P-Selectin Inhibition Therapeutically Promotes Thrombus Resolution and Prevents Vein Wall Fibrosis Better Than Enoxaparin and an Inhibitor to von Willebrand Factor

摘要

Deep vein thrombosis (VT) and pulmonary embolism, known collectively as venous thromboembolism, affect an estimated 900000 people in the United States each year, resulting in ?300000 deaths.1 Most of those deaths occurred within 1 month of the initial diagnosis.2 Anticoagulation is the current standard treatment for the prevention of VT, VT recurrence, pulmonary embolism, and the progression of the thrombus. However, it does not lyse the thrombus or prevent the development of post-thrombotic syndrome. In addition, it carries with it significant bleeding risks, such as intracra-nial hemorrhage, which occurs in 1.15% patients per year with a case fatality rate (major bleeding) of 13%.3 Thus, new treatment options that limit bleeding risk, while decreasing thrombotic risk, should be investigated. Recently, it has been demonstrated that P-selectin and von Willebrand factor (vWF) can mediate events associated with VT.4"7 Both proteins are stored by platelets and endothelial cells (P-selectin is a component of the membrane and also the matrix of the a granule and the Weibel-Palade bodies), can be released from platelets and endothelial cells by prothrombotic and inflammatory factors generated on cell activation, and can be localized to the surface of the cells. The surface that expresses P-selectin and vWF can promote accumulation of plasma-derived, cell-associated procoagulant factors and cells (platelets and leukocytes) that will promote vein wall injury and thrombus formation.