Addressing the Issue of the Pathogenesis of Deep Vein Thrombosis In Cancer

Abstract 4220

The risk of thrombotic complications during tumor development has been the focus of several clinical studies over the past decades. Thrombotic disease is a common cause of death in cancer patients and almost one in five of all symptomatic cases of Deep Vein Thrombosis (DVT) are thought to be cancer related. Tumor cells generate and profit from a local and systemic hypercoagulable state, which promotes tumor growth, angiogenesis, and metastasis. The resulting procoagulant state is responsible for the heightened risk for thrombotic complications and the etiology of the resulting DVT event. However, despite the fact that some molecules, such as tissue factor, have recently been described as potential modulators of clot formation in DVT, the true trigger of DVT in cancer patients remains unknown. To determine whether the presence of cancer cells can trigger formation of a thrombus in a deep vein in vivo, we combined a murine model of Trousseau's Syndrome with a model of DVT. First, we induced the development of a tumor by subcutaneous injection of syngeneic pancreatic tumor cells in C57BL/6 mice. It was previously demonstrated that these mice have significantly reduced tail bleeding time and time to occlusion in injured mesenteric arteries and veins compared to control vessels. After 3 hours of partial flow restriction of the inferior vena cava, we observed that all tumor-bearing mice developed an occlusive thrombus (n=8) while only 29% of the control mice (n=7) formed occlusive thrombi. Interestingly, perfusion of cancer-derived microparticles in mice also induced thrombus formation in this DVT model, reproducing the tumor-bearing mice phenotype. This new approach showed that microparticles shed by cancer cells have a key role in the pathogenesis of cancer-associated DVT, and they may become a reasonable pharmaceutical target to prevent thrombosis associated with cancer development.