COVID-19: Thrombosis, thromboinflammation, and anticoagulation considerations

Abstract

Vascular endothelial injury is a hallmark of acute infection at both the microvascular and macrovascular levels. The hallmark of SARS-CoV-2 infection is the current COVID-19 clinical sequelae of the pathophysiologic responses of hypercoagulability and thromboinflammation associated with acute infection. The acute lung injury that initially occurs in COVID-19 results from vascular and endothelial damage from viral injury and pathophysiologic responses that produce the COVID-19-associated coagulopathy. Clinicians should continue to focus on the vascular endothelial injury that occurs and evaluate potential therapeutic interventions that may benefit those with new infections during the current pandemic as they may also be of benefit for future pathogens that generate similar thromboinflammatory responses. The current Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) studies are important projects that will further define our management strategies. At the time of writing this report, two mRNA vaccines are now being distributed and will hopefully have a major impact on slowing the global spread and subsequent thromboinflammatory injury we see clinically in critically ill patients.

Keywords: COVID-19; anticoagulant therapy; coagulopathy; disseminated intravascular coagulation; endothelial cell; thrombosis.

FIGURE 1

Mechanisms of coagulation activation and thromboinflammation in COVID‐19. Both pathogens (viruses) and damage‐associated molecular patterns (DAMPs) from injured host tissue can activate monocytes. Activated monocytes release inflammatory cytokines and chemokines that stimulate neutrophils, lymphocytes, platelets, and vascular endothelial cells. Monocytes and other cells express tissue factor and phosphatidylserine on their surfaces and activate coagulation. Healthy endothelial cells maintain their antithrombogenicity by expressing glycocalyx and its binding protein antithrombin. Damaged endothelial cells change their properties to procoagulant following disruption of the glycocalyx and loss of anticoagulant proteins. From Iba T, Levy JH, et al with permission

FIGURE 2

In the undamaged lung (left), continuous blood flow and effective oxygenation are recognized. COVID‐19 infection causes an intense inflammatory reaction (right). The lung tissue damages are induced by uncontrolled activation of lymphocytes and possibly neutrophil activation (neutrophil extracellular trap [NET] formation). Increased pulmonary production of platelets is also involved in the defense process. In the damaged lung, the virulence of COVID‐19 or unabated inflammatory reaction causes pulmonary microthrombi, endothelial damage, and vascular leakage. The host intends to control the thrombus formation by vigorous fibrinolysis as lung has high fibrinolytic capacity. The fibrin‐degraded fragment (D‐dimer) spills into the blood and is detected in the blood samples. From Iba T, Levy JH et al with permission