Abstract Number: PB/CO06
Meeting: ISTH 2020 Congress
Background: Patients with severe COVID-19 pneumonia experience hypoxemia, endothelial dysfunction and a systemic cytokine storm, leading to micro- and macro-thrombosis. The cytokine storm may lead to consistent blood cell activation, resulting in a generalized cell-based Tissue Factor (TF)-mediated activation of blood coagulation, release of procoagulant microvesicles (MVs), and in a massive platelet activation.
Aims: To assess in 46 COVID-19 patients: 1) levels of TF+ circulating cells and MVs; 2) residual plasma thrombin generation capacity despite heparin treatment; and 3) extent of platelet and endothelial activation. Finally, through an in vitro approach, we verified whether: 4) plasma from COVID-19 patients was able to reproduce the platelet activation observed in vivo when added to blood cells from healthy subjects (HS); 5) treatment with tocilizumab or antiplatelet drugs was effective in reverting platelet activation.
Methods: TF+ platelets, monocytes, granulocytes, and platelet-leukocyte aggregates (PLA), platelet activation markers (P-selectin and the percentage of PLA) and the MVs were evaluated by whole-blood-flow cytometry. Thrombin generation (TG) was assessed by CAT. L-arginine (Arg)/nitric oxide (NO) biosynthetic pathway was also assessed. The extent of activation was compared to that of HS.
Results: In COVID-19 patients TF+ cells and MVs were two- to four-fold higher than HS (p< 0.0001). P-selectin and PLA behaved similarly. A residual TG correlated with disease severity. Global Arg bioavailability ratio was significantly reduced in COVID patient (p< 0.0001). COVID plasma, when added to blood cells of healthy subjects, closely reproduced the activation observed in vivo in terms of TF induction and platelet stimulation. This effect was blunted by preincubation with tocilizumab as well as by aspirin and AR-C69931MX.
Conclusions: All toghether these results provide insights into the IL-6 driven pathophysiological mechanisms that trigger the hypercoagulable state in COVID-19 and suggest the potential effectiveness of antiplatelet drugs.
To cite this abstract in AMA style:Canzano P, Brambilla M, Tortorici E, Cosentino N, Porro B, Pengo M, Bonomi A, Veglia F, Parati G, Cavalca V, Omodeosalè E, Tremoli E, Camera M. Disantangling the Mechanisms behind the Thrombotic Complications of COVID-19 Patients: Insights into Platelet and Endothelial Activation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/disantangling-the-mechanisms-behind-the-thrombotic-complications-of-covid-19-patients-insights-into-platelet-and-endothelial-activation/. Accessed January 26, 2022.
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