Hemostatic disorders are associated with the course and outcomes of COVID-19

Background : Thrombotic events are common in COVID-19 but little understood. Aims : To reveal if coagulopathies relate to the course and outcomes of COVID-19. Methods : We examined 235 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Informed consent was obtained and the study was approved by the Ethics Committee of K(V)FU. Hemostasis was assessed using a thrombodynamics assay, thromboelastography, fibrinogen and Ddimer levels, prothrombin time, and soluble fibrin complexes (ethanol gelation test). Blood clot contraction (retraction) kinetics was performed along with electron microscopy of platelets and clots and platelet flow cytometry. The hemostatic parameters were correlated with biochemical and hematological tests. Results : Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about 1/4 cases were associated with a high level of C-reactive protein, which may impede coagulation in vitro and mask the inflammatory thrombophilia in vivo . Contraction of blood clots was hindered and incomplete in about 1/2 patients, especially in severe and fatal cases. Suppression of clot contraction correlated directly with prothrombotic parameters, including a high D-dimer level. A decrease in the platelet contractility was mainly due to moderate thrombocytopenia in combination with chronic platelet activation and secondary platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompact intravital clots are more obstructive but could also be prone to bleeding. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. Conclusions : The results obtained i) confirm the importance of hemostatic disorders in COVID-19;ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction;iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.