title: Basic mechanisms and pathogenesis of venous thrombosis.
abstract: 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.
authors.affiliation: 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
authors.forename: Charles T
authors.initials: CT
authors.lastname: Esmon
mesh_terms: 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
chemical_list: D011486:Protein C; C095381:factor V Leiden; D005165:Factor V; D013925:Thromboplastin
references.citation: Br J Haematol. 1988 Aug;69(4):491-7
references.pmid: 3136794
references.citation: J Rheumatol. 2000 Feb;27(2):384-90
references.pmid: 10685802
references.citation: J Vasc Surg. 2005 Aug;42(2):329-36
references.pmid: 16102635
references.citation: Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):395-400
references.pmid: 15692250
references.citation: J Thromb Haemost. 2007 Jul;5 Suppl 1:283-91
references.pmid: 17635738
references.citation: Blood. 1998 Mar 15;91(6):1999-2004
references.pmid: 9490682
references.citation: J Am Geriatr Soc. 2008 Mar;56(3):517-22
references.pmid: 18179500
references.citation: Biochem Biophys Res Commun. 1997 Sep 18;238(2):305-12
references.pmid: 9299500
references.citation: Blood. 2000 Jan 15;95(2):569-76
references.pmid: 10627464
references.citation: Blood. 1984 Dec;64(6):1297-300
references.pmid: 6238642
references.citation: J Exp Med. 2003 Jun 2;197(11):1585-98
references.pmid: 12782720
references.citation: Hematology Am Soc Hematol Educ Program. 2004;:439-56
references.pmid: 15561697
references.citation: Am Heart J. 1996 Oct;132(4):850-5
references.pmid: 8831376
references.citation: Thromb Haemost. 1996 Dec;76(6):824-34
references.pmid: 8971998
references.citation: N Engl J Med. 2001 Aug 9;345(6):408-16
references.pmid: 11496851
references.citation: J Vasc Surg. 2003 Nov;38(5):1075-89
references.pmid: 14603220
references.citation: J Biol Chem. 1989 Mar 25;264(9):4743-6
references.pmid: 2538457
references.citation: Blood. 2005 Jan 1;105(1):192-8
references.pmid: 15339841
references.citation: J Autoimmun. 2000 Sep;15(2):221-5
references.pmid: 10968914
references.citation: Biochem Biophys Res Commun. 1989 Sep 29;163(3):1404-11
references.pmid: 2675842
references.citation: Surg Gynecol Obstet. 1954 Jan;98(1):96-102
references.pmid: 13122392
references.citation: J Exp Med. 2002 Jan 21;195(2):211-20
references.pmid: 11805148
references.citation: J Clin Invest. 1990 Apr;85(4):1090-8
references.pmid: 2156893
references.citation: J Biol Chem. 1992 Oct 5;267(28):20435-43
references.pmid: 1400362
references.citation: J Thromb Haemost. 2005 Aug;3(8):1854-60
references.pmid: 16102052
references.citation: Thromb Haemost. 2001 Oct;86(4):945-8
references.pmid: 11686350
references.citation: Blood. 1989 Feb 15;73(3):712-7
references.pmid: 2521802
references.citation: Lancet. 1999 Apr 3;353(9159):1167-73
references.pmid: 10209995
references.citation: Semin Thromb Hemost. 2006 Apr;32 Suppl 1:49-60
references.pmid: 16673266
references.citation: Proc Natl Acad Sci U S A. 1981 Apr;78(4):2249-52
references.pmid: 7017729
references.citation: Blood. 2009 Aug 6;114(6):1276-9
references.pmid: 19436051
references.citation: Oncologist. 2003;8(4):381-8
references.pmid: 12897335
references.citation: Ann Surg. 1960 Oct;152:678-85
references.pmid: 13774059
references.citation: Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2029-35
references.pmid: 10479642
references.citation: J Clin Invest. 1995 Jan;95(1):309-16
references.pmid: 7814631
references.citation: Blood. 1999 Dec 1;94(11):3839-46
references.pmid: 10572099
references.citation: Angiology. 1969 Mar;20(3):155-76
references.pmid: 5773967
references.citation: Br J Haematol. 1997 Jun;97(4):775-84
references.pmid: 9217176
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2311-5
references.pmid: 10051638
references.citation: Am J Med. 2002 Dec 1;113(8):636-42
references.pmid: 12505113
references.citation: Lancet. 2006 Apr 1;367(9516):1075-1079
references.pmid: 16581406
references.citation: Science. 1981 May 22;212(4497):923-4
references.pmid: 7195067
references.citation: J Vasc Surg. 2000 Feb;31(2):309-24
references.pmid: 10664500
references.citation: Blood. 2000 Mar 1;95(5):1517-32
references.pmid: 10688804
references.citation: Am J Pathol. 1989 May;134(5):1087-97
references.pmid: 2719077
references.citation: Am J Pathol. 2001 Sep;159(3):797-802
references.pmid: 11549570
references.citation: Arch Intern Med. 2005 Jul 11;165(13):1527-32
references.pmid: 16009869
references.citation: Arthritis Rheum. 1997 Mar;40(3):551-61
references.pmid: 9082944
references.citation: Thromb Haemost. 1996 Nov;76(5):651-62
references.pmid: 8950768
references.citation: N Engl J Med. 2003 Jul 10;349(2):109-11
references.pmid: 12853582
references.citation: Blood. 2007 Nov 1;110(9):3097-101
references.pmid: 17684155
references.citation: Thromb Haemost. 2003 Mar;89(3):493-8
references.pmid: 12624633
references.citation: Thromb Res. 1995 Feb 1;77(3):305-10
references.pmid: 7537920
references.citation: Obesity (Silver Spring). 2007 Jan;15(1):216-24
references.pmid: 17228050
references.citation: J Cell Physiol. 1991 Jan;146(1):8-17
references.pmid: 1990021
references.citation: Cancer Control. 2005 Sep;12 Suppl 1:31-7
references.pmid: 16179902
references.citation: Thromb Res. 1997 Jan 15;85(2):159-64
references.pmid: 9058490
references.citation: J Thromb Haemost. 2007 Jul;5 Suppl 1:310-7
references.pmid: 17635742
references.citation: Br J Surg. 1981 Mar;68(3):166-70
references.pmid: 7470818
references.citation: Thromb Haemost. 1996 Apr;75(4):578-84
references.pmid: 8743182
references.citation: Trends Cardiovasc Med. 1995 Jul-Aug;5(4):141-8
references.pmid: 21232251
references.citation: Contraception. 2004 Jul;70(1):3-10
references.pmid: 15208046
references.citation: J Clin Pathol. 1974 Jul;27(7):517-28
references.pmid: 4138834
references.citation: Cancer Metastasis Rev. 1992 Nov;11(3-4):249-66
references.pmid: 1423817
references.citation: Lab Invest. 1982 Nov;47(5):498-504
references.pmid: 6752573
references.citation: Clin Exp Immunol. 1998 May;112(2):325-33
references.pmid: 9649198
references.citation: BMJ. 2007 Jun 23;334(7607):1318-21
references.pmid: 17585161