Hageman factor deficiency, also known as factor XII deficiency, is a rare genetic blood disorder that causes prolonged clotting (coagulation) of blood in a test tube without the presence of prolonged clinical bleeding tendencies. It is caused by a deficiency of the Hageman factor (factor XII), a plasma protein (glycoprotein). Although it is thought that factor XII is needed for blood clotting, when it is deficient, other blood clotting factors tend to compensate for its absence. This disorder is thought to be benign and usually presents no symptoms (asymptomatic); it is usually only accidentally discovered through pre-operative blood tests that are required by hospitals. Of substantial recent interest is the role of antibodies to Factor XII in recurrent pregnancy losses. .
Hageman factor deficiency is rarely associated with any symptoms. However, when blood from a patient is subjected to a partial thromboplastin time test (PTT), a test measuring clotting time, it takes an abnormally long time for the blood to clot. Serum prothrombin time, another test of blood clotting, is also abnormally long. The blood level of Hageman factor (factor XII) tends to vary greatly.
According to some researchers, Hageman factor deficiency may predispose affected individuals to developing blood clots (thrombi) at an early age. Another reported result of Hageman factor deficiency is inflammation of the vein associated with a blood clot (thrombophlebitis). However, other researchers have challenged this theory and it remains unproven what, if any, role Hageman factor deficiency has in the development of blood clots.
Hageman factor deficiency is inherited as an autosomal recessive disorder. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent.
Investigators have determined that Hageman factor deficiency occurs due to mutations of the F12 gene located on the long arm of chromosome 5. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 5q33" refers to band 33 on the long arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Hageman factor deficiency affects persons of Asian descent more often than individuals of other ethnicities. Males and females are affected in equal numbers. Since no symptoms are usually associated with Hageman factor deficiency, many individuals remain undiagnosed. The exact incidence of the disorder in the general population is unknown, but estimated to be approximately 1 in 1 million individuals.
Symptoms of the following disorders can be similar to those of Hageman factor deficiency. Comparisons may be useful for a differential diagnosis:
Factor IX deficiency is a severe genetic bleeding disorder that resembles classic hemophilia A, although it occurs only one-fifth as often as hemophilia. Factor IX is a component of the blood clotting substance, thromboplastin; it is deficient at birth in patients with this disorder. Factor IX deficiency varies in severity and occurs most often in males. In rare instances, female carriers have been known to exhibit this deficiency in a mild form. Symptoms include prolonged bleeding episodes, and in very severe cases, joint pain and bone deformities. (For more information on this disorder, choose "Factor IX" as your search term in the Rare Disease Database.)
Factor XIII deficiency is an extremely rare genetic bleeding disorder. It is characterized by slow, oozing internal bleeding occurs several days after mild or severe injury. Poor wound healing and excessive bleeding from wounds are less common symptoms. About 100 cases of Factor XIII deficiency have been described in the medical literature. Males and females are affected equally. With treatment, patients with this disorder can expect to live a normal life span. Without treatment, however, intracranial bleeding may eventually be life threatening. (For more information on this disorder, choose "Factor XIII" as your search term in the Rare Disease Database.)
Diagnosis Hageman factor deficiency is often diagnosed accidentally during a routine blood clotting (coagulation) tests as in one done before surgery. In affected individuals, it will take longer for their blood to clot during these tests. Further tests can reveal low levels of factor XII in the blood.
Treatment Treatment for this disorder is usually not necessary since the bleeding is only mild.
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:904-05.
REVIEW ARTICLES Sugi T, Makino T. Autoantibodies to contact proteins in patients with recurrent pregnancy losses. J Reprod Immunol. 2002;53:269-77.
Baker WF Jr, Bick RL. Treatment of hereditary and acquired thrombophilic disorders. Semin Thromb Hemost. 1999;25:387-406.
JOURNAL ARTICLES Jones DW, Gallimore MJ, Winter M. Recurerent abortion-antibodies to factor XII or a decrease in factor XII levels? Fertil Steril. 2001;76:1288-89.
Ogasawara MS, Iinuma Y, Aoki K, et al. Low-dose aspirin is effective for treatment of recurrent miscarriage in patients with decreased coagulation factor XII. Fertil Steril. 2001;76:203-04.
Matsuura T, Kobayashi T, Asahina T, et al. Is factor XII deficiency related to recurrent miscarriage. Semin Thromb Hemost. 2001;27:115-20.
Helft G, Le Feuvre C, Metzger JP, et al. Factor XII deficiency associated with coronary stent thrombosis. Am J Hematol. 2000;64:322-23.
Zeerleder S, Schloesser M, Redondo M, et al. Reevaluation of the incidence of thromboembolic complications in congenital Factor XII deficiency-a study on 73 subjects from 14 Swiss families. Thromb Haemost. 1999;82:1240-46.
FROM THE INTERNET Matsui W. MEDLINEplus. Medical Encyclopedia. Factor XII (Hageman factor) deficiency. Last Update: 02/26/07. Available at: www.nlm.nih.gov/medlineplus/ency/article/000545.htm Accessed On: February 28, 2008.
Canadian Hemophilia Society. Factor XII Deficiency. An Inherited Bleeding Disorder 2004:12pp. Available at: http://www.hemophilia.ca/en/pdf/13/FactorXII_E.pdf Accessed On: February 22, 2008.
National Hemophilia Foundation 116 West 32nd Street 11th Floor New York, NY 10001 USA Tel: (212)328-3737 Fax: (212)328-3795 Tel: (800)424-2634 Email: gwidlundDhemophilia.org Internet: http://www.hemophilia.org
Canadian Hemophilia Society 625 President Kennedy Suite 505 Montreal Quebec, H3A 1K2 Canada Tel: 5148480503 Fax: 5148489661 Tel: 8006682686 Email: chs@hemophilia.ca Internet: http://www.hemophilia.ca
NIH/National Heart, Lung and Blood Institute Information Center P.O. Box 30105 Bethesda, MD 20824-0105 Tel: (301)592-8573 Fax: (301)251-1223 Email: nhlbiinfo@rover.nhlbi.nih.gov
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