The Molecular Genetics of Hemophilia A and B in Man

Factor VIII and Factor IX Deficiency
  • Stylianos E. Antonarakis
Part of the Advances in Human Genetics book series (AHUG, volume 17)


Hemophilias are relatively common inherited disorders of blood coagulation arising from deficiency of two different clotting factors VIII and IX. Hemophilia A, or classic hemophilia, is associated with abnormality of factor VIII and affects about 1 in every 10,000 males; hemophilia B, or Christmas disease, is associated with abnormality of factor IX and affects about 1 in every 50,000 males (McKee, 1983). Both factors are involved in the middle phase of the intrinsic clotting cascade, which consists of several inactive proteases and cofactors that are serially activated in response to an initial stimulus. The end product of the cascade is the production of the insoluble fibrin from the soluble protein fibrinogen. Fibrin then forms a filamentous network and stabilizes the platelet plug. Factor IX is a serine protease, which after proteolytic cleavage by factor XIa becomes activated (IXa) and with the help of factor VIII:Ca, Ca2+, and phospholipid activates factor X. Factor VIII in its “activated” form VIII:Ca is actually a cofactor for the activation of factor X [see Jackson and Nemerson (1980) for review].


Factor VIII Prenatal Diagnosis Severe Hemophilia Carrier Detection Clotting Factor VIII 
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© Plenum Press, New York 1988

Authors and Affiliations

  • Stylianos E. Antonarakis
    • 1
  1. 1.Genetics Unit, Department of PediatricsThe Johns Hopkins University School of MedicineBaltimoreUSA

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