key: cord-1042625-2qsabbjv authors: Akiyama, Hiroaki; Kakiuchi, Seiji; Rikitake, Junpei; Matsuba, Hiroyuki; Sekinada, Daisuke; Kozuki, Yoko; Iwata, Nobuko title: Immune thrombocytopenia associated with Pfizer-BioNTech’s BNT162b2 mRNA COVID-19 vaccine date: 2021-08-04 journal: IDCases DOI: 10.1016/j.idcr.2021.e01245 sha: a853d1652afa3a6520bd6686f517c2f11c990753 doc_id: 1042625 cord_uid: 2qsabbjv The recent global pandemic of coronavirus disease 2019 (COVID-19) has led to vaccination in many parts of the world for herd immunity, and as vaccination has progressed, several rare adverse events have been reported. Immune thrombocytopenia (ITP) has been reported to be one of the rare adverse events caused by vaccination with MMR (measles-mumps-rubella) vaccine and influenza vaccine. In addition, ITP has been reported to occur in a small number of cases associated with the COVID-19 messenger ribonucleic acid (mRNA) vaccine. However, there are few reports on the details of the treatment and clinical course; optimal treatment has not yet been established. We report the case of a 20-year-old woman who developed ITP after receiving Pfizer-BioNTech’s BNT162b2 vaccine. She had generalized subcutaneous hemorrhage, 14 days after vaccination. At the time of our visit, she had marked thrombocytopenia and intraoral bleeding; she was diagnosed with ITP. Treatment with oral steroids was started and the platelet count promptly improved after 4 days of treatment. Since the response to treatment was very good, we tapered off the steroids. As these vaccines will be increasingly used in the future, it is important to recognize ITP as a possible adverse event. Immune thrombocytopenia (ITP) is an immune-mediated disorder that causes thrombocytopenia and bleeding. There are two types of ITP: primary and secondary. Secondary ITP is sometimes caused by infectious diseases, autoimmune diseases, vaccines, and other drugs [1] . In recent years, the global epidemic of coronavirus disease 2019 (COVID-19) has caused many deaths worldwide, and in response, vaccinations are being administered worldwide to provide herd immunity. In particular, messenger ribonucleic acid (mRNA) vaccines such as Pfizer-BioNTech's BNT162b2 and Moderna's mRNA-1273 have shown very positive results in clinical trials and are already being administered in many countries around the world [2, 3] . However, several adverse events that were not reported in the clinical trials have been recorded. Here, we report a case of secondary ITP that occurred after the first dose of the BNT162b2 mRNA vaccine. A 20-year-old Japanese woman presented with subcutaneous hemorrhage in her extremities and trunk, 12 days after receiving the BNT162b2 mRNA vaccine. Seventeen Blood tests showed that her white blood cell count and hemoglobin levels were within the reference values, while her platelet count was low (16,000/μL) and her immature platelet fraction was elevated to 11.9% (normal range 1.1-6.1%). No blasts appeared in the peripheral blood, and no significant findings were observed in other biochemical and coagulation tests, as shown in Table 1 . The Helicobacter pylori stool antigen test was negative. She had no drinking or smoking habits and had no medical or family history nor medications of note. The platelet count was within the reference level at the checkup performed 1 year and 6 months as well as 11 months prior, and no other abnormal findings were noted. Bone marrow aspiration revealed normocellular marrow with an increased number of megakaryocytes. We diagnosed ITP and administered prednisolone 50 mg/body weight (1 mg/kg). On day 4 after the start of treatment, the patient's platelet count improved to 210,000/μL, and the subcutaneous petechiae tended to disappear. On day 8, the platelet count was still within the reference value (153,000-343,000/μL) and the dose of prednisolone was reduced to 30 mg/body weight. Thereafter, the dose of prednisolone was tapered to 20 mg/body weight after 13 days, and the patient responded without relapse. Lee et al. also reported that symptoms of bleeding occurred between 1 and 23 days (median 5 days) after vaccine administration [8] . In the present case, bleeding symptoms occurred 14 days after the first dose of the vaccine, which is consistent with a previously reported course. ITP has been reported to be associated with various vaccinations such as the MMR vaccine, influenza vaccine, and polio vaccine [11] . The pathogenesis is presumed to be immune-mediated and is thought to be related to the increased B-cell function seen in primary ITP [12, 13] . Since mRNA vaccines have a different mode of action from conventional vaccines, it is unclear what mechanism causes the immune-mediated reaction. However, many patients, including the patient in this report, responded well to J o u r n a l P r e -p r o o f immunosuppressive therapy, suggesting that an immune-mediated mechanism may be involved. In this case, we administered 1 mg/kg of prednisolone as initial treatment as with primary ITP. The platelet count recovered to the reference level within a short period of 4 days. We assumed that this was vaccine-induced secondary ITP and rapidly reduced the dose. We avoided long-term steroid administration, as recommended for primary ITP. The platelet count remained normal after dose reduction. We encountered an extremely rare case of secondary ITP presumed to have occurred after BNT162b2 vaccination. Secondary ITP being a very rare complication, the optimal treatment has not yet been determined, and further case series will be necessary. On the other hand, the incidence of symptomatic thrombocytopenia after vaccination is much lower than the risk of death and morbidity due to SARS-CoV-2 infection, as stated in the Medical Advisory Board statement on the Platelet Disorder Support Association website [14] . The purpose of this case report is not to diminish the usefulness of vaccination or the well-documented safety profile of Pfizer-BioNTech's BNT16B2b2 mRNA vaccine. Author Contributions: HA and SK wrote the manuscript with support from all other J o u r n a l P r e -p r o o f The ITP syndrome: pathogenic and clinical diversity Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Secondary immune thrombocytopenia supposedly attributable to COVID-19 vaccination Immune Thrombocytopenia Following the Pfizer BioNTech BNT162b2 mRNA COVID-19 Vaccine Newly Diagnosed Idiopathic Thrombocytopenia Post COVID-19 Vaccine Administration Idiopathic thrombocytopenic purpura and the moderna Covid-19 vaccine Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination Immune thrombocytopenia following COVID-10. Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases B-cell hyperfunction in children with immune thrombocytopenic purpura persists after splenectomy Immune thrombocytopenic purpura risk by live, inactivated and simultaneous vaccinations among Japanese adults, children and infants: a matched case-control study Platelet Disorder Support Association. COVID-19 + ITP authors critically revised and approved the final version of the manuscript. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript. a Written informed consent was obtained from the patient for submission of the case report and an accompanying image. A copy of the written consent is available for review by the Editor-in-Chief ofthis journal on request.a