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THROMBOPHILIA

COVID-19-Associated Coagulopathy June 2020

Critically ill patients with COVID-19 have significant coagulation abnormalities which can result in venous thromboembolism, ischemic stroke, myocardial infarction, and arterial thrombosis and embolism. Institutional  and society guidelines for prophylactic and therapeutic anticoagulation are evolving rapidly and require close attention by  emergency physicians.

INTRODUCTION

Most patients develop arterial or venous thromboses because of local factors (e.g., a focal atherosclerotic lesion producing a thrombus in a coronary artery) or major systemic events (e.g., trauma, surgery, or prolonged immobilization). However, several inherited genetic mutations and acquired conditions predispose patients to venous thromboembolism with some studies finding up to 50% of patients with unprovoked venous thromboembolism having a hypercoagulable disorder or thrombophilia (Table 234-1).1 No specific risk factor or condition guarantees abnormal thrombosis. Rather, similar to seizures, patients have a varying threshold for clotting. Risks for clotting from genetic, acquired, and environmental factors are additive and, in some cases, multiplicative.2

TABLE 234-1Hypercoagulable States

PATHOPHYSIOLOGY

Several physiologic systems ensure that blood clots do not extend beyond the necessary area. The two most clinically important pathways involve antithrombin and protein C (Table 234-2). Antithrombin (also called antithrombin III) is a plasma-based protein that inhibits several activated coagulation factors, primarily thrombin, factor Xa, and factor IXa. Both unfractionated heparin and low-molecular-weight heparin possess anticoagulant activity by increasing the rate by which antithrombin inhibits these factors: approximately 2000- to 4000-fold for thrombin, about 500- to 1000-fold for factor Xa, and about a million-fold for factor IXa. Protein C is a vitamin K–dependent plasma protein that binds to the endothelial cell surface and is activated by thrombin. Activated protein C cleaves both factor Va and factor VIIIa, inhibiting both the common pathway and the intrinsic pathway. Protein S, another vitamin K–dependent plasma protein, is a cofactor that increases the inhibitory action of activated protein C by about 20-fold.

TABLE 234-2Functions of Coagulation Proteins in Protein C and Antithrombin Systems

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