Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients

Canzano, Paola; Brambilla, Marta; Porro, Benedetta; Cosentino, Nicola; Tortorici, Elena; Vicini, Stefano; Poggio, Paolo; Cascella, Andrea; Pengo, Martino F.; Veglia, Fabrizio; Fiorelli, Susanna; Bonomi, Alice; Cavalca, Viviana; Trabattoni, Daniela; Andreini, Daniele; Omodeo Salè, Emanuela; Parati, Gianfranco; Tremoli, Elena; Camera, Marina

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 P2Y(12) inhibitor.