key: cord-0723304-3a52nptt authors: Vorster, Luna; Kirk, Susan E.; Muscal, Eyal; Despotovic, Jenny M.; Cohen, Clay T.; Sartain, Sarah E. title: COVID‐19 vaccine (mRNA BNT162b2) and COVID‐19 infection‐induced thrombotic thrombocytopenic purpura in adolescents date: 2022-04-04 journal: Pediatr Blood Cancer DOI: 10.1002/pbc.29681 sha: 3edd1496ae4b64e12a6676286fe636a94bab27c5 doc_id: 723304 cord_uid: 3a52nptt The mRNA COVID‐19 vaccine and COVID‐19 infection caused by the SARS‐CoV‐2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID‐19 vaccination or infection in pediatric or adolescent patients. We describe three adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID‐19 vaccine or after COVID‐19 infection. Our observations demonstrate that the Pfizer‐BioNTech mRNA vaccine and COVID‐19 infection can act as triggers for the development/relapse of both congenital and acquired TTP. The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of both acquired and congenital thrombotic thrombocytopenic purpura (TTP). We present a case series of adolescents presenting with TTP (including both de novo and relapsed disease) following administration of the Pfizer-BioNTech mRNA BNT162b2 anti-COVID-19 vaccine or after COVID-19 infection. Patients were identified through presentation to Texas Children's Hos- Our In the case of inherited TTP, Galbusera and colleagues address a "two hit model," highlighting cases in which patients with ADAMTS13 mutations manifest TTP after an infection or pregnancy. 16, 17 Mouse models of ADAMTS13 deficiency suggest an environmental trigger may be needed in addition to a gene mutation to fully manifest TTP, with ADAMTS13-deficient mice developing TTP after the introduction of Shiga toxin. 18 These studies imply that an immunologic event, such as an infection or vaccination, triggers inherited TTP. reports of TTP, and five of those were in patients <21 years old. 23 Of note, the VAERS data may not be entirely accurate, as some cases may not have been reported and the search criteria may not have included all TTP cases. As we show, COVID-19 infection itself can also trigger TTP, among many other severe and devastating consequences, and therefore, we continue to stress that the benefits of the vaccine outweigh the risks, especially with the development of new, more transmissible, and potentially virulent SARS-CoV-2 variants. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates Successful treatment of congenital TTP with a novel approach using plasma-derived factor VIII First report of a de novo iTTP episode associated with an mRNA-based anti-COVID-19 vaccination Relapse of thrombotic thrombocytopenic purpura after COVID-19 vaccine Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines Perspectives on vaccine induced thrombotic thrombocytopenia Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination Exacerbation of immune thrombocytopenia following COVID-19 vaccination Immune thrombocytopenic purpura after vaccination with COVID-19 vaccine (ChAdOx1 nCov-19) Thrombotic thrombocytopenic purpura: a new menace after COVID bnt162b2 vaccine A case of COVID-19 induced thrombotic thrombocytopenic purpura Influenza a infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor COVID-19 and autoimmune diseases Guillain Barre syndrome associated with COVID-19 infection: a case report Systemic infections mimicking thrombotic thrombocytopenic purpura Inherited thrombotic thrombocytopenic purpura The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice Do COVID-19 RNA-based vaccines put at risk of immunemediated diseases? In reply to "potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases COVID-19 vaccines induce severe hemolysis in paroxysmal nocturnal hemoglobinuria Public Health Service (PHS), Centers for Disease Control (CDC) /Food and Drug Administration (FDA), Vaccine Adverse Event Reporting System (VAERS) 1990 -01/14/2022 COVID-19 vaccine (mRNA BNT162b2) and COVID-19 infection-induced thrombotic thrombocytopenic purpura in adolescents The authors declare that there is no conflict of interest.