncologist, complaining

of skin rashes, headaches, left facial numbness, lower abdominal pain, pleurisy, constant chest

discomfort, and severe fatigue. Pet. Ex. 7 at 3-5. Her platelet count was 89 k/ul. Id. at 6. Dr.

D’Acquisto agreed with the diagnosis of ITP. Id. He explained to petitioner that because she was

refusing to take oral steroids, and because her condition did not resolve with IVIG or rituximab,

the only other treatment available was a splenectomy, which was not imperative because she was

stable. Id.

18

Pleurisy is defined as “inflammation of the pleura, with exudation into its cavity and upon its surface . . . Symptoms

include localized chest pain and dry cough.” Pleurisy, DORLAND’S at 1461.

19

Hemoptysis is defined as “the expectoration of blood or of blood-stained sputum.” Hemoptysis, DORLAND’S at 842.

8

Petitioner returned to Dr. D’Acquisto on September 5, 2013. Id. at 10. Her platelet count

was 89 k/ul. Id. An abdominal CT ruled out splenomegaly20 and secondary hypersplenism.21 Id. at

11. He noted that petitioner’s “multiple somatic complaints are not explained by the ITP.” Id.

During a follow-up visit with Dr. D’Acquisto on December 15, 2013, petitioner had a

platelet count of 75 k/ul. Id. at 9. She was diagnosed with stable chronic ITP. Id.

On January 20, 2014, petitioner had a platelet count of 183 k/ul. Pet. Ex. 7 at 15. No further

medical records were filed.

IV. The Experts

A. Petitioner’s Expert, Dr. M. Eric Gershwin

Petitioner filed four expert reports from her expert, Dr. M. Eric Gershwin. See Pet. Ex. 20,

103, 132, 134. Dr. Gershwin obtained his medical degree from Stanford University and completed

his residency at Tufts-New England Medical Center. Pet. Ex. 21 at 1-2. He is board certified in

rheumatology, allergy, and clinical immunology. Id. at 2. He has been a Professor of Medicine in

Rheumatology, Allergy, and Clinical Immunology at the University of California School of

Medicine at Davis since 1981. Id.

B. Respondent’s Expert, Dr. Thomas Forsthuber

Respondent filed two expert reports from Dr. Thomas Forsthuber. See Resp. Ex. A, D. Dr.

Forsthuber received his medical degree from the University of Tubingen in Germany and

completed his residency at University Hospitals of Cleveland. Resp. Ex. A1 at 3. He is board

certified in anatomical and clinical pathology. He has been a Professor of Immunology at the

University of Texas at San Antonio since 2005. Id. He also holds adjunct appointments in

pathology, microbiology, and immunology at the University of Texas Health Sciences Center. Id.

at 3-4.

C. Respondent’s Expert, Dr. Steven McKenzie

Respondent filed two expert reports from Dr. Steven McKenzie. See Resp. Ex. B, C. Dr.

McKenzie has a medical degree and a doctoral degree in bioengineering from the University of

Pennsylvania. Resp. Ex. B, Tab 1, at 2. He completed both a residency in pediatrics and a

fellowship in pediatric hematology-oncology at Children’s Hospital of Philadelphia. Id. He is

board certified in pediatrics and pediatric hematology/oncology. He has been a Professor of

Medicine and Pediatrics at Thomas Jefferson University since 2000. Id. at 3.

20

Splenomegaly is defined as “enlargement of the spleen.” Splenomegaly, DORLAND’S at 1752.

21

Hypersplenism is defined as “a condition characterized by exaggeration of the suggested inhibitory or destructive

functions of the spleen, resulting in deficiency of the peripheral blood elements, singly or in combination,

hypercellularity of the bone marrow, and usually, but not always, splenomegaly.” Hypersplenism, DORLAND’S at 896.

9

V. Discussion

A. Legal Standard

The Vaccine Act provides two avenues for petitioners to receive compensation. First, a

petitioner may demonstrate a “Table” injury—i.e., an injury listed on the Vaccine Injury Table

that occurred within the provided time period. § 11(c)(1)(C)(i). “In such a case, causation is

presumed.” Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006);

see § 13(a)(1)(B). Second, where the alleged injury is not listed on the Vaccine Injury Table, a

petitioner may demonstrate an “off-Table” injury, which requires that the petitioner “prove by a

preponderance of the evidence that the vaccine at issue caused the injury.” Capizzano, 440 F.3d at

1320; see § 11(c)(1)(C)(ii).

To prove causation for an “off-Table” injury, petitioner must satisfy the three-pronged test

established in Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir. 2005). Althen

requires that petitioner show by preponderant evidence that the vaccination caused his injury “by

providing: (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.” Id. at 1278. A

petitioner need not show that the vaccination was the sole cause, or even the predominant cause,

of the alleged injury; showing that the vaccination was a “substantial factor” and a “but for” cause

of the injury is sufficient for recovery. Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352,

1355 (Fed. Cir. 2006); Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir.

1999).22 Causation is determined on a case-by-case basis, with “no hard and fast per se scientific

or medical rules.” Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994).

Petitioner is not required to identify “specific biological mechanisms” to establish causation, nor

are they required to present “epidemiologic studies, rechallenge, the presence of pathological

markers or genetic disposition, or general acceptance in the scientific or medical communities.”

Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). “[C]lose calls regarding causation

are resolved in favor of injured claimants.” Althen, 418 F.3d at 1280. Once a petitioner has proven

causation by preponderant evidence, “the burden then shifts to the respondent to show by a

preponderance of the evidence that the injury is due to factors unrelated to the administration of

the vaccine.” Deribeaux ex rel. Deribeaux v. Sec’y of Health & Human Servs., 717 F.3d 1363,

1367 (Fed. Cir. 2013) (citing § 13(a)(1)(B)).

The process for making factual determinations in Vaccine Program cases begins with

analyzing the medical records, which are required to be filed with the petition. § 11(c)(2). Medical

records created contemporaneously with the events they describe are presumed to be accurate and

“complete” such that they present all relevant information on a patient’s health problems. Cucuras

v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). In making

contemporaneous reports, “accuracy has an extra premium” given that the “proper treatment

hang[s] in the balance.” Id. Contemporaneous medical records that are clear, consistent, and

complete warrant substantial weight “as trustworthy evidence.” Id. Indeed, “where later testimony

22

The Vaccine Act also requires petitioners to show by preponderant evidence that the “residual effects or

complications” of the alleged vaccine-related injury lasted for more than six months. § 11(c)(1)(D)(i). It is undisputed

that this six-month requirement is satisfied in this case.

10

conflicts with earlier contemporaneous documents, courts generally give the contemporaneous

documentation more weight.” Campbell ex rel. Campbell v. Sec’y of Health & Human Servs., 69

Fed. Cl. 775, 779 (2006); see United States v. U.S. Gypsum Co., 333 U.S. 364, 396 (1948). But

petitioners can support their claim with oral testimony if it is credible and consistent with the

medical records. See, e.g., Stevenson ex rel. Stevenson v. Sec’y of Health & Human Servs., No. 90-

2127V, 1994 WL 808592, at *7 (Fed. Cl. Spec. Mstr. June 27, 1994) (crediting the testimony of a

fact witness whose “memory was sound” and “recollections were consistent with the other factual

evidence”). In short, “the record as a whole” must be considered. § 13(a).

Furthermore, establishing a sound and reliable medical theory connecting the vaccine to

the injury often requires a petitioner to present expert testimony in support of his or her claim.

Boatmon v. Sec’y of Health & Human Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019); Lampe v.

Sec’y of Health & Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). The Supreme Court’s

opinion in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), requires that

courts determine the reliability of an expert opinion before it may be considered as evidence. “In

short, the requirement that an expert’s testimony pertain to ‘scientific knowledge’ establishes a

standard of evidentiary reliability.” Id. at 590 (citation omitted). Thus, for Vaccine Act claims, a

“special master is entitled to require some indicia of reliability to support the assertion of the expert

witness.” Moberly ex rel. Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1324 (Fed.

Cir. 2010). The Daubert factors are used in the weighing of the reliability of scientific evidence

proffered. Davis v. Sec’y of Health & Human Servs., 94 Fed. Cl. 53, 66-67 (2010) (“uniquely in

this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging

tool with respect to persuasiveness of expert testimony already admitted”). Where both sides offer

expert testimony, a special master’s decision may be “based on the credibility of the experts and

the relative persuasiveness of their competing theories.” Broekelschen v. Sec’y of Health & Human

Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing Lampe, 219 F.3d at 1362). And nothing

requires the acceptance of an expert’s conclusion “connected to existing data only by the ipse dixit

of the expert,” especially if “there is simply too great an analytical gap between the data and the

opinion proffered.” Snyder ex rel. Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 743

(2009) (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)).

Finally, although this decision discusses some but not all of the literature in detail, I have

reviewed and considered all of the medical records and literature submitted in this matter. See

Moriarty ex rel. Moriarty v. Sec’y of Health & Human 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 & Human 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).

B. Analysis of Althen Factors

Because petitioner does not allege an injury listed on the Vaccine Injury Table, her claim

is classified as “off-Table.” As noted above, for petitioner to prevail on an “off-Table” claim, she

must show by preponderant evidence that her injury resulted from the vaccination at issue.

11

Capizzano, 440 F.3d at 1320. Doing so shifts the burden to respondent to show that the injury was

caused by factors unrelated to the vaccination. Deribeaux, 717 F.3d at 1367.

As an initial matter, the parties do not dispute that petitioner has ITP. Response at 8.

Therefore, in order to prevail, petitioner must establish by preponderant evidence a medical theory

that causally connects her ITP and receipt of the HPV vaccination.

1. Petitioner Failed to Advance a Sound and Reliable Medical Theory

The first Althen prong requires petitioner to provide a “reputable medical theory”

demonstrating that the vaccines received can cause the type of injury alleged. Pafford, 451 F.3d at

1355-56 (citation omitted). To satisfy this prong, petitioner’s “theory of causation must be

supported by a ‘reputable medical or scientific explanation.’” Andreu ex rel. Andreu v. Sec’y of

Health & Human Servs., 569 F.3d 1367, 1379 (Fed. Cir. 2009) (quoting Althen, 418 F.3d at 1278).

This theory need only be “legally probable, not medically or scientifically certain.” Id. at 1380

(emphasis omitted) (quoting Knudsen, 35 F.3d at 548). This standard was recently clarified by the

Federal Circuit. See Boatmon, 941 F.3d at 1359-60 (stating that the correct standard for Althen

prong one is “reputable,” and “sound and reliable” not a “lower reasonable standard” (internal

quotations omitted)). Nevertheless, “petitioners [must] proffer trustworthy testimony from experts

who can find support for their theories in medical literature.” LaLonde v. Sec’y of Health & Human

Servs., 746 F.3d 1334, 1341 (Fed. Cir. 2014). In this case, petitioner has not offered a reputable

medical theory of causation that the HPV vaccine caused or significantly aggravated petitioner’s

ITP.

