Prevention and management of thrombosis in hospitalised patients with COVID-19 pneumonia

Abstract

A proportion of people infected with SARS-CoV-2 develop moderate or severe COVID-19, with an increased risk of thromboembolic complications. The inflammatory response to SARS-CoV-2 infection can cause an acute-phase response and endothelial dysfunction, which contribute to COVID-19-associated coagulopathy, the clinical and laboratory features of which differ in some respects from those of classic disseminated intravascular coagulation. Understanding of the pathophysiology of thrombosis in COVID-19 is needed to develop approaches to management and prevention, with implications for short-term and long-term health outcomes. Evidence is emerging to support treatment decisions in patients with COVID-19, but many questions remain about the optimum approach to management. In this Viewpoint, we provide a summary of the pathophysiology of thrombosis and associated laboratory and clinical findings, and highlight key considerations in the management of coagulopathy in hospitalised patients with severe COVID-19, including coagulation assessment, identification of thromboembolic complications, and use of antithrombotic prophylaxis and therapeutic anticoagulation. We await the results of trials that are underway to establish the safety and benefits of prolonged thromboprophylaxis after hospital discharge.

Figure

Pathogenetic pathways of coagulopathy in COVID-19 and associated clinical manifestations SARS-CoV-2 elicits a strong inflammatory response orchestrated by various inflammatory mediators, such as interleukin-6 (IL-6), tumour necrosis factor (TNF), C-C motif chemokine 2 (CCL2 or monocyte chemoattractant protein 1 [MCP-1]), and granulocyte-colony stimulating factor (G-CSF), which leads to activation of mononuclear cells. These cells express tissue factor on their surface, leading to thrombin generation and subsequent fibrinogen-to-fibrin conversion. Simultaneously, SARS-CoV-2 can directly infect and damage endothelial cells, causing massive release of endothelial cell constituents, such as plasminogen activators and von Willebrand factor (vWF). Plasminogen activator release can contribute to fibrinolysis, but might also affect tissue remodelling (eg, increasing vascular permeability and contributing to pulmonary oedema) through plasmin-mediated activation of matrix metalloproteinases. Massive release of high-molecular-weight vWF overwhelms a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13, the cleaving protease of vWF multimers), causing even higher levels of ultralarge multimeric forms of this factor, mediating strong platelet–vessel wall interaction. Clinically, thrombin generation, fibrin formation, and fibrinolysis result in a high risk of venous thromboembolism, very high levels of D-dimer (a strong marker for adverse outcomes), and abnormal turnover of fibrin in the lung (a pathological hallmark of acute respiratory distress syndrome). The resulting elevated levels of ultralarge multimeric vWF might cause thrombotic microangiopathy and microvascular platelet thrombi. Adapted from Levi and Thachil, by permission of Georg Thieme Verlag KG.