key: cord-0849303-sfqpyu44
authors: Althaus, Karina; Zlamal, Jan; Bakchoul, Tamam
title: Antibody‐mediated platelet activation in COVID‐19: A coincidence or a new mechanism of the dysregulated coagulation system?
date: 2021-04-20
journal: J Thromb Haemost
DOI: 10.1111/jth.15275
sha: 13c19a6925891104870b91ec7548455404786ebc
doc_id: 849303
cord_uid: sfqpyu44

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In this issue of JTH, Nazy and colleagues report on antibodymediated platelet activation as a driver of thrombosis in coronavirus disease 2019 (COVID-19) infection. 1 During the pandemic, and despite the lockdown, the authors made use of a routine assay that uses washed platelets to investigate antibody-mediated platelet activation. They found that sera from critically ill COVID-19 patients have the ability to activate platelets via crosslinking their Fc-gamma (y)-receptor (R) IIa.

Although there are enormous numbers of publications on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the mystery of high incidences of micro-and macrovascular thromboembolic events despite anticoagulant therapy in critically ill COVID-19 patients remains unsolved. Interestingly, because COVID-19 is occasionally accompanied by thrombocytopenia, the thrombotic phenotype shows some similarity with heparin-induced thrombocytopenia (HIT). 2, 3 In fact, SARS-CoV-2 infection has been described to be associated with platelet hyperreactivity, which may contribute to thromboembolic complications in COVID-19. 4 Consequently, the authors followed the idea to explore the role of phosphatidylserine. Most importantly, we observed that sera from these patients are able to induce a procoagulant phenotype in platelets from healthy donors. We showed that IgG from patients with severe COVID-19 triggers the formation of procoagulant platelets via FcγRIIa. 6 This mechanism is also induced by ICs and not only by an antibody-mediated pathway. ICs are known to trigger endothelial cell activation in HIT and in lupus vasculitis. 7, 8 For future experiments, it would be interesting to differentiate between IgG antibodies specific against platelets (as previously reported for Dengue infections 9 ) and

circulating ICs that activate platelets in lupus. 10 This can be easily done by testing purified IgG fractions from patient's sera or treating sera by polyethylene glycol to remove unspecific immune complexes.

Awaiting the results from these studies, the observations of Nazy et al. and our recent study indicate an important aspect of antibodymediated platelet activation in the thromboinflammation during infection diseases such as, but not limited to, This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Second, the safety of convalescent plasma from noncritically ill COVID-19 subjects was a concern of this study and others. 6 

The authors have no conflict of interest. 

Platelet-activating immune complexes identified in critically ill COVID-19 patients suspected of heparin-induced thrombocytopenia. JTH. 2021. Online ahead of print

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis

A 14-year study of heparin-induced thrombocytopenia

Platelet gene expression and function in patients with COVID-19

Influenza virus H1N1 activates platelets through FcgammaRIIA signaling and thrombin generation

Antibody-induced procoagulant platelets in severe COVID-19 infection

Anti-platelet factor 4/heparin antibodies from patients with heparin-induced thrombocytopenia provoke direct activation of microvascular endothelial cells

Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis

The era of thromboinflammation: platelets are dynamic sensors and effector cells during infectious diseases

Platelets: active players in the pathogenesis of arthritis and SLE

Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms

COVID-19 patients often show high-titer non-plateletactivating anti-PF4/heparin IgG antibodies

Antigens involved in heparin-induced thrombocytopenia

How to cite this article

Antibody-mediated platelet activation in COVID-19: A coincidence or a new mechanism of the dysregulated coagulation system