Dr. Gershwin opined that an HPV vaccine can cause ITP via molecular mimicry, stating,

“Molecular mimicry is considered to be the primary molecular mechanism by which ITP develops

. . .”. Pet. Ex. 20 at 11. He quoted literature discussing molecular mimicry as a mechanism by

which autoimmune disorders can be caused, but never specifically discussed how the HPV

vaccination can cause ITP via this mechanism. See Pet. Ex. 103 at 1 (citing Pet. Ex. 10623 at 159).

Dr. Gershwin also attempted to compare the measles-mumps-rubella (“MMR”) to the HPV

vaccines, citing several articles discussing molecular mimicry as the mechanism by which the

MMR vaccine can cause ITP but neglected to explain the similarities between the two vaccinations

to warrant such a comparison. Pet. Ex. 20 at 10 (citing Pet. Ex. 8924 at 228-29; Pet. Ex. 9025 at 613;

23

Michael B.A. Oldstone, Molecular Mimicry: Its Evolution from Concept to Mechanism as a Cuase of Autoimmune

Diseases, 33 MONOCLONAL ANTIBODIES IN IMMUNODIAGNOSIS & IMMUNOTHERAPY 158 (2014), filed as Pet. Ex. 106.

24

E. Miller et al., Idiopathic Thrombocytopenic Purpura and MMR Vaccine, 84 ARCH DIS CHILD 227 (2015), filed as

Pet. Ex. 89.

25

Jan Neiderud, Thrombocytopenic Purpura After a Combined Vaccine Against Morbilli, Parotitis and Rubella, 72

ACTA PADIATR SCAND 613 (1983), filed as Pet. Ex. 90.

12

Pet. Ex. 9126 at 1265-67; Pet. Ex. 9227 at 268-70; Pet. Ex. 9328 at 354-56; Pet. Ex. 9429 at 1604-05;

Pet. Ex. 9530 at 568-69).

Dr. Gershwin submitted that ITP is commonly associated with community-acquired viral

infections, rubella infection, and the administration of live viral vaccinations. Id. at 8 (citing Pet.

Ex. 3831 at 582). Dr. Gershwin wrote, to that end, a causal relationship between the MMR

vaccination and ITP was accepted in the 1994 Institute of Medicine Report on the grounds of

biological plausibility. Id. at 9 (citing Pet. Ex. 94 at 1605). Dr. Gershwin further described the

pathophysiology of ITP in terms of the promiscuous response against platelet antigens and noted

that this was like other autoimmune diseases, which tend to reflect a genetic predisposition and

environmental factors. Id. (citing Pet. Ex. 4332 at 6516-19; Pet. Ex. 9633 at 156-57). However, Dr.

Gershwin did not clarify what environmental factors he was referring to. See id.

Dr. Gershwin conceded that while there have been attempts to study whether the HPV

vaccine is associated with the change in the risk of autoimmunity in young women, the authors of

these studies did not detect an increase in the prevalence of ITP in the study participants. Id.34 He

also cited a 2013 study from Denmark and Sweden in which almost one million girls who received

the HPV vaccine were studied to find evidence supporting an association between the vaccine and

autoimmunity, but no such evidence was found. Id. (citing Pet. Ex. 10135 at 4-5).

26

Margareta Bottiger, Swedish Experience of Two Dose Vaccination Programme Aiming at Eliminating Measles,

Mumps, and Rubella, 295 BRITISH MED. J. 1264 (1987), filed as Pet. Ex. 91.

27

U. Nieminen et al., Acute Thrombocytopenic Purpura Following Measles, Mumps and Rubella Vaccination. A

Report on 23 Patients, 82 ACTA PAEDIATR 267 (1993), filed as Pet. Ex. 92.

28

Frank A. Oski & J. Lawrence Naiman, Effect of Live Measles on the Platelet Count, 275 NEW ENGL. J. MED. 352

(1966), filed as Pet. Ex. 93.

29

Kathleen R. Stratton et al., Adverse Events Associated with Childhood Vaccines Other than Pertussis and Rubella,

271 JAMA 1602 (1994), filed as Pet. Ex. 94.

30

Paddy Farrington et al., A New Method for Active Surveillance of Adverse Events from Diphtheria/Tetanus/Pertussis

and Measles/Mumps/Rubella Vaccines, 345 THE LANCET 567 (1995), filed as Pet. Ex. 95.

31

Guidelines for the Investigation and Management of Idiopathic Thrombocytopenic Purpura in Adults, Children and

in Pregnancy, 120 BRITISH J. HAEMATOLOGY 574 (2003), filed as Pet. Ex. 38.

32

Douglas B. Cines et al., The ITP Syndrome: Pathogenic and Clinical Diversity, 113 BLOOD 6511 (2009), filed as

Pet. Ex. 42.

33

Dimitrios P. Bogdanos et al., Twin Studies in Autoimmune Disease: Genetics, Gender and Environment, 38 J.

AUTOIMMUNITY 156 (2012), filed as Pet. Ex. 96.

34

Dr. Gershwin did not actually cite any studies in support of these assertions.

