The prothrombotic state in cancer: pathogenic mechanisms

Abstract

Thrombosis and disseminated intravascular coagulation (DIC) are common complications in cancer. Patients with malignancy have a prothrombotic state due to the ability of almost all type of cancer cells to activate the coagulation system. However, none of the haemostatic markers of coagulation has any predictive value for the occurrence of the thrombotic events in one individual patient. The pathogenesis of the prothrombotic state in cancer is complex and, probably, multifactorial. Prothrombotic factors in malignancy include the tumour production of procoagulants (i.e., tissue factor (TF) and cancer procoagulant (CP)) and inflammatory cytokines, and the interaction between tumour cells and blood (i.e., monocytes/macrophages, platelets) and endothelial cells. Other mechanisms of thrombus promotion include some general responses of the host to the tumour (i.e., acute phase, inflammation, angiogenesis), decreased levels of inhibitors of coagulation, and impaired fibrinolysis. In addition, the prothrombotic tendency of cancer patients is enhanced by anticancer therapy, such as surgery, chemotherapy, hormone therapy and radiotherapy, by indwelling central venous catheter, and by haemodinamic compromise (i.e., stasis). However, not all of the mechanisms allowing the prothrombotic state of cancer are entirely understood. Therefore, it is presently difficult to rank the relative weight of these multiple interactions on the basis of the well-recognised clinical evidences of enhanced thrombotic episodes in patients with cancer. In this review we attempt to describe the current proposed mechanisms for the pathogenesis of the prothrombotic state in cancer patient. A better understanding of these mechanisms could help clinicians in the developments of more targeted treatment to prevent thromboembolic complications in cancer patient.