Malignancy as a solid-phase coagulopathy: implications for the etiology, pathogenesis, and treatment of cancer

This overview of the coagulation biology of cancer is intended primarily for those unfamiliar with the link between the coagulation mechanism and neoplasia. Because the literature on this topic is extensive, citations will be primarily of previous reviews that provide detailed references. The clotting mechanism is fundamentally deranged in malignancy and, unlike the physiological hemostatic response to injury, is incapable of self-attenuation. Clotting activation may predict future cancer and the outcome of existing cancer, and participates in tumor growth. Anticoagulant therapy in patients with malignancy achieves more than control of cancer-related thrombosis. Modification of coagulation reactions relevant to particular tumor types improves the course of the disease. Viewing malignancy as a solid-phase coagulopathy provides insights into possible "upstream" causes of malignant transformation and explanations for the aberrant behavior of transformed cells and suggests innovative experimental interventions. Coagulation biology has broadened and deepened our understanding of neoplasia, and suggested testable strategies for the prevention and treatment of cancer. However, relationships between clotting and cancer progression have been established primarily from model systems. Although limited experience to date in human disease has supported these concepts, resolution of cause-and-effect relationships will require performance of additional rationally designed clinical trials.