35

Lisen Arnheim-Dahlstrom et al., Autoimmune, Neurological, and Venous Thromboembolic Adverse Events After

Immunisation of Adolescent Girls with Quadrivalent Human Papillomavirus in Denmark and Sweden: Cohort Study,

347 BRITISH MED. J. 1 (2013), filed as Pet. Ex. 101.

13

Dr. Forsthuber criticized Dr. Gershwin’s comparison of ITP induced by the MMR vaccine

and ITP induced by the HPV vaccine, highlighting the differences between the two vaccines. Resp.

Ex. A at 7. First, the MMR vaccine is an attenuated live virus containing three different viruses

while the HPV vaccine is made up of only recombinant (dead) HPV L1 viral proteins that are

incapable of replicating, unlike the MMR viruses. Id. (citing Resp. Ex. A2336 at 950). Second, the

MMR and HPV viruses are not related and therefore comparison between the viruses is

inappropriate as there is no evidence that the two vaccines can induce similar immune responses.

See id. d.at 7-8 (citing Resp. Ex. A2237 at 31-32; Resp. Ex. A2438 at 691-91) (“MMR vaccination

showed a low, but significant risk of ITP, whereas large vaccination studies have failed to show

any association of the HPV vaccine with autoimmune diseases, specifically ITP”). Dr. Forsthuber

further submitted that “molecular mimicry may be necessary, but not sufficient to induce human

autoimmune pathology and that other factors may be critical to induce pathology, such as

bystander activation or dual TCRs on T cells, or failure of immune regulation.” Resp. Ex. A at 4-

5 (citing Resp. Ex. A739 at 103; Resp. Ex. A840 at 105; Resp. Ex. A941 at 1098). However, Dr.

Forsthuber concluded that, “there is no doubt that even if significant molecular mimicry is

observed between a particular pathogen and human self-antigens it cannot be assumed de facto as

being causative for a human autoimmune disease condition . . .”. Id. Dr. Forsthuber also opined

that Dr. Gershwin’s argument of molecular mimicry as the appropriate mechanism present in this

case is highly speculative and not plausible. Id. Dr. Forsthuber ultimately concluded that the HPV

vaccine petitioner received on June 2, 2011 was not causally related to her ITP and that no specific

cause can be assigned to it. Id. at 10.

Dr. McKenzie added that Dr. Gershwin misstated the epidemiological studies referenced

in his report. Resp. Ex. B at 5. Specifically, there has been no documented association between the

HPV quadrivalent recombinant peptide antigen vaccination and ITP in the several studies that have

been performed. Id. (citing Resp. Ex. B442 at 404; Resp. Ex. B543 at 4-5). Dr. McKenzie further

36

Irja Davidkin et al., Persistence of Measles, Mumps, and Rubella Antibodies in an MMR-Vaccincated Cohort: A

20-Year Follow-up, 197 J. INFECTIOUS DISEASES 950 (2008), filed as Resp. Ex. A23.

37

Laura J. Sauve & David Scheifele, Do Childhood Vaccines Cause Thrombocytopenia, 14 PAEDIATRIC CHILD

HEALTH 31 (2009), filed as Resp. Ex. A22.

38

Eric K. France et al., Risk of Immune Thrombocytopenic Purpura After Measles-Mumps-Rubella Immunization in

Children, 121 PEDIATRICS 687 (2008), filed as Resp. Ex. A24.

39

Matthew F. Cusick et al., Molecular Mimicry as a Mechanism of Autoimmune Disease, 42 CLINIC REV. ALLERG.

IMMUNOL. 102 (2012), filed as Resp. Ex. A7.

40

Robert Root-Bernstein & DeLisa Fairweather, Unresolved Issues in Theories of Autoimmune Disease Using

Myocarditis as a Framework, 375 J. THEORETICAL BIOLOGY 101 (2015), filed as Resp. Ex. A8.

41

Jean-Marie Fourneau et al., Th Elusive Case for a Role of Mimicry in Autoimmune Diseases, 40 MOLECULAR

IMMUNOLOGY 1095 (2004), filed as Resp. Ex. A9.

42

Lamiae Grimaldi-Bensouda et al., Autoimmune Disorders and Quadrivalent Human Papillomavirus Vaccination of

Young Female Subjects, 275 J. INTNT’L MED. 398 (2014), filed as Resp. Ex. B4.

43

Lisen Arnheim-Dahlstrom et al., Autoimmune, Neurological, and Venous Thromboembolic Adverse Events After

Immunisation of Adolescent Girls with Quadrivalent Human Papillomavirus in Denmark and Sweden: Cohort Study,

14

opined that there are no biological studies that support Dr. Gershwin’s theory that the HPV vaccine

can cause ITP. Id. He also noted that the HPV vaccine is indicated for immunodeficient patients

in the 2015 Advisory Committee on Immunization Practices on behalf of the American Academy

of Pediatrics, the American Academy of Family Physicians, and the American College of

Obstetricians and Gynecologists. Id. Finally, Dr. McKenzie noted that, “Natural infections with

HPV have not been associated with ITP.” Id.

