Venous Thrombosis

Venous thrombosis kills about 300,000 Americans each year and is the leading cause of loss of disability-adjusted life years in hospital patients around the world, making the disease a major public health concern.  Additionally, venous thrombosis can, and often does, lead to further dangerous complications, such as pulmonary embolism and post-thrombotic syndrome.  Venous thrombosis occurs when red blood cell-rich thrombi form in veins due to abnormal interactions between three factors—hypercoagulability, reduced blood flow, and endothelial dysfunction.  We have helped to elucidate specific pathobiological mechanisms contributing to venous thrombosis, including specific roles for fibrinogen, prothrombin, factor VIII, and factor XIII.  We are interested in further discerning mechanisms and potential therapeutic targets to determine new and more effective clinical treatments. 

Interplay among abnormalities in blood components, the vasculature, and blood flow contribute to the development of venous thrombosis. Venous thrombosis involves the formation of fibrin-rich “red clots” that result from exposure of procoagulant activity on intact endothelium plus plasma hypercoagulability, in reduced or static blood flow. Venous thrombi are thought to initiate behind valve pockets, in which reduced or static flow decreases wall shear stress that normally regulates endothelial cell phenotype. TM = thrombomodulin; EPCR = endothelial protein C receptor; II = prothrombin; IIa = thrombin; TF = tissue factor; Fgn = fibrinogen; RBC = red blood cells.

Interplay between abnormalities in blood components, the vasculature, and blood flow contribute to the development of venous thrombosis.  Abbreviations: TM, thrombomodulin; EPCR, endothelial protein C receptor; II, prothrombin; IIa, thrombin; TF, tissue factor; Fgn, fibrinogen; RBC, red blood cells

Wolberg AS, Aleman MM, Leiderman K, Machlus KR. Procoagulant activity in hemostasis and thrombosis: Virchow’s triad revisited. Anesth Analg. 2012;114(2):275-285.