Longitudinal multiparametric characterization of platelet dysfunction in COVID-19: Effects of disease severity, anticoagulation therapy and inflammatory status

Abstract

Introduction Defects of platelet functional responses in COVID-19 were reported, but their origin and pathophysiological significance are unclear. The objective of this study was to characterize the thrombocytopathy in COVID-19. Materials and methods Analysis of platelet functional responses to activation by flow cytometry and aggregometry in 46 patients with confirmed COVID-19 of different severity (non-ICU, ICU, and ECMO) over the course of hospitalization alongside with plasma coagulation, inflammatory markers (CRP, fibrinogen, NETosis assays in smears) was performed. Results and conclusions All patients had increased baseline percentage of procoagulant platelets (healthy: 0.9 ± 0.5%; COVID-19: 1.7 ± 0.6%). Patients had decreased agonist-induced platelet GPIb shedding (1.8 ± 0.7 vs 1.25 ± 0.4), P-Selectin exposure (1.51 ± 0.21 vs 1.1 ± 0.3) and aggregation. The values of these parameters among the non-ICU and ICU cohorts differed modestly, while the ECMO cohort differed significantly. Only ECMO patients had pronounced thrombocytopenia. While inflammatory markers improved over time, the observed platelet functional responses changed only moderately. SARS-CoV-2 RNA was found in 8% of blood samples and it did not correlate with platelet counts or responses. All patients had increased NETosis that moderately correlated with platelet dysfunction. High cumulative dosages of LMWH (average > 12,000 IU/day over 5 days) resulted in an improvement in platelet parameters. The observed pattern of platelet refractoriness was reproduced by in vitro pre-treatment of washed platelets with subnanomolar thrombin or perfusion of blood through a collagen-covered flow chamber. We conclude that platelet dysfunction in COVID-19 is consistent with the intravascular-coagulation-induced refractoriness rather than with an inflammation-induced mechanism or a direct activation by the virus.

Post-COVID Syndrome in Adults—An Overview

“…However, in recent studies, platelets from COVID-19 patients were shown to exhibit impaired aggregation and impaired activation of the responsible integrin receptor αIIbβ3 (GPIIb-IIIa) upon agonist-induced stimulation in vitro [ 56 , 57 ]. The reduced responsiveness of platelet functions ex vivo was not due to prior platelet activation in vivo.…”

Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation

“…Platelet–leukocyte complexes were elevated in COVID-19 patients, with even higher numbers observed in ICU patients [ 155 ]. Platelets were pre-activated: changes in P-selectin exposure and GPIb shedding and elevated sizes and higher levels of sCD40L and sP-selectin were shown [ 156 , 157 , 158 ]. A recent review of COVID-19-associated thrombosis, focusing on all potential contributors, including platelets and neutrophils, was published [ 159 ].…”

Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon

“…CD61 expression in the quiescent state ( supplemental Figure 3 C) was normal for all patients. Patients with KHE/KMP without HR had increased CD62p binding in the resting state, but these differences were not statistically significant ( supplemental Figure 3 D).In combination with the increased amounts of PS-positive platelets ( supplemental Figure 3 E), these results could be interpreted so that platelets are preactivated, 48 probably because of their contact with the tumor and consumption by it, and this resulted in decreased platelet counts and platelet age. 49 …”