Factor XII
Template:PBB Hageman factor is a plasma protein also known as factor XII. It is the zymogen form of factor XIIa, an enzyme (EC 3.4.21.38) of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the F12 gene.[1]
Function
It is part of the coagulation cascade and activates factor XI and prekallikrein. Factor XII itself is activated to factor XIIa by negatively charged surfaces, such as glass.[2]
Genetics
The gene for factor XII is located on the tip of the long arm of the fifth chromosome (5q33-qter).[1]
Role in disease
Hageman factor deficiency is a rare hereditary disorder with a prevalence of about one in a million, although it is a little less common among Asians. Deficiency does not cause excessive hemorrhage due to an apparent lack of involvement of the activated form of the zymogen, factor XIIa in thrombin formation. However, it may increase the risk of thrombosis, due to inadequate activation of the fibrinolytic pathway. The deficiency leads to activated partial thromboplastin times (PTT) greater than 200 seconds.
Two missense mutations have been identified in F12, the gene encoding human coagulation factor XII. These mutations are thought to be the cause of a very rare form of hereditary angioedema (HAE), called HAE type III.[3]
History
Hageman factor was first discovered in 1955 when a routine preoperative blood sample of the 37-year-old railroad brakeman John Hageman was found to have prolonged clotting time in test tubes, even though he had no hemorrhagic symptoms. Hageman was then examined by Dr. Oscar Ratnoff who found that Mr. Hageman lacked a previously unidentified clotting factor.[4] Dr. Ratnoff later found that the Hageman factor deficiency is autosomal recessive disorder, when examining several related people which had the deficiency. Paradoxically, pulmonary embolism contributed to Hageman's death after an occupational accident. Since then, case series clinical studies have identified an association of thrombosis and Factor XII deficiency, though the pathophysiology of the relationship is unclear. Hepatocytes express blood coagulation factor XII.[5]
References
- ^ a b Cool DE, MacGillivray RT (1987). "Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region". J. Biol. Chem. 262 (28): 13662–73. PMID 2888762.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Encyclopedia Britannica Online, accessed 28/7/08
- ^ Cichon S, Martin L, Hennies HC; et al. (2006). "Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III". Am. J. Hum. Genet. 79 (6): 1098–104. doi:10.1086/509899. PMID 17186468.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Ratnoff OD, Margolius A (1955). "Hageman trait: an asymptomatic disorder of blood coagulation". Trans. Assoc. Am. Physicians. 68: 149–54. PMID 13299324.
- ^ Gordon EM, Gallagher CA, Johnson TR, Blossey BK, Ilan J (1990). "Hepatocytes express blood coagulation factor XII (Hageman factor)". J. Lab. Clin. Med. 115 (4): 463–9. PMID 2324612.
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Further reading
External links
- Factor+XII at the U.S. National Library of Medicine Medical Subject Headings (MeSH)