Year: 2022
Type: article
Abstract: BACKGROUND: COVID-19 vaccines have been associated with a rare thrombotic and thrombocytopenic reaction, Vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by platelet-activating anti-PF4 antibodies. This study sought to assess clonality of VITT antibodies and evaluate their characteristics in antigen-based and functional platelet studies. METHODS: Anti-PF4 antibodies were isolated from five patients with VITT secondary to ChAdOx1 nCoV-19 (n=1) or Ad26.COV2.S (n=4) vaccination. For comparative studies with heparin-induced thrombocytopenia (HIT), anti-PF4 antibodies were isolated from one patient with spontaneous HIT, another with "classical" HIT, and two patients with non-pathogenic (non-platelet activating) anti-PF4 antibodies. Isolated antibodies were subject to ELISA and functional testing, and mass spectrometric evaluation for clonality determination. RESULTS: All five VITT patients had oligoclonal anti-PF4 antibodies (3 monoclonal, one bi- and one tri-clonal antibodies), while HIT anti-PF4 antibodies were polyclonal. Notably, like VITT antibodies, anti-PF4 antibodies from a spontaneous HIT patient were monoclonal. The techniques employed did not detect non-pathogenic anti-PF4 antibodies. The ChAdOx1 nCoV-19-associated VITT patient made an excellent recovery with heparin treatment. In vitro studies demonstrated strong inhibition of VITT antibody-induced platelet activation with therapeutic concentrations of heparin in this and one Ad26.COV2.S-associated VITT patient. Oligoclonal VITT antibodies with persistent platelet-activating potential were detected at 6 and 10 weeks after acute presentation in two patients tested. Two of the 5 VITT patients had recurrence of thrombocytopenia and one patient had focal seizures several weeks after acute presentation. CONCLUSION: Oligoclonal anti-PF4 antibodies mediate VITT. Heparin use in VITT needs to be further studied.
Source: Blood
Institutions: Mayo Clinic, University Hospital Augsburg, University of Colorado Anschutz, University of Utah, University of Utah Health Care, ARUP Institute for Clinical and Experimental Pathology, University of Maryland, Baltimore, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Versiti Blood Center of Wisconsin, Versiti Blood Research Institute Foundation
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1371740071, G1739079635, G2212411376, New Approaches to Pathogenesis and Diagnosis of Heparin-Induced, B cell responses in heparin-induced thrombocytopenia, G8665207574, New approaches to the pathophysiology, diagnosis and management of heparin-induced thrombocytopenia, Molecular Basis of the Humoral Immune Response in Heparin-Induced Thrombocytopenia, B-cell response and thrombotic complications in COVID-19
OpenAlex ID: W4280567542