The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet-leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.
Keywords: ADP, adenosine diphosphate; CAD, coronary artery disease; COVID-19; COVID-19, coronavirus disease-2019; CRP, C-reactive protein; GPA, granulocyte–platelet aggregates; HS, healthy subject; IL, interleukin; IL-6; IL-6R, interleukin-6 receptor; LMWH, low-molecular-weight heparin; MPA, monocyte–platelet aggregates; MV, microvesicle; NO, nitric oxide; NOS, nitric oxide synthase; PGI2, prostacyclin; PLA, platelet–leukocyte aggregates; PS, phosphatidylserine; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; TF, tissue factor; antiplatelet drugs; circulating microvesicles; platelet activation; tissue factor.
© 2021 The Authors.