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Pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT).
Greinacher, Andreas; Schönborn, Linda; Siegerist, Florian; Steil, Leif; Palankar, Raghavendra; Handtke, Stefan; Reder, Alexander; Thiele, Thomas; Aurich, Konstanze; Methling, Karen; Lalk, Michael; Völker, Uwe; Endlich, Nicole.
  • Greinacher A; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address: andreas.greinacher@med.uni-greifswald.de.
  • Schönborn L; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Siegerist F; Institute for Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
  • Steil L; Interfaculty Institute of Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Palankar R; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Handtke S; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Reder A; Interfaculty Institute of Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Thiele T; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Aurich K; Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Methling K; Institute of Biochemistry, University of Greifswald, Greifswald, Germany.
  • Lalk M; Institute of Biochemistry, University of Greifswald, Greifswald, Germany.
  • Völker U; Interfaculty Institute of Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Endlich N; Institute for Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
Semin Hematol ; 59(2): 97-107, 2022 04.
Article in English | MEDLINE | ID: covidwho-1768934
ABSTRACT
Vaccine-induced immune thrombotic thrombocytopenia (VITT; synonym, thrombosis with thrombocytopenia syndrome, is associated with high-titer immunoglobulin G antibodies directed against platelet factor 4 (PF4). These antibodies activate platelets via platelet FcγIIa receptors, with platelet activation greatly enhanced by PF4. Here we summarize the current concepts in the pathogenesis of VITT. We first address parallels between heparin-induced thrombocytopenia and VITT, and provide recent findings on binding of PF4 to adenovirus particles and non-assembled adenovirus proteins in the 2 adenovirus vector-based COVID-19 vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S. Further, we discuss the potential role of vaccine constituents such as glycosaminoglycans, EDTA, polysorbate 80, human cell-line proteins and nucleotides as potential binding partners of PF4. The immune response towards PF4 in VITT is likely triggered by a proinflammatory milieu. Human cell-line proteins, non-assembled virus proteins, and potentially EDTA may contribute to the proinflammatory state. The transient nature of the immune response towards PF4 in VITT makes it likely that-as in heparin-induced thrombocytopenia -marginal zone B cells are key for antibody production. Once high-titer anti-PF4 antibodies have been formed 5 to 20 days after vaccination, they activate platelets and granulocytes. Activated granulocytes undergo NETosis and the released DNA also forms complexes with PF4, which fuels the Fcγ receptor-dependent cell activation process, ultimately leading to massive thrombin generation. Finally, we summarize our initial observations indicating that VITT-like antibodies might also be present in rare patients with recurrent venous and arterial thrombotic complications, independent of vaccination.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Purpura, Thrombocytopenic, Idiopathic / COVID-19 Vaccines / COVID-19 Type of study: Etiology study Topics: Vaccines Limits: Humans Language: English Journal: Semin Hematol Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Purpura, Thrombocytopenic, Idiopathic / COVID-19 Vaccines / COVID-19 Type of study: Etiology study Topics: Vaccines Limits: Humans Language: English Journal: Semin Hematol Year: 2022 Document Type: Article