Dr. McKenzie submitted four significant studies in which it was determined that “those

that were given HPV vaccine were not at an increased risk of developing ITP following HPV

vaccinations.” See generally, Resp. Ex. B4, Resp. Ex. B5, Resp. Ex. C2,44 Resp. Ex. C3.45 He

provided two studies performed by Grimaldi-Bensouda which analyzed safety data related to HPV

administration from December 2007 through December 2014 in France. Resp. Ex. B4 at 402, 404;

Resp. Ex. C2 at 85. Both studies found no association between the HPV vaccination and ITP. See

id. Dr. McKenzie also submitted a study performed in Denmark and Sweden in which 296,826

women were studied from October 2006 through December 2010 looking for an increased

occurrence of autoimmune disorders, including ITP, following the HPV vaccine. Resp. Ex. B5 at

2. No increased rate of ITP was found. Id. He confirmed that “[n]o new biological studies to

establish a connection between the peptides in the HPV vaccine and ITP have been reported to

date.” Id. Dr. McKenzie further submitted a French study in which 2.2 million women were studied

post-HPV vaccination and no increased rate of ITP was found. Resp. Ex. C3 at 4763-65. This was

“the largest study evaluating the risk of [autoimmune disease] after HPV vaccination, thus

allowing the assessment of rare diseases not investigated previously.” Id. at 4766. Based on these

studies, respondent concluded, “Simply put, in terms of whether the HPV causes ITP, the scientific

community is not a field ‘bereft of science.’ Rather, a potential association between HPV and ITP

has been heavily researched, and no association has been found.” Resp. Response at 12.

Ultimately, Dr. Gershwin’s cursory assertions that the HPV vaccine can cause ITP via

molecular mimicry does not hold weight against Drs. Forsthuber and McKenzie’s explanations as

to why molecular mimicry is not a sufficient mechanism. Petitioner has failed to provide sound,

reliable evidence supporting a connection between ITP and the HPV vaccine; Dr. Gershwin has

only submitted generic articles discussing autoimmune disorders caused via molecular mimicry.

As noted by Dr. Forsthuber, “[Dr. Gershwin] has not adequately considered that the attenuated

viruses contained in the MMR vaccine are structurally and biologically unrelated to the HPV L1

particles contained in the Gardasil vaccine. Moreover, he has not provided any evidence for

sequence or structural homology between the MMR viruses and the Gardasil HPV L1 particles.”

Resp. Ex. A at 7. While Dr. Gershwin did provide evidence supporting a connection between the

MMR vaccine and ITP, he neglected to explain why the MMR and HPV vaccines are comparable

vaccinations in light of differences between the two highlighted by respondent’s experts.

Moreover, Dr. Gershwin relied on literature concluding that no evidence exists to support a

connection between the HPV vaccine and ITP, which was contrary to Dr. Gershwin’s assertions

347 BRITISH MED. J. 1 (2013), filed as Resp. Ex. B5. This study was also filed at Pet. Ex. 101.

44

Lamiae Grimaldi-Bensouda, Risk of Autoimmune Diseases and Human Papilloma Virus (HPV) Vaccines: Six Years

of Case-Reference Surveillance, 79 J. AUTOIMMUNITY 84 (2017), filed as Resp. Ex. C2.

45

Sara Miranda et al., Human Paillomavirus Vaccination and Risk Autoimmune Diseases: A Large Cohort Study of

Over 2 Million Young Girls in France, 35 VACCINE 4761 (2017), filed as Resp. Ex. C3.

15

that the HPV vaccine can cause ITP via molecular mimicry. Therefore, without any evidence

supporting a biologically sound and reliable mechanism, petitioner has failed to support her burden

under Althen prong I.

2. Lack of Logical Connection

The second Althen prong requires proof of a “logical sequence of cause and effect.”

Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1278). In other words, even if the

vaccinations can cause the injury, petitioner must show “that it did so in [this] particular case.”

Hodges v. Sec’y of Health & Human Servs., 9 F.3d 958, 962 n.4 (Fed. Cir. 1993) (citation omitted).

“A reputable medical or scientific explanation must support this logical sequence of cause and

effect,” id. at 961 (citation omitted), and “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,” Paluck v. Sec’y of Health & Human Servs., 786 F.3d 1373, 1385 (Fed. Cir.

2015) (quoting Andreu, 569 F.3d at 1375). Petitioner is not, however, required “to eliminate

alternative causes as part of establishing [their] prima facie case.” Doe v. Sec’y of Health & Human

Servs., 601 F.3d 1349, 1357-58 (Fed. Cir. 2010); see Walther v. Sec’y of Health & Human Servs.,

485 F.3d 1146, 1152 (Fed. Cir. 2007) (holding that a “petitioner does not bear the burden of

eliminating alternative independent potential causes”).

a. Petitioner likely had pre-existing ITP prior to her receipt of the allegedly

causal HPV vaccine.

Petitioner showed signs of ITP throughout the duration of her first pregnancy in 2007. She

had low platelet counts during all three trimesters and her platelet counts dropped as low as 44

k/ul. Pet. Ex. 9 at 1, 67, 73-75. Her first pregnancy ITP symptoms were inconsistent with traditional

gestational thrombocytopenia patients but instead appeared to be symptoms of ITP. See Pet. Ex. 2

at 168-28; Resp. Ex. A at 3 (citing Resp. Ex. A6 at 47). While petitioner did not have ITP

symptoms during her second pregnancy in 2009, she presented with a low platelet count, 100 k/ul

on October 20, 2009, when she was not pregnant, which is consistent with mild ITP. Resp. Ex. B

at 4 (citing Pet. Ex. 102, 105). Since no records were filed from 2010 and 2011 leading up to her

HPV vaccine, there is no proof that her platelet count was normal after 2009 or remained consistent

with mild ITP. Accordingly, both Drs. McKenzie and Forsthuber opined that it is likely petitioner

had preexisting ITP prior to her receipt of the HPV vaccine. Id.; Resp. Ex. D at 2.

