Antibody-induced procoagulant platelets in severe COVID-19 infection.

Abstract

The pathophysiology of COVID-19-associated thrombosis seems to be multifactorial. We hypothesized that COVID-19 is accompanied by procoagulant platelets with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization. Platelets from COVID-19 patients in the intensive care unit (ICU; n = 21) showed higher ΔΨm depolarization, cytosolic Ca2+, and PS externalization compared with healthy controls (n = 18) and non-ICU COVID-19 patients (n = 4). Moreover, significant higher cytosolic Ca2+ and PS were observed compared with a septic ICU control group (ICU control; n = 5). In the ICU control group, cytosolic Ca2+ and PS externalization were comparable with healthy controls, with an increase in ΔΨm depolarization. Sera from COVID-19 patients in the ICU induced a significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+, and PS externalization) compared with healthy volunteers and septic ICU controls. Interestingly, immunoglobulin G fractions from COVID-19 patients induced an Fcγ receptor IIA-dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+, and PS externalization). Enhanced PS externalization in platelets from COVID-19 patients in the ICU was associated with increased sequential organ failure assessment score (r = 0.5635) and D-dimer (r = 0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared with those without. The strong correlations between markers for apoptosic and procoagulant platelets and D-dimer levels, as well as the incidence of thrombosis, may indicate that antibody-mediated procoagulant platelets potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.

• Authors: Karina Althaus, Irene Marini, Jan Zlamal, Lisann Pelzl, Anurag Singh, Helene Häberle, Martin Mehrländer, Stefanie Hammer, Harald Schulze, Michael Bitzer, Nisar Malek, Dominik Rath, Hans Bösmüller, Bernard Nieswandt, Meinrad Gawaz, Tamam Bakchoul, Peter Rosenberger
• Journal: Blood (Blood) Vol. 137 Issue 8 Pg. 1061-1071 (02 25 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 33512415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Immunoglobulin G
• Phosphatidylserines
• Calcium

Topics

• Adult
• Aged
• Apoptosis
• Blood Coagulation
• Blood Platelets (metabolism, pathology)
• COVID-19 (blood, complications, metabolism, pathology)
• Calcium (metabolism)
• Cohort Studies
• Female
• Humans
• Immunoglobulin G (metabolism)
• Male
• Membrane Potential, Mitochondrial
• Middle Aged
• Phosphatidylserines (metabolism)
• SARS-CoV-2 (isolation & purification, physiology)
• Thrombosis (blood, etiology, metabolism, pathology)