Review: Laboratory markers quantifying prothrombin activation and actions of thrombin in venous and arterial thrombosis do not accurately assess disease severity or the effectiveness of treatment

Abstract

SummaryThrombin is normally produced for hemostasis and physiological wound healing. Increased thrombin production in vivo, cell activation and inflammation mediated in part by thrombin are hallmarks of both arterial and venous thrombosis. Thrombin generates (pro) coagulant, mitogenic, inflammatory and anticoagulant responses by interacting witha variety of cells in vivo.Both direct and indirect thrombin inhibitors are effective drugs for preventing and treating the consequences of arterial and venous thrombosis. For these reasons, measurements of the production and activities of thrombin in vivo have the potential for gauging the extent of thromboembolism and the responses of patients to anticoagulant, antiplatelet and anti-inflammatory drugs. How-ever, a critical review of published information suggests that measurement of thrombin production and activity in patients at risk for and in patients with significant thrombosis generally does not provide information useful for clinical decision-making. This lack of clinical utility of levels of thrombin production in vivo may arise from two causes: the inability of the measurement to differentiate between physiological (hemostatic) and disease-related (pathological) sources and/or causes of thrombin production in vivo, and the inability of antithrombotic treatment modalities to permanently eliminate the stimuli that cause increased thrombin production evident in venous and arterial thrombosis.