Thrombosis and Cancer

Abnormal hemostasis is a fundamental property of malignant disease, not merely an epiphenomenon attributable to therapy or to chronic illness. Many types of tumor cells express clotting initiators such as tissue factor and act again late in the coagulation pathway by providing a surface for prothrombinase generation. Thus, entry of tumor cells into the plasma, as during metastasis, may be expected to trigger intravascular clotting. However, and perhaps of greater importance, solid tumors growing outside of the blood vasculature regularly deposit fibrin locally in the tissues. They do so by rendering the microvasculature hyperpermeable, allowing fibrinogen and other plasma-clotting proteins to leak into the extravascular space where procoagulants associated with tumor cells or with benign stromal cells initiate clotting. Both fibrin deposition and turnover in solid tumors proceed at rapid rates. Thus, whether attributable to events in the intra- or extra-vascular space, the result is the same: abnormal clotting and fibrinolysis whose consequences may include protection from host inflammatory cells, modulation of the immune response, and induction of angiogenesis.