Factor XII deficiency is a deficiency in the production of

factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struc ...

(FXII), a plasma glycoprotein and clotting factor that participates in the

coagulation cascade Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism ...

and activates

factor XI Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the ''F11'' gene. ...

. FXII appears to be not essential for blood clotting, as individuals with this condition are usually asymptomatic and form blood clots

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

. FXII deficiency tends to be identified during presurgical laboratory screening for bleeding disorders. The condition can be inherited or acquired.

Symptoms and signs

While it is indicated that people with FXII deficiency are generally asymptomatic, studies in women with

recurrent miscarriage Recurrent miscarriage is three or more consecutive pregnancy losses. In contrast, infertility is the inability to conceive. In many cases the cause of RPL is unknown. After three or more losses, a thorough evaluation is recommended by American S ...

s suggest an association with FXII deficiency. The condition is of importance in the differential diagnosis to other bleeding disorders, specifically the hemophilias: hemophilia A with a deficiency in factor VIII or antihemophilic globulin, hemophilia B with a deficiency in factor IX (Christmas disease), and hemophilia C with a deficiency in factor XI. Other rare forms of bleeding disorders are also in the differential diagnosis. There is concern that individuals with FXII deficiency are more prone to thrombophilic disease, however, this is at variance with a long-term study from Switzerland.

Causes

Inherited or congenital FXII deficiency is usually passed on by autosomal recessive inheritance. A person needs to inherit a defective gene from both parents. People who have only one defective gene are asymptomatic, but may have lower FXII levels and can pass the gene on to half their offspring. In persons with congenital FXII deficiency the condition is lifelong. People affected may want to alert other family members as they may also carry the gene. A 1994 study of 300 healthy blood donors found that 7 persons (2.3%) had FXII deficiencies with one subject having no detectable FXII (0.3%). This study is at variance with estimates that only 1 in 1,000,000 people has the condition. The acquired form of FXII deficiency is seen in patients with the nephrotic syndrome, liver disease,

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

and shock, disseminated intravascular coagulation, and other diseases.

Diagnosis

The condition is diagnosed by blood tests in the laboratory when it is noted that special blood clotting test are abnormal. Specifically Activated Partial Thromboplastin Time (aptt) is prolonged. The diagnosis is confirmed by an assay detecting very low or absent FXII levels. The FXII (F12) gene is found on chromosome 5q33-qter. In

hereditary angioedema Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomitin ...

type III an increased activity of factor XII has been described.

Treatment

In congenital FXII deficiency treatment is not necessary. In acquired FXII deficiency the underlying problem needs to be addressed.

History

The condition was first described in 1955 based by blood testing of a patient named John Hageman.

References

External links

{{Diseases of megakaryocytes, us=y Bleeding Coagulopathies