Malignant neoplasms change the rheological properties of the blood, leading to a higher risk of thrombosis. Treatment of a cancer also affects the haemostasis. Recent studies carried out in the Deutsches Krebsforschungszentrum (Heidelberg) showed that not only the cancer is causing the thrombosis, but the prothrombotic trend may increase the risk of malignant neoplasm occurrence.

A number of coagulation factors and their cofactors is known. Fibrinogen is extremely important for the haemostasis. It is the main factor affecting the fluidity of blood and it determines the reversible aggregation of erythrocytes, predisposing to thrombosis. Moreover fibrinogen promotes thrombocytes aggregation through binding to the glycoprotein GP IIb/IIIa receptor, which is located on the platelets surface and changes their reactivity by increasing the ADP-mediated degranulation. Increased fibrinogen levels cause an excessive tendency towards platelets aggregation and increase the risk of thrombosis, what means specific clinical states. Fibrinogen binds leukocytes through receptors on their surface and is a ligand for ICAM-1 (Intercellular Adhesion Molecule – 1 ), which is located on the platelets and endothelial cells. Therefore it promotes adhesion of platelets and leukocytes to the endothelial cells, which is associated with inflammation process. Factor V Leiden is a mutation of factor V and causes hypercoagulability of the blood. The most common congenital coagulation abnormality is von Willebrand disease, associated with deficiency of factor of the same name. Von Willebrand factor is a multimeric serum glycoprotein, produced by vessels endothelium, subendothelial connective tissue and by megakaryocytes. It is involved in primary hemostasis as an adhesive protein connecting thrombocytes to the collagen and secondary hemostatis creating a complex with factor VIII, protecting it against proteolysis. It is considered that von Willebrand factor is a marker of endothelial cell dysfunction. Factor XIII is an enzyme catalyzing a reaction involving the stabilization of fibrin.

Scientist from the Deutsches Krebsforschungszentrum in Heidelberg, analyzed polymorphisms, which are genetic changes, of the coagulation factors. They observed six genes, evaluated among 1800 colorectal cancer patients and in the control group of the same size. It appeared that factor V Leiden gene polymorphism was associated with six times more frequent occurrence of colorectal cancer among the polymorphic alleles carriers. The factor XIII gene polymorphism was correlated with 15% lower risk of the colorectal cancer. The other four polymorphisms (among fibrinogen, prothrombin, PAI-1, MTHFR genes) were not associated with occurrence of malignant neoplasm among their polymorphic alleles carriers. An interesting detail is the fact that not every genetic change, which enhances blood coagulation properties automatically increases the risk of developing colorectal cancer. There are also statistical differences between people who are carriers of one variant of the gene, and such with the same variant of the gene present on both chromosomes. It is therefore necessary to continue studies that will scope on these dependencies. Scientists devote themselves to this theme, because there is a possibility that, since increased coagulation properties promote the occurrence of colorectal cancer, it is possible that drugs affecting haemostasis, may inhibit malignant cancer development. Can it be so simple?

Written by: Karolina Kłoda MD, PhD

Source:
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4. http://medtube.pl/angiologia/filmy-medyczne/8917-zakrzep-kaskada-krzepniecia-112-fizjologia-usmle-step-1

Want to know more about colorectal cancer? Watch on medtube.net: Colorectal cancer surgery – 3D Medical Animation