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GENERAL ASPECTS

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  • 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 and dramatically accelerating 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 (Fig. 79–1). Approximately 30 percent 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.

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FIGURE 79–1

Inheritance 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, 8th ed, Chap. 124, Fig. 124–1, p. 2010.)

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HEMOPHILIA A

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Clinical Features

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  • Table 79–1 shows a clinical classification of hemophilia A based on factor VIII levels.

  • Hemostasis is generally normal with levels in excess of 30 percent.

  • The factor VIII level remains constant throughout the patient's life, and is similar in other affected members of the kindred, but varies between kindreds.

  • Hemarthrosis accounts for 75 percent 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 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 (Fig. 79–2).

  • Hematomas may develop after bleeding into muscles or ...

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