Coagulation and fibrinolysis in cancer

Haemostasis is a system of finely adjusted interactions between cells, enzymatic reaction cascades and inhibitors. Disturbances of this balance occur in many disorders, especially in inflammatory processes, septicaemia and cancer. In such cases malignant cells and infectious organisms activate the plasmatic enzyme cascades, especially of the coagulation and fibrinolysis cascades. The resulting consumption and proteolytic degradation of the regulatory proteins contribute to hypercoagulability and secondarily to reactive fibrinolysis, and these may then lead to local thromboses and haemorrhages. These pathogenic events culminate in disseminated intravascular coagulation (DIC), frequently with organ failure and death. Factors of both plasmatic systems are also "misused" by malignant cells for the purposes of growth and metastasis. Prominent examples of this misuse are the formation of a protective fibrin shield against the endogenous defence mechanisms and the local degradation of tissues for tumor proliferation as well as for cell permeation and invasion. In the search for a potential therapy a number of protease inhibitors, predominantly of enzymes of coagulation and fibrinolysis, have been tested in vivo with regard to their efficacy. So far, however, it has not been possible to find a new uniform treatment principle to inhibit the growth and/or metastasis of different types of tumor. The haemorrhagic diathesis and thromboses frequently associated with tumors are generally treated by substitution with plasma components, especially concentrates of coagulation factors and inhibitors.