Immune Thrombocytopenic Purpura After Receiving AstraZeneca Coronavirus Disease-2019 Vaccine in A Patient with A Past History of the Same Disease: A Case ReportSaba Seyedia, Shadan Navidb,Zahra Saadatianc*Department of Medical laboratory sciences, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.Department of Anatomy, Faculty of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Science, Gonabad, Iran.Department of Physiology, Faculty of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.Corresponding author: Zahra Saadatian. Department of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, [email protected]@gmu.ac.irkey words: AstraZeneca, immune thrombocytopenic purpura, ChAdOx1 nCoV-19, AZD1222, case report, covid-19Immune Thrombocytopenic Purpura After Receiving AstraZeneca Coronavirus Disease-2019 Vaccinein A Patient with A Past History of the Same Disease: A Case ReportKey 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.IntroductionSevere 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 × 109 to 450 × 109platelets 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 historyAn 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 / Mm3 and demonstrated ITP relapse. Considering her previous medical history, she had experienced a platelet decrease (9000/ Mm3 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× 103/ Mm3. The last CBC monitoring was carried out in 2019.Differential diagnosis, investigations and treatmentAfter 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/ Mm3. 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 100× 103/ Mm3, 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-upConsidering 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 (210× 103/ Mm3), 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: 213× 103/ Mm3).DiscussionImmune 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.ConclusionSome 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.DeclarationsEthics approval and consent to participateThis 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 contributionsSaba Seyedi: Conceptualization, Writing – original draftShadan Navid: investigation, data curationZahra Saadatian: Supervision, writing – review and editingAcknowledgementsWe would like to thank the patient for agreeing to share her clinical information with the readers of this article.Funding informationThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflict of interest statementAll authors have approved the manuscript for submission and have no competing interests to declare.ConsentWritten informed consent was obtained from the patient for publication of this case report.Availability of data and materialNot applicableReferences1. 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, Sørvoll 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.