Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ GENERAL ASPECTS ++ Hemophilia A and hemophilia B are caused by inherited deficiencies of factor VIII and factor IX, respectively. Both result from decreased production of the deficient factor, production of a factor with decreased functional activity, or a combination of these two abnormalities. The activated form of factor IX, factor IXa, is a serine protease that functions to activate factor X. Activated factor VIII, factor VIIIa, serves as a cofactor, forming a complex with factor IXa on the platelet surface, that dramatically accelerates the rate of factor X activation by factor IXa. In patients with hemophilia, clot formation is delayed because thrombin generation is markedly decreased. The clot that does form is hemostatically ineffective, leading to excessive bleeding. Because deficiency of either factor VIII or factor IX causes an inability to activate factor X, the clinical characteristics and approach to treatment of hemophilia A and hemophilia B are similar. Both hemophilia A and B are X-linked recessive disorders, affecting only males, with rare exceptions (Figure 78–1). Approximately 30% of mutations arise de novo. Hemophilia is found worldwide in all ethnic groups. Hemophilia A is estimated to occur in 1 of 10,000 male births and hemophilia B in 1 of 25,000 to 30,000 male births. ++ FIGURE 78–1Inheritance pattern of hemophilia A. X is normal; Xh has an abnormal X chromosome with the hemophilic gene; Y is normal; XX is a normal female; XY is a normal male; XXh is a carrier female; XhY is a hemophilic male. (Source: Williams Hematology, 9th ed, Chap. 123, Fig. 123–1.) Graphic Jump LocationView Full Size|Favorite Figure|Download Slide (.ppt) ++ HEMOPHILIA A ++ Clinical Features ++ Table 78–1 shows a clinical classification of hemophilia A based on factor VIII levels. Hemostasis is generally normal with levels in excess of 30%. The factor VIII level remains constant throughout the patient’s life, and it is similar in other affected members of the kindred but varies between kindreds. Hemarthrosis accounts for 75% of bleeding episodes in patients with severe hemophilia A. The most frequent sites are the knees, followed by the elbows, ankles, shoulders, wrists, and hips. The acute form of hemarthrosis is characterized by initial mild pain without physical findings, followed by more intense pain, swelling and warmth of the joint, and decreased range of motion. The patient may have mild fever. Significant or sustained fever suggests infection in the joint. When bleeding stops, the blood resorbs and symptoms subside over several days. Repeated bleeding into the joint results in synovial hypertrophy and inflammation, with limitation of motion and a tendency for more frequent bleeding in that joint (target joint). Eventually, repeated hemorrhage into the joints causes destruction of the articular cartilage, synovial hyperplasia, and joint deformity with muscle atrophy and soft tissue contractures (Figure 78–2). Hematomas may develop after bleeding into muscles or subcutaneous tissues (... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!