Factor xii deficiency

Factor XII Deficiency

Factor XII deficiency, also known as Hageman factor deficiency, is a rare genetic disorder that affects the blood coagulation process. It is characterized by a deficiency of Factor XII, a protein involved in the initiation of the intrinsic pathway of blood coagulation. Despite the deficiency, individuals with this condition typically do not experience abnormal bleeding, which makes it unique among coagulation disorders.

Pathophysiology

Factor XII is a serine protease that plays a crucial role in the coagulation cascade. It is activated upon contact with negatively charged surfaces, such as subendothelial collagen, and subsequently activates Factor XI, leading to a cascade of reactions that result in the formation of a blood clot. In Factor XII deficiency, the initial activation of the intrinsic pathway is impaired, but this does not usually result in a bleeding tendency. This is because the extrinsic pathway, initiated by tissue factor, can compensate for the lack of intrinsic pathway activation.

Genetics

Factor XII deficiency is inherited in an autosomal recessive manner. The gene responsible for encoding Factor XII is located on chromosome 5 (5q33-qter). Mutations in this gene lead to reduced levels or activity of Factor XII in the blood. Homozygous individuals typically have very low levels of Factor XII, while heterozygous individuals may have moderately reduced levels.

Clinical Presentation

Most individuals with Factor XII deficiency are asymptomatic and are often diagnosed incidentally during routine coagulation screening tests, such as the activated partial thromboplastin time (aPTT), which is prolonged. Despite the prolonged aPTT, these individuals do not usually have a bleeding disorder. In fact, some studies suggest that Factor XII deficiency may be associated with an increased risk of thrombosis, although this is not well established.

Diagnosis

The diagnosis of Factor XII deficiency is typically made through laboratory testing. A prolonged aPTT with normal prothrombin time (PT) and thrombin time (TT) suggests a defect in the intrinsic pathway. Specific assays measuring Factor XII activity can confirm the diagnosis. Genetic testing can identify mutations in the F12 gene.

Management

Since Factor XII deficiency does not usually cause bleeding, no specific treatment is required. Management focuses on monitoring and addressing any thrombotic risks if they arise. In surgical or invasive procedures, standard precautions are usually sufficient, as bleeding complications are not expected.

Prognosis

The prognosis for individuals with Factor XII deficiency is excellent, as they do not typically experience bleeding complications. However, the potential association with thrombosis warrants further investigation and monitoring.

Also see

• Coagulation cascade
• Hemophilia
• Von Willebrand disease
• Thrombophilia