Hemostasis and Malignancy

Abstract

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

“…The evidence linking hemostasis and malignancy has been derived from numerous clinical, laboratory, pharmacological, and histologic studies [22]. These studies have provided data on the high frequency of clinical and subclinical thrombotic complications and the myriad of clotting defects in cancer patients.…”

Coagulation and cancer: Implications for diagnosis and management

“…TF has been found in promyelocytic leukemia 40 and solid tumors, such as gastric and colorectal cancer 90 and it seems to be also involved in several stages of metastatic development, especially in the neovascularization process which supports hematogenous tumor dissemination. 31 CP is a cysteine proteinase that directly activates factor X, independently from factor VII; it is found principally in malignant tissues, but also in human fetal tissue. 23 Other PCAs have been demonstrated in human tumors, including a factor XIII-like activity capable of fibrin covalent crosslinking and a factor V receptor associated with tumor cell plasma membrane that facilitates the assembly of the protrombinase complex.…”

“…Esophagogastric varices with subsequent bleeding may be the first symptom of this disease; and ascites is present only in acute cases. 31 Microvascular arterial thrombosis of the extremities and central nervous system are characteristic complications of myeloproliferative diseases, in particular essential thrombocythemia and polycythemia vera. Digital ischemia may present initially as an excruciating pain in the feet, in the absence of physical signs; progression of arterial occlusion leads to pregangrenous and eventually gangrenous changes in the digits (digital ischemia has also been reported as a paraneoplastic manifestation of several types of cancer).…”

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

“…Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumour fibrin deposition appear to be important causative agents. 101 Tissue factor is involved in angiogenesis 102 (see below), cell migration, 103 and tumour cell invasion. 104 More recently, it was demonstrated in human prostate cancer cells that tissue factor binds plasminogen with high affinity through an interaction between kringles 1-3 of plasminogen and the extracellular domain of tissue factor.…”