Recent Pathophysiological Insights Are Advancing the Treatment of Venous Thromboembolism

Venous thromboembolism, defined as deep vein thrombosis and pulmonary embolism, is the third leading cause of cardiovascular deaths globally. Long-term complications of unresolved venous thrombi include post-thrombotic syndrome in the legs and chronic thromboembolic pulmonary hypertension. As the venous thrombus ages, the acute, fibrin, and red blood cell-rich composition changes to a chronic cellular, fibrotic mass that does not respond to presently available therapeutic approaches. Standard anticoagulation treatment does not fully prevent recurrent thrombosis and may cause serious bleeding. Thrombolytic therapy may resolve thrombi but it has unacceptable bleeding risks. Recent drug discovery for acute venous thromboembolism has focused on novel targets that may provide enhanced safety and efficacy. Additional therapeutic strategies have focused on the transition phase of acute-to-chronic venous thromboembolism with anti-inflammatory agents, statins, and vasodilator drugs. In this review, we discuss the mechanisms of venous thrombus aging, its clinical implications, and the latest developments in pharmacotherapeutic approaches for venous thromboembolism.