Dr. Gershwin has not expressly refuted that petitioner had preexisting ITP, but opined that

petitioner’s history of ITP “would reflect her own genetic predisposition . . . [which] would make

her more susceptible to subsequent developments of thrombocytopenia.” Id. He further stated that

“the pathophysiology of ITP is essentially a promiscuous response against platelet antigens and,

as such, [she] would be expected to have memory cells against platelet antigens based on her

previous episode of ITP.” Resp. Ex. 20 at 10. Again, Dr. Gershwin neglected to provide evidence

in support of this assertion. See id. He referenced his original report in which he “emphasized the

role of molecular mimicry and cited the examples of the MMR vaccine.” Id. He also stated that if

any other clinically significant risk factors were identified, then he would have considered them in

his analysis (ignoring several risk factors identified below). Id.

16

In response to the foregoing, Dr. Forsthuber submitted that Dr. Gershwin clearly accepted

that petitioner had developed ITP prior to her allegedly causal HPV vaccine. Resp. Ex. D at 2

(citing Pet. Ex. 134 at 3). Dr. Forsthuber acknowledged that petitioner’s thrombocytopenia

symptoms during her first pregnancy were thought to be signs of GT, although ITP was never

definitively ruled out. Id. Additionally, Dr. Forsthuber explained that it is difficult to differentiate

between GT and pregnancy-induced ITP as there is no reliable laboratory testing to confirm the

diagnosis. Id. However, during petitioner’s first pregnancy, her platelet levels dropped as low as

41 k/ul, lower than what is expected from a patient with GT, whose platelet counts typically only

drop to 70 to 80 k/ul. Id. (citing Pet. Ex. 1 at 111). He also pointed out that petitioner’s platelet

count dropped abnormally low in October 2009, when she was not pregnant. Id. (citing Pet. Ex.

102 at 105, 132).

Petitioner clearly had low platelet counts when she was not pregnant before and after

receipt of the HPV vaccine, and during the first trimester of her pregnancies which is atypical for

gestational thrombocytopenia. Additionally, while some of petitioner’s treaters diagnosed her with

gestational thrombocytopenia, Dr. Forsthuber differentiated the symptoms of GT and petitioner’s

ITP, namely that petitioner’s platelet count dropped significantly lower than typical patients with

GT, and that her counts dropped earlier in her pregnancy than is typical of GT. Upon evaluation

of these facts, I find that petitioner more likely than not suffered from ITP prior to her receipt of

the HPV vaccine. This Court previously stated, “[P]etitioners must offer preponderant evidence

that an allegedly vaccine-caused illness began after receipt of the vaccination to demonstrate

entitlement to damages.” Johnson v. Sec’y of Health & Human Servs., No. 14-113V, 2017 WL

772534, at *18 (Fed. Cl. Spec. Mstr. Jan. 6, 2017). Accordingly, petitioner is not entitled to

compensation.

It is of note that a significant aggravation analysis may have been appropriate here if

petitioner had provided a sound and reliable mechanism for causation. See W.C. v. Sec’y of Health

& Human Servs., 704 F.3d 1352, 1357 (Fed. Cir. 2013) (“[A] petitioner in an off-table case must

show the vaccine actually caused the significant aggravation—not just that, accepting petitioner’s

medical theory as sound, the person’s condition worsened within a medically-acceptable

timeframe”). However, because petitioner failed to provide a sound and reliable mechanism for

causation and failed to provide any expert opinion of aggravation, that analysis is unnecessary.

b. Petitioner was experiencing several risk factors at the time of onset of

her ITP symptoms that are known causes of ITP.

Even if Dr. Gershwin had offered a sound and reliable mechanism of causation by which

petitioner’s ITP could have been caused by the HPV vaccine, several risk factors known to cause

ITP were present at the time of vaccination that Dr. Gershwin failed to acknowledge as potential

causes of petitioner’s ITP.46 Dr. Gershwin contended that petitioner was not affected by any

extrinsic unrelated factors that could have caused her ITP. Pet. Ex. 20 at 11. Dr. Gershwin was

alerted of the shortcomings in his reports by three orders of the Court giving him several

opportunities to remedy these issues. See Scheduling Orders, ECF Nos. 47, 57, 79. However, Dr.

46

Respondent asserted that he was not pleading alternative causes but pointed out that Dr. Gershwin flatly disregarding

petitioner’s medical history. See Resp. Response at 16, ECF No. 93.

17

Gershwin failed to take these opportunities to address the specific factors that petitioner was

experiencing before and during her pregnancy, including extreme stress, Gardnerella vaginalis,

HPV herpes warts, and the medication for those warts and ultimately concluded that there was no

evidence linking these factors and ITP. See Pet. Ex. 103 at 1-3; Pet. Ex. 134 at 1-2. Dr. Forsthuber

responded to these statements by identifying the following possible contributory factors. Resp. Ex.

