Thrombotic thrombocytopenic purpura temporally associated with BNT162b2 vaccination in an adolescent successfully treated with caplacizumab

Kirpalani, Amrit; Garabon, Justin J W; Amos, Kiersten; Patel, Serina; Sharma, Ajay P.; Ganesan, Saptharishi Lalgudi; Barton, Michelle Henry; Cacciotti, Chantel; Leppington, Sarah; Bakovic, Linda; Huang, Shih‐Han S.; Knauer, Michael J.; Tole, Soumitra

doi:10.1111/bjh.17782

Cited by 27 publications

(26 citation statements)

References 16 publications

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“…Globally, during the last 50 years only a few cases of TTP have been documented for influenza vaccines (Table 3) (139), even though 3100 million seasonal influenza vaccine doses have been administered in the United States of America alone since 1980 (140). A similar remark can be made of COVID vaccines, where, at the time of writing, only 2 cases of relapsing iTTP (134,135) and 8 de novo iTTP cases (136)(137)(138)141) were identified, among many millions of doses administered currently in the world. In this context, it is important not to confuse iTTP with vaccineinduced thrombotic thrombocytopenia (VITT), which has different mechanisms compared to iTTP (142,143).…”

Section: Some Reports Described An Association Between Vaccine Administration and Development Of Ittp (Examples Listed Inmentioning

confidence: 91%

Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura

2021

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Immune thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder of which the etiology is not fully understood. Autoantibodies targeting ADAMTS13 in iTTP patients have extensively been studied, the immunological mechanisms leading to the breach of tolerance remain to be uncovered. This review addresses the current knowledge on genetic factors associated with the development of iTTP and the interplay between the patient’s immune system and environmental factors in the induction of autoimmunity against ADAMTS13. HLA-DRB1*11 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB1*08:03 was recently identified as a risk factor in the Japanese population. Combined in vitro and in silico MHC class II peptide presentation approaches suggest that an ADAMTS13-derived peptide may bind to both HLA-DRB1*11 and HLA-DRB1*08:03 through different anchor-residues. It is apparent that iTTP is associated with the presence of infectious microorganisms, viruses being the most widely associated with development of iTTP. Infections may potentially lead to loss of tolerance resulting in the shift from immune homeostasis to autoimmunity. In the model we propose in this review, infections disrupt the epithelial barriers in the gut or lung, promoting exposure of antigen presenting cells in the mucosa-associated lymphoid tissue to the microorganisms. This may result in breach of tolerance through the presentation of microorganism-derived peptides that are homologous to ADAMTS13 on risk alleles for iTTP.

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Section: Some Reports Described An Association Between Vaccine Administration and Development Of Ittp (Examples Listed Inmentioning

confidence: 91%

Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura

2021

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“…In a few cases, an absence of PF-4 antibody further helped to refute the diagnosis of VITT. Moreover, the studies reporting high titers of SARS-CoV-2-IgG post-vaccination may also potentiate the hypothesis of vaccine-related TTP [22] . Notably, causality could not be assigned through this qualitative analysis, and whether these are just coincidental associations cannot be accurately judged.…”

Section: Discussionmentioning

confidence: 97%

Thrombotic thrombocytopenic purpura (TTP) after COVID-19 vaccination: A systematic review of reported cases

Saluja

Gautam

Yadala

et al. 2022

Thrombosis Research

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“…There are 16 cases of ITP, 12 cases of TTP reactivation, 11 cases of suspected intracerebral hemorrhage (ICH), 6 cases of cerebral venous sinus thrombosis, 1 case of pulmonary embolism, 1 case of renal thrombotic microangiopathy, a case of ST-elevation myocardial infarction (STEMI), 1 case of stroke, 1 case of central retinal artery occlusion, and a case of lower limb DVT associated with BNT162b2( Fig. 1 ) [ [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] ]. The STEMI reported in an elderly gentleman with multiple cardiovascular and pro-thrombotic risk factors 30mins post first dose of BNT162b2 is attributed to vaccination-induced “Kounis syndrome” or allergic myocardial infarction likely secondary to mast cell activation from an allergic or anaphylactoid reaction [ 11 ].…”

Section: Discussionmentioning

confidence: 99%