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\begin{document}

\title{Immune Thrombocytopenic Purpura After Receiving AstraZeneca Coronavirus
Disease-2019 Vaccine in A Patient with A Past History of the Same
Disease: A Case Report}



\author[1]{saba seyedi}%
\author[1]{Shadan Navid}%
\author[1]{zahra saadatian}%
\affil[1]{Gonabad University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 18, 2024}


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\textbf{Immune Thrombocytopenic Purpura After Receiving AstraZeneca
Coronavirus Disease-2019 Vaccine in A Patient with A Past History of the
Same Disease: A Case Report}

\textbf{Saba Seyedi\textsuperscript{a}, Shadan
Navid\textsuperscript{b},Zahra Saadatian\textsuperscript{c*}}

\begin{enumerate}
\tightlist
\item
  Department of Medical laboratory sciences, School of Medicine, Gonabad
  University of Medical Sciences, Gonabad, Iran.
\item
  Department of Anatomy, Faculty of Medicine, Social Determinants of
  Health Research Center, Gonabad University of Medical Science,
  Gonabad, Iran.
\item
  Department of Physiology, Faculty of Medicine, Infectious Diseases
  Research Center, Gonabad University of Medical Sciences, Gonabad,
  Iran.
\end{enumerate}

\textbf{Corresponding author: Zahra Saadatian.} Department of
Physiology, School of Medicine, Gonabad University of Medical Sciences,
Gonabad, Iran.

\emph{z.saadatian@yahoo.com}

\emph{saadatian.z@gmu.ac.ir}

key words: AstraZeneca, immune thrombocytopenic purpura, ChAdOx1
nCoV-19, AZD1222, case report, covid-19

\textbf{Immune Thrombocytopenic Purpura After Receiving AstraZeneca
Coronavirus Disease-2019 Vaccinein A Patient with A Past History of the
Same Disease: A Case Report}

\textbf{Key Clinical Message:} Immune thrombocytopenic purpura (ITP) is
an autoimmune disease characterized by a low platelets count, petechiae,
purpura, and conjunctival hemorrhage. In this paper, we present a
relapse of ITP in an Iranian 31-year-old woman as a potential
complication of the AstraZeneca vaccine.

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2)classified
in the coronaviridae family is characterized as a pandemic, and the
virus is spreading increasingly worldwide (1). Accelerated efforts to
develop safe and effective vaccines commenced immediately to control
this pandemic (2). AstraZeneca/Oxford's AZD1222, a vaccine candidate
that entered phase 1 clinical trial in mid-May 2020, was injected
intramuscularly in two doses to the participants aged 18-55 years at
least 28 days intervals (3). Early observations insinuate that exposure
to the AstraZeneca COVID-19 vaccine might trigger the expression of
antiplatelet antibodies, resulting in a condition with thrombocytopenia
and venous thrombotic events (e.g., intracranial venous sinus
thrombosis) (4). ITP is a rare autoimmune disorder with reduced
circulating platelets and occasionally impaired megakaryopoiesis (5).
Platelets, as the smallest cell fragments of the human blood, are
central players in the processes of hemostasis and thrombosis (6). The
normal human platelets count ranges from 150 \selectlanguage{ngerman}× 10\textsuperscript{9} to
450 × 10\textsuperscript{9}platelets per liter of blood, and its
insufficient count elevates the risk of spontaneous bleeding (7). In
this case report, we confer the relapse of immune thrombocytopenic
purpura after the first vaccination with ''the COVID-19 vaccine
AstraZeneca'' the first time.

Case history

An Iranian 31 years old female with a previous history of ITP presented
with progressive, vast, and diffuse ecchymosis, increased scattered
petechia purpura, and fatigue three weeks after receiving the first dose
of AstraZeneca. As a result of symptoms persistence, she was referred to
an outpatient laboratory to evaluate her complete blood count (CBC) 28
days after vaccine injection. CBC result showed a platelet count of
\&lt2000 / Mm\textsuperscript{3} and demonstrated ITP relapse.
Considering her previous medical history, she had experienced a platelet
decrease (9000/ Mm\textsuperscript{3} platelet count) when she was 25.
On that occasion, various tests including autoimmune diseases tests
(rheumatoid arthritis, lupus, and antiphospholipid syndrome), and bone
marrow aspiration had ruled out other causes of platelets decrease and
confirmed ITP. She had been treated with dexamethasone injection for
three days in the hospital and taking prednisolone pills for six months.
She had periodic checkups of CBCs, and the range of platelets was
different between 210-100×\selectlanguage{english} 10\textsuperscript{3}/ Mm\textsuperscript{3}.
The last CBC monitoring was carried out in 2019.