A at 5.

i. Petitioner’s HPV and Aldera cream use at the time of vaccination

Petitioner had HPV genital warts on May 24, 2011 for which she was treated with Aldera

cream, approximately two weeks prior to her receipt of the HPV vaccine. Resp. Ex. D at 2 (citing

Pet. Ex. 1 at 64). Dr. Gershwin did not address petitioner’s actual HPV infection at the time of

vaccination, despite his assertions that HPV antigens in the vaccine can induce molecular mimicry

and cause ITP or differentiate between the HPV antigens petitioner had at the time of vaccination

because of her genital warts and those present in the HPV vaccination. Moreover, Dr. Gershwin

did not discuss the Aldera cream petitioner was prescribed to treat her genital warts, even though,

as Dr. Forsthuber asserted, the active ingredient of Aldera cream is Imiquimod. Imiquimod is a

Toll-like receptor (“TLR”) 7 agonist 4 that has been shown to “promote proinflammatory cytokine

production by macrophages from ITP patients, and to decrease platelet counts, i.e. promote

thrombocytopenia in an experimental mouse model of ITP.” Id. (citing Resp. Ex. D447 at 239). He

also indicated that at least one medical report has linked Imiquimod treatment as a cause ITP. Id.

(citing Resp. Ex. D548 at 79-80). Dr. Gershwin did not address petitioner’s Aldera cream usage

despite Dr. Forsthuber’s assertions. See generally Pet. Ex. 103, 134.

ii. Petitioner’s history of bacterial vaginosis with Gardnerella

In response to the Court’s inquiry as to the role of petitioner’s Gardnerella vaginalis as the

cause of her ITP, Dr. Gershwin cursorily stated, “Essentially, there is no evidence that Gardnerella

produces thrombocytopenia.” Pet. Ex.134 at 1. In response, Dr. Forsthuber opined, “[I]n many

patients, vaginal Gardnerella infection induces systemic immunoglobulin production; therefore, it

can generate a systemic immune response which could potentially induce autoantibodies and

autoreactive T cells via molecular mimicry.” Resp. Ex D at 1. Additionally, candida species, a

typical coinfection with vaginosis, have been associated with chronic ITP. Id. (citing Resp. Ex.

D349 at 202-03). Therefore, Dr. Forsthuber opined that petitioner’s Gardnerella and bacterial

vaginosis could have been contributing factors to petitioner’s ITP. Id.

47

Qing Yang et al., TLR7 Promotes Th1 Polarization in Immune Thrombocytopenia, 128 THROMBOSIS RESEARCH 237

(2011), filed as Resp. Ex. D4.

48

E.A. Whatling et al., Immune Thrombocytopenic Purpura: A Rare Side Effect in a Patient Treated with Imiquimod

for Lentigo Maligna, 13 JPRAS OPEN INTNT’L J. OPEN ACCESS J. OF SURGICAL RECONSTRUCTION 77 (2017), filed as

Resp. Ex. D5.

49

Mahmoud H. Ayesh et al., Candida Albicans-Induced Chronic Thrombocytopenic Purpura, 126 ACTA. HAEMATOL.

202 (2011), filed as Resp. Ex. D3.

18

iii. Petitioner’s pregnancy

ITP triggered by pregnancy typically appears in the first trimester as opposed to gestational

thrombocytopenia which occurs during the second and/or third trimester. Resp. Ex. A at 3 (citing

Resp. Ex. A5 at 397-98). As noted by petitioner’s hematologist, petitioner suffered from pregnancy

related ITP rather than gestational thrombocytopenia as her platelet counts dropped lower than 70

k/ul and onset of her symptoms occurred in the first trimester as opposed to later in her pregnancy.

See Pet. Ex. 2 at 125-28. Additionally, literature cited by Dr. Gershwin stated that “many

hematologic problems develop in pregnancy or can be triggered by the pregnant state,” and that

“pregnancy can exacerbate underlying hematologic disorders.” Id. at 9. Dr. Gershwin, however

opined that “[t]here is no known relationship between gestational ITP and [petitioner’s] subsequent

development of ITP.” Dr. Gershwin further opined that petitioner’s heavy bleeding during her

pregnancy would be consistent with thrombocytopenia but that, “It is not possible for [him] to

provide a percentage of contribution of the thrombocytopenia versus local placental factors and

the heavy bleeding that occurred during pregnancy.” Id. Dr. Gershwin disregarded blood work that

showed a low platelet count when she was not pregnant, which suggests that she had ITP prior to

this pregnancy.

Dr. Forsthuber explained that pregnancy alone can impact a woman’s immune system and

“represents a significant disturbance to the immune homeostasis and challenge to immune

tolerance mechanisms.” Resp. Ex. A at 6. He noted the first trimester is considered a

proinflammatory phase which could have increased petitioner’s risk of developing ITP during her

pregnancy. Id. (citing 14-15).

iv. Petitioner’s ongoing stress

When petitioner received the allegedly causal HPV vaccine, she admittedly was suffering

from a substantial amount of stress. She had just started a new job and had two other children with

serious medical issues. Pet. Ex. 16 at 63. She also presented to the emergency room within a week

of receiving the HPV after having been physically assaulted by an ex-boyfriend. Id. at 7-19, 59.

During this visit, several injuries were noted, and petitioner was reported to be especially anxious.

Id. at 9-10. She subsequently found out she was pregnant within two weeks of this emergency

department visit. Pet. Ex. 1 at 62, 81.

Dr. Gershwin denied that there is acceptable data that stress can trigger ITP or exacerbate

a person’s ITP symptoms. Pet. Ex. 134 at 2. Dr. Gershwin submitted that there has been no data

found associating individuals in combat zones with higher instances of ITP or other autoimmune

diseases. Id.

