The clinical link between cancer and thrombosis has been recognized by Armand Trousseau in 1865. It has now become clear that clotting activation in malignancy not only plays an important role in the evolution of venous thromboembolism (VTE) or systemic coagulation disorders such as disseminated intravascular coagulation, but that multiple components of the haemostatic and fibrinolytic systems are directly involved in tumour progression. In particular, tissue factor (TF) appears to be involved in several pathways relevant to cancer growth and metastasis. Increasing evidence emerges that haemostatic perturbances in cancer patients are, at least in part, controlled by defined genetic events in molecular tumourigenesis including activating and inactivating mutations of oncogenes and tumour suppressor genes, respectively. Long-term therapy with low-molecular-weight heparin (LMWH) is considered as standard treatment for cancer-associated VTE. However, several experimental studies and clinical trials suggest that LMWH may also be beneficial as an adjunct in the treatment of patients with malignant disease. This article provides an overview on the significance, pathogenesis and treatment of cancer-related clotting disorders as well as on the cellular and molecular mechanisms, by which haemostatic components such as TF, platelets and fibrin(ogen) drive tumour progression.
The clinical link between cancer and thrombosis has been recognized by Armand Trousseau in 1865. It has now become clear that clotting activation in malignancy not only plays an important role in the evolution of venous thromboembolism (VTE) or systemic coagulation disorders such as disseminated intravascular coagulation, but that multiple components of the haemostatic and fibrinolytic systems are directly involved in tumour progression. In particular, tissue factor (TF) appears to be involved in several pathways relevant to cancer growth and metastasis. Increasing evidence emerges that haemostatic perturbances in cancer patients are, at least in part, controlled by defined genetic events in molecular tumourigenesis including activating and inactivating mutations of oncogenes and tumour suppressor genes, respectively. Long-term therapy with low-molecular-weight heparin (LMWH) is considered as standard treatment for cancer-associated VTE. However, several experimental studies and clinical trials suggest that LMWH may also be beneficial as an adjunct in the treatment of patients with malignant disease. This article provides an overview on the significance, pathogenesis and treatment of cancer-related clotting disorders as well as on the cellular and molecular mechanisms, by which haemostatic components such as TF, platelets and fibrin(ogen) drive tumour progression.