Changes of the coagulation and fibrinolysis system in malignancy: Their possible impact on future diagnostic and therapeutic procedures

The interaction between malignant cell growth and the coagulation and fibri nolysis system has been a well known phenomenon for decades. During recent years, this area of research has received new attention. Experimental data suggest a role for the coagulation and fibrinolysis system in tumor develop ment, progression and metastasis. Also, clinical research suggests that tar geting the coagulation system or fibrinolysis system might influence the co urse of malignant disease beneficially. This paper reviews data on various hemostatic and fibrinolytic parameters in malignancy; the possible use of s uch parameters as risk markers in oncology patients; and possible targets o f anti-neoplastic: therapies using anticoagulant and/or antifibrinolytic st rategies. Current evidence suggests that the tissue factor/factor VIIa path way mediates the most abundant procoagulant stimulus in malignancy via the increase in thrombin generation. Tissue factor has been suggested to mediat e pro-metastatic properties via coagulation-dependent and coagulation-indep endent pathways; tissue factor has also been implicated in tumor neo-angiog enesis. However, so far no model has been validated that would allow the us e of tissue factor in its soluble or insoluble form as a marker for risk st ratification in tumor patients. On the other hand, there is now good eviden ce that parts of the fibrinolytic system, such as urokinase-type plasminoge n activator and its receptor ("uPAR"), can be used as strong predictors of outcome in several types of cancer, specifically breast cancer. Observation of various treatment options in patients with thomboembolic disease and ca ncer as well as attempts to use anticoagulants and/or therapies modulating the fibrinolytic system as anti-neoplastic treatment strategies have yielde d exciting results. These data indicate that anticoagulant therapy, and spe cifically low molecular weight heparin therapy, is likely to have anti-neop lastic effects; and that their use in addition to chemotherapy will probabl y improve outcome of tumor treatment in certain types of cancer. However, t he body of clinical data is still relatively small and the question whether or not we should routinely consider the coagulation and/or fibrinolysis sy stem as therapeutic targets in cancer patients is yet to be answered.