Chapter 78: Hemophilia A and B

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.

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 ...