Basic mechanisms and pathogenesis of venous thrombosis.
In 1856 Virchow proposed a triad of causes for venous thrombosis, postulating that stasis, changes in the vessel wall or changes in the blood could lead to thrombosis. We now know that abnormally high levels of some coagulation factors and defects in the natural anticoagulants contribute to thrombotic risk. Among these, factor V Leiden, which renders factor Va resistant to activated protein C, is the most prevalent with approximately 5% of the Caucasian population having this genetic alteration. These genetically controlled variants in coagulation factors work in concert with other risk factors, such as oral contraceptive use, to dramatically increase thrombotic risk. While these abnormalities in the blood coagulation proteins are associated with thrombotic disease propensity, they are less frequent contributors to thrombosis than age or cancer. Cancer increases thrombotic risk by producing tissue factor to initiate coagulation, by shedding procoagulant lipid microparticles or by impairing blood flow. Age is the strongest risk factor for thrombosis. Among possible reasons are fragility of the vessels potentially contributing to stasis, increased coagulation factor levels, impaired function of the venous valves, decreases in the efficacy of natural anticoagulants associated with the vessel wall, increased risk of immobilization and increased risk of severe infection.
Esmon
Charles T
CT
Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, and Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. charles-esmon@omrf.org
D000375:Aging / Q000097:blood / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology*; D005165:Factor V / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000378:metabolism; D011486:Protein C / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D020246:Venous Thrombosis / Q000097:blood* / Q000209:etiology* / Q000378:metabolism
D011486:Protein C; C095381:factor V Leiden; D005165:Factor V; D013925:Thromboplastin
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