Differential diagnosis, investigations and treatment

After the COVID-19 pandemic, nevertheless, our case did not perform
routine checkups, nor did she have any symptoms of platelet depletion
such as scattered ecchymoses and fatigue before receiving the vaccine.
Since she previously had ITP, she was given high dose dexamethasone and
then saw a physician who recommended hospital admission when her
platelet count came back at 25000/ Mm\textsuperscript{3}. Other
hematological, biochemical, and immunological tests did not reveal any
other disease except intensive thrombocytopenia (Table 1).

In addition, her CRP was negative, and ESR was normal, ruling out any
infection and inflammation existence that could be related to other
causes of ITP. In the hospital, she received intravenous immunoglobulin
(IVIG)(50gr) and dexamethasone (40mg) for four days, and after her
platelet count reached above 100x\selectlanguage{english} 10\textsuperscript{3}/
Mm\textsuperscript{3}, she was discharged. On completion of treatment,
she had been prescribed 40mg per day of dexamethasone for four days at
intervals of two weeks with periodic monitoring of her CBC. Figure1
illustrates platelet counts considering before and after disease
diagnosis and treatment.

Outcome and follow-up

Considering the persistence of platelet count in the normal range and
with due attention to the previous finding that expresses the benefit of
vaccination is more than its risks (8), our case received the next dose
of AstraZeneca vaccine three months after the first dose and about 1.5
months after treatment completion. Nevertheless, her platelet stability
did not collapse (210x\selectlanguage{english} 10\textsuperscript{3}/ Mm\textsuperscript{3}),
nor did she present signs of ITP. Moreover, she got vaccinated with the
same vaccine for the third time about six months later and she did not
experience any side effects (platelet count: 213x\selectlanguage{english} 10\textsuperscript{3}/
Mm\textsuperscript{3}).

Discussion

Immune thrombocytopenic purpura is an autoimmune blood disorder
characterized by platelet reduction followed by petechiae, purpura,
conjunctival hemorrhage, or other types of mucocutaneous bleeding (9).
The incidence of the disorder is about 100 in 1milion people each year,
and most of the patients are children (9). However, it is developed in
acute form lasting about six months in children and adults. It is
generally chronic and occurs more in women than men (9). Early detection
of ITP is critical because intracranial hemorrhage could be the major
cause of fatal bleeding in these patients (9). Immune thrombocytopenic
purpura usually appears following autoimmune conditions and viral
infections (6). In addition, considering many reports, ITP could be
manifested as a result of vaccines (6).

More than 100 COVID-19 vaccine candidates are currently under
development, and the number is increasing (10). Various types of
vaccines are classified into recombinant protein vaccines, mRNA-based
vaccines, DNA- based vaccines, and vector-based vaccines (10). The
AstraZeneca vaccine is from the adenovirus category, and the vaccine
candidate is ChAdOx1 nCoV-19 (10). The advantages of this vaccine are a
high transfection efficacy, as the viral vector imitates the natural
infection process. Disadvantages are that the vaccine may promote
thrombocytopenia and intracranial venous sinus thrombosis (4). In
addition, there are some reports of post vaccine ITP (11).

Previously, Koch and his colleagues described a 41 years old male with
ITP, 14 days after the first dose of vaccination with AstraZeneca from
Germany (5). Furthermore, there were other reports of ITP three and two
days after receiving AstraZeneca in a Korean 66 years old female and an
Iraqi 25 years old male respectively (16, 17). In a case series, 17
cases were reported with secondary ITP related to AstraZeneca. All of
them had onset within 28 days after vaccine administration, but one case
diagnosed with ITP after 78 days (11).

According to the information from previous vaccines, various mechanisms
could trigger ITP after vaccination, such as impairment regulation of T
cells, elevated pro-inflammatory cytokine production, and increased
macrophage-mediated eradication (12).~Although the mechanism of
vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)
post-AstraZeneca vaccine has been elucidated in some research (13),
there isn't much known about the mechanism of immune thrombocytopenia
post-AstraZeneca vaccine. It seems IgG antibodies against platelet
factor 4 (PF4) are responsible for VITT (14). On the other hand, IgG is
the principal antibody in ITP, which is opposed to platelet membrane
glycoproteins such as GPIIb/IIIa (15). Moreover, spike protein is the
antigenic target for vaccines such as SARS-CoV-1 and MERS (15). But it's
unclear whether spike protein and the PF4 have any cross-reactions with
each other (15). Altogether, more information is required to determine
if the underlying mechanism of other vaccines can be the same as
post-COVID19 vaccine ITP.

