Platelets and Antiplatelet Medication in COVID-19-Related Thrombotic Complications.

Waltraud C Schrottmaier ,Mario Karolyi,Hubert Hackl,David Pereyra,Erich Pawelka,Christian Schörgenhofer,Stefan Heber,Alice Assinger,Matthew Pugh,Justin Oosterlee,Kerstin Kammerer,Jonas Santol,Alexander Zoufaly,Tamara Seitz,Anita Pirabe,Bernd Jilma,Laura Brunnthaler,Anna Schmuckenschlager,Julie Rayes,Marianna Traugott ,Abdullah O Khan ,Sonja M Treiber

doi:10.3389/fcvm.2021.802566

Abstract

Coronavirus disease 2019 (COVID-19) induces a hypercoagulatory state that frequently leads to thromboembolic complications. Whereas anticoagulation is associated with reduced mortality, the role of antiplatelet therapy in COVID-19 is less clear. We retrospectively analyzed the effect of anticoagulation and antiplatelet therapy in 578 hospitalized patients with COVID-19 and prospectively monitored 110 patients for circulating microthrombi and plasma markers of coagulation in the first week of admission. Moreover, we determined platelet shape change and also thrombi in postmortem lung biopsies in a subset of patients with COVID-19. We observed no association of antiplatelet therapy with COVID-19 survival. Adverse outcome in COVID-19 was associated with increased activation of the coagulation cascade, whereas circulating microthrombi did not increase in aggravated disease. This was in line with analysis of postmortem lung biopsies of patients with COVID-19, which revealed generally fibrin(ogen)-rich and platelet-low thrombi. Platelet spreading was normal in severe COVID-19 cases; however, plasma from patients with COVID-19 mediated an outcome-dependent inhibitory effect on naïve platelets. Antiplatelet medication disproportionally exacerbated this platelet impairment in plasma of patients with fatal outcome. Taken together, this study shows that unfavorable outcome in COVID-19 is associated with a profound dysregulation of the coagulation system, whereas the contribution of platelets to thrombotic complications is less clear. Adverse outcome may be associated with impaired platelet function or platelet exhaustion. In line, antiplatelet therapy was not associated with beneficial outcome.

Highlights

Coronavirus disease 2019 (COVID-19) induced by infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a complex syndrome primarily afflicting the airways to cause acute respiratory distress, and causing systemic malfunction of various physiologic systems such as hemostasis [1, 2]
We retrospectively analyzed the impact of antiplatelet therapy on the survival of hospitalized patients with COVID-19 and prospectively monitored plasma markers, circulating microthrombi, and platelet spreading to determine potential effects of platelet dysregulation on hemostatic complications and patient outcome
We found that anticoagulation but not antiplatelet therapy was associated with ameliorated survival in COVID-19 and that complicated disease was associated with enhanced endothelial activation and coagulation dysregulation, whereas platelet-derived microthrombi did not increase in patients with adverse outcome

Summary

Introduction

Coronavirus disease 2019 (COVID-19) induced by infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a complex syndrome primarily afflicting the airways to cause acute respiratory distress, and causing systemic malfunction of various physiologic systems such as hemostasis [1, 2]. Thromboembolic complications are common with early studies reporting overall incidences among hospitalized patients with COVID-19 ranging from 7–46%, with higher rates in critically ill patients requiring intensive care unit (ICU) treatment [3,4,5,6,7]. 0.9–5.6% of hospitalized patients with COVID-19 experience a major or clinically relevant non-major bleeding event, with rates again being higher among the severely ill [7,8,9]. The majority of thrombotic events are venous thromboembolisms, especially symptomatic pulmonary embolisms and deep vein thrombosis, though thrombosis may occur at arterial sites [5, 10,11,12], pointing toward a complex derangement of the hemostatic system that involves both platelet function (primary hemostasis) and the coagulation cascade (secondary hemostasis). Immunothrombosis represents a crucial link among systemic hypercoagulability, endothelial dysfunction, and respiratory failure, where neutrophils, immunogenic platelets, and a dysregulated coagulation cascade work as partners in crime leading to immunothrombotic tissue injury in COVID-19 [15,16,17]

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