Dr. Forsthuber, however, argued that “[t]here is a vast amount of peer reviewed medical

literature implicating psychological stress in the development and modulation of a variety of

autoimmune conditions.” Resp. Ex. D at 3 (citing Resp. Ex. D650 at 365, 369-72). Specifically, Dr.

Forsthuber identified a study in which Iraq and Afghanistan veterans with post-traumatic stress

disorder have shown an elevated risk for autoimmune disorders, and thus petitioner’s stress related

50

Aoife O’Donovan et al., Elevated Risk for Autoimmune Disorders in Iraq and Afghanistan Veterans with

Posttraumatic Stress Disorder, 77 BIOLOGICAL PSYCHIATRY 365 (2015), filed as Resp. Ex. D6.

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to her domestic abuse, pregnancy, and children with health issues could have been a factor in her

development of ITP. Id. (citing 6).

v. Petitioner’s phentermine usage during pregnancy

Dr. Gershwin admitted that phentermine use during pregnancy is contraindicated but there

is little information available and thrombocytopenia is not listed as a side effect of the drug. Pet.

Ex. 132 at 1-2. He claimed to have researched phentermine side effects on the FDA website and

peer reviewed publications and found no such relationship between ITP and the drug. Id. Yet, he

cited to eHealthMe, a website, that stated “of 11,467 people reported to have side effects from

phentermine, 17, or .15%, had thrombocytopenia.” Id. at 1-2.

As phentermine is associated with several gastrointestinal side effects including

constipation and diarrhea, Dr. Forsthuber noted that petitioner’s prolonged use of this drug could

have affected her intestinal homeostasis and “thereby alter[ed] intestinal microbiota composition,

which, in turn, has moved to the forefront of interest in autoimmune research.” Resp. Ex. D at 2.

Dr. Forsthuber further stated that significant evidence in the autoimmunity research field has

suggested intestinal microbiota may trigger autoimmune disease pathology. Id. Therefore, he

concluded that petitioner’s phentermine usage could have “played a surreptitious role in

[petitioner’s] disease condition. Id.

Dr. McKenzie pointed out that Dr. Gershwin criticized respondent’s experts for identifying

risk factors without evidence that they could cause ITP, stating it was ironic that petitioner’s expert

did not apply the same logic to the HPV vaccine. Id. Dr. McKenzie concluded that out of the all

external factors both he and Dr. Forsthuber referenced as present in petitioner at the outset of her

ITP symptoms in 2011, including the HPV vaccine, the only event for which no epidemiologic or

scientific evidence exists is the vaccine. Id.

Petitioner presented with and suffered from a host of risk factors that could have

contributed to her preexisting ITP at the time of her HPV vaccine. Dr. Gershwin failed to address

any of these items; he also failed to provide any persuasive evidence that the HPV vaccine can

cause or aggravate ITP. While petitioner is not required to eliminate alternative causes to satisfy

prong II, her expert failed to address how the vaccine could have been the cause of or aggravated

her ITP in the first place while respondent provided evidence for each of the other illnesses and or

medication and their associations to ITP. See Pet. Ex. 20 at 11 (“During this time [approximately

one month prior to vaccination], there were no other risk factors identified . . .”).

Given petitioner’s likely pre-existing ITP and the several risk factors present before and at

the time of receipt of the allegedly causal vaccination, petitioner has failed to satisfy her burden

under Althen prong II.

3. Proximate Temporal Relationship

To satisfy the third Althen prong, petitioner must establish a “proximate temporal

relationship” between the vaccination and the alleged injury. Althen, 418 F.3d at 1281. This

“requires preponderant proof that the onset of symptoms occurred within a timeframe for which,

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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. Typically, “a petitioner’s failure to satisfy the

proximate temporal relationship prong is due to the fact that onset was too late after the

administration of a vaccine for the vaccine to be the cause.” Id. However, “cases in which onset is

too soon” also fail this prong; “in either case, the temporal relationship is not such that it is

medically acceptable to conclude that the vaccination and the injury are causally linked.” Id.; see

also Locane v. Sec’y of Health & Human Servs., 685 F.3d 1375, 1381 (Fed. Cir. 2012) (“[If] the

illness was present before the vaccine was administered, logically, the vaccine could not have

caused the illness.”).

As discussed above, there is considerable evidence that petitioner suffered from ITP prior

to vaccination. However, even if petitioner had proven that she did not have pre-existing ITP,

petitioner has provided no evidence of a medically acceptable timeframe for onset of ITP following

the HPV vaccine. Dr. Gershwin submitted evidence regarding a medically acceptable timeframe

for onset of ITP following an MMR vaccine, but provided no evidence as to whether the same

timeframe would be medically acceptable for the HPV vaccine. Accordingly, petitioner has also

failed to satisfy his burden under Althen prong III.

VI. Conclusion

Upon careful evaluation of all of the evidence submitted in this matter—including the

medical records, expert reports, and medical literature—I conclude that petitioner has not shown

by preponderant evidence that she is entitled to compensation under the Vaccine Act. Petitioner

has failed to offer sufficient evidence showing that the HPV vaccination caused her ITP. The

petition is therefore DISMISSED. The Clerk shall enter judgment accordingly.51

IT IS SO ORDERED.

s/ Mindy Michaels Roth

Mindy Michaels Roth

Special Master

51

Pursuant to Vaccine Rule 11(a), entry of judgment can be expedited by each party filing a notice renouncing the

right to seek review.

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