In this paper we introduced an Iranian 31 years old female with a past
history of ITP who developed petechia purpura and ecchymosis following
AstraZeneca first dose administration and diagnosed with
thrombocytopenia. After completion of treatment the next doses of the
same vaccine are injected and there were no side effects. To the best of
our knowledge, this paper may be the first case report presenting a
patient with a past history of vaccine complication receiving the second
and booster doses of the same vaccine without any incident.

Conclusion

Some patients with past history of ITP may be more susceptible to immune
thrombocytopenia from drugs or inciting agents as well as AstraZeneca
Coronavirus Disease-2019 Vaccine. Physicians should always be cautious
administering new agents to ITP patients since that disorder, a prior
indicated altered immune response. In addition, measuring platelet count
before and after vaccine reception is suggested. Furthermore, it is
indispensable to pay attention to any early signs of ITP to primarily
manage the condition and prevent disease deterioration that could be
life-threatening.

Declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of the Infectious
Diseases Center, Gonabad University of Medical Sciences, Gonabad, Iran.
(IR.GMU.REC.1400.207).

Author contributions

Saba Seyedi: Conceptualization, Writing -- original draft

Shadan Navid: investigation, data curation

Zahra Saadatian: Supervision, writing -- review and editing

Acknowledgements

We would like to thank the patient for agreeing to share her clinical
information with the readers of this article.

Funding information

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

All authors have approved the manuscript for submission and have no
competing interests to declare.

Consent

Written informed consent was obtained from the patient for publication
of this case report.

Availability of data and material

Not applicable

References

1. Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and
COVID-19. Nature Reviews Microbiology. 2021;19(3):141-54.

2. Heath P, Galiza E, Baxter D, Boffito M, Browne D, Burns F, et al.
Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. The New England
journal of medicine. 2021;385.

3. Sharma O, Sultan AA, Ding H, Triggle CR. A Review of the Progress and
Challenges of Developing a Vaccine for COVID-19. Front Immunol.
2020;11:585354.

4. Wolf ME, Luz B, Niehaus L, Bhogal P, Bazner H, Henkes H.
Thrombocytopenia and Intracranial Venous Sinus Thrombosis after
''COVID-19 Vaccine AstraZeneca'' Exposure. J Clin Med. 2021;10(8).

5. Koch M, Fuld S, Middeke JM, Fantana J, von Bonin S, Beyer-Westendorf
J. Secondary Immune Thrombocytopenia (ITP) Associated with ChAdOx1
Covid-19 Vaccination - A Case Report. TH Open. 2021;5(3):e315-e8.

6. Idogun PO, Ward MC, Teklie Y, Wiese-Rometsch W, Baker J. Newly
Diagnosed Idiopathic Thrombocytopenia Post COVID-19 Vaccine
Administration. Cureus. 2021;13(5):e14853.

7. Msaouel P, Lam AP, Gundabolu K, Chrysofakis G, Yu Y, Mantzaris I, et
al. Abnormal platelet count is an independent predictor of mortality in
the elderly and is influenced by ethnicity. Haematologica.
2014;99(5):930.

8. Simpson CR, Shi T, Vasileiou E, Katikireddi SV, Kerr S, Moore E, et
al. First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and
thrombocytopenic, thromboembolic and hemorrhagic events in Scotland. Nat
Med. 2021;27(7):1290-7.

9. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J
Med. 2002;346(13):995-1008.

10. Wang J, Peng Y, Xu H, Cui Z, Williams RO, 3rd. The COVID-19 Vaccine
Race: Challenges and Opportunities in Vaccine Formulation. AAPS
PharmSciTech. 2020;21(6):225-.

11. Gordon SF, Clothier HJ, Morgan H, Buttery JP, Phuong LK, Monagle P,
et al. Immune thrombocytopenia following immunisation with Vaxzevria
ChadOx1-S (AstraZeneca) vaccine, Victoria, Australia. Vaccine.
2021;39(48):7052-7.

12. Perricone C, Ceccarelli F, Nesher G, Borella E, Odeh Q, Conti F, et
al. Immune thrombocytopenic purpura (ITP) associated with vaccinations:
a review of reported cases. Immunol Res. 2014;60(2-3):226-35.

13. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger
S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl
J Med. 2021;384(22):2092-101.

14. Schultz NH, Sorvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F,
Ahlen MT, et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19
Vaccination. N Engl J Med. 2021;384(22):2124-30.

15. A Ali E, Al-Maharmeh Q, Rozi WM, Habib MB, Yassin M. Immune
thrombocytopenia purpura flare post COVID-19 vaccine. Ann Med Surg
(Lond). 2022;75:103164-.

16. Kim G, Choi EJ, Park HS, Lee JH, Lee JH, Lee KH. A Case Report of
Immune Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. J Korean Med
Sci. 2021;36(43):e306.

17. Razzaq AK, Al-Jasim A. Oxford-AstraZeneca Coronavirus Disease-2019
Vaccine-Induced Immune Thrombocytopenia on Day Two. Case Reports in
Hematology. 2021;2021:2580832.

FIGURE1: platelet count x 10 \textsuperscript{3}/ Mm\textsuperscript{3}
based on test date.

Vertical axis denotes platelet count and normal range of platelet is
over than 150x\selectlanguage{english} 10\textsuperscript{3}/ Mm\textsuperscript{3}. Horizontal
axis denotes the date that the tests were performed.

TABLE1: Results of clinical laboratory tests after first spontaneous
intravenous injection of dexamethasone 40 mg

\textbf{Hematology} Test CBC\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Test & Result & Reference Value/Unit\tabularnewline
WBC & 11400 & 4000-11000/Mm\textsuperscript{3}\tabularnewline
Neutrophils & 10400 & 3000-5800/Mm\textsuperscript{3}\tabularnewline
Lymphocytes & 700 & 1500-3000/Mm\textsuperscript{3}\tabularnewline
Platelet & 25000 & 150,000-400,000/Mm\textsuperscript{3}\tabularnewline
RBC & 4.62 & 4-5.1/Mm\textsuperscript{3}\tabularnewline
Hb & 14.0 & 12.0-16.0/Mg/dl\tabularnewline
HCT & 40.5 & 34-44/\%\tabularnewline
MCV & 87.8 & 80-96/fl\tabularnewline
MCH & 30.3 & 27-33/pg\tabularnewline
MCHC & 34.6 & 32-36/g/dl\tabularnewline
ESR 1\textsuperscript{st} hr & 9 & 0-20/mm/h\tabularnewline
\textbf{PT} & &\tabularnewline
\textbf{PT patient} & 14.2 & second\tabularnewline
\textbf{PT Control time} & 12.3 & second\tabularnewline
INR & 1.16 &\tabularnewline
PTT & 30.2 & 27-45/second\tabularnewline
\textbf{Biochemistry} Test & \textbf{Biochemistry} Test &
\textbf{Biochemistry} Test\tabularnewline
Blood Biochemistry & Result & Reference Value/Unit\tabularnewline
BUN & 16 & 7-21/mg/dl\tabularnewline
Creatinine & 0.61 & 0.6-1.2/mg/dl\tabularnewline
Na & 133 & 40-220/mEq/L\tabularnewline
K & 3.7 & 3.5-5/mEq/L\tabularnewline
Ca & 8.9 & 8-11/mg/dl\tabularnewline
Bilirubin Total & 0.99 & 1.0-10.5/mg/dl\tabularnewline
Bilirubin Direct & 0.25 & 0.1-0.3/mg/dl\tabularnewline
AST & 46 & 15-46/U/L\tabularnewline
ALT & 43 & 8-45/U/L\tabularnewline
ALP & 280 & 64-306/U/L\tabularnewline
ALB & 4.54 & 3.5-5.2/g/dL\tabularnewline
\textbf{Immunology} Test & \textbf{Immunology} Test &
\textbf{Immunology} Test\tabularnewline
Serology & Result & Reference Value\tabularnewline
CRP & Negative & Negative\tabularnewline
\bottomrule
\end{longtable}

WBC: white blood cells; RBC: red blood cells; Hb: hemoglobin; HCT:
hematocrit; MCV: mean corpuscular volume; MCH: mean corpuscular
hemoglobin; MCHC: mean corpuscular hemoglobin concentration;
ESR1\textsuperscript{st} hr: erythrocyte sedimentation rate first hour;
PT: prothrombin time; INR: international normalized ratio; PTT: partial
thromboplastin time; BUN: blood urea nitrogen; AST: aspartate
aminotransferase; ALT: alanine aminotransferase; ALP: Alkaline
phosphatase; ALB: albumin CRP: c-reactive protein

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