Review: Viral infections and mechanisms of thrombosis and bleeding

Abstract

Viral infections are associated with coagulation disorders. All aspects of the coagulation cascade, primary hemostasis, coagulation, and fibrinolysis, can be affected. As a consequence, thrombosis and disseminated intravascular coagulation, hemorrhage, or both, may occur. Investigation of coagulation disorders as a consequence of different viral infections have not been performed uniformly. Common pathways are therefore not fully elucidated. In many severe viral infections there is no treatment other than supportive measures. A better understanding of the pathophysiology behind the association of viral infections and coagulation disorders is crucial for developing therapeutic strategies. This is of special importance in case of severe complications, such as those seen in hemorrhagic viral infections, the incidence of which is increasing worldwide. To date, only a few promising targets have been discovered, meaning the implementation in a clinical context is still hampered. This review discusses non-hemorrhagic and hemorrhagic viruses for which sufficient data on the association with hemostasis and related clinical features is available. This will enable clinicians to interpret research data and place them into a perspective.

Figure 1

Simplified model of the coagulation cascade. Coagulation proteins are given in roman numerals. Products of coagulation activation that can be measured in blood samples are shown in squares: F1 + 2, prothrombin fragment 1 + 2; D‐dimer, fibrin degradation product; TAT, thrombin–antithrombin complex. Natural inhibitors of coagulation shown: TFPI, tissue factor pathway inhibitor; AT, antithrombin; APC, activated protein C (which cleaves activated factors V and VIII). TAFI, thrombin‐activatable fibrinolysis inhibitor. t‐PA, tissue plasminogen activator; PAI‐1, plasminogen activator inhibitor‐1. Adapted from [van Gorp et al., 1999].