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Genetics of the hemophilias

W Keith Hoots, MD
Amy D Shapiro, MD
Section Editors
Lawrence LK Leung, MD
Donald H Mahoney, Jr, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD


The hemophilias are a group of related bleeding disorders that usually are inherited. Inherited bleeding disorders include abnormalities of coagulation factors as well as platelet function, the most common of which is von Willebrand disease. However, when the term "hemophilia" is used, it usually refers specifically to the following two disorders:

Factor VIII deficiency (hemophilia A) – Hemophilia A affects 1 in 5000 to 10,000 males; roughly 60 percent have severe disease, with factor VIII activity less than 1 percent of normal.

Factor IX deficiency (hemophilia B) – Hemophilia B affects 1 in 25,000 to 30,000 males; approximately one-half have mild to moderate disease, with factor IX activity greater than 1 percent of normal.

Severe factor VIII or factor IX deficiency leads to bleeding because of the role these factors play in the intrinsic pathway X-ase (ten-ase). The X-ase complex consists of activated factor IX (factor IXa) as the protease; activated factor VIII (factor VIIIa), calcium, and phospholipids as the cofactors; and factor X as the substrate (figure 1) [1]. (See "Overview of hemostasis", section on 'Multicomponent complexes' and "Biology and normal function of factor VIII and factor IX".)

This topic reviews the genetic basis of Hemophilia A and B. Diagnosis and management of patients with hemophilia are discussed separately.

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Literature review current through: Nov 2017. | This topic last updated: Feb 02, 2017.
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