Chapter 32 Hemophilia
PATHOPHYSIOLOGY
Hemophilia is a congenital blood coagulation disorder in which the child is deficient in clotting factor VIII (hemophilia A) or factor IX (hemophilia B, or Christmas disease). It is an inherited disorder that is transmitted by an X-linked recessive gene from the maternal side. Factor VIII and factor IX are plasma proteins that are necessary components of blood coagulation; they are needed for the formation of fibrin clots at the site of vascular injury. Severe hemophilia results when plasma concentrations of factors VIII and IX are less than 1%. Moderate hemophilia occurs with plasma concentrations between 1% and 5%. In mild hemophilia (severe bleeding only after major trauma and surgery), plasma concentrations are between 6% and 50% of the normal level. The clinical manifestations depend on the child’s age and the severity of the deficiency of factors VIII and IX. Severe hemophilia is characterized by recurrent hemorrhages, occurring either spontaneously or after relatively minor trauma (20 to 30 episodes per year). The most common sites of hemorrhage are the joints, the muscles, and soft tissue. The most common joint sites are the knees, the elbows, the ankles, the shoulders, and the hips. The muscles most often affected are the forearm flexor, the gastrocnemius, and the iliopsoas. Bleeding into the joint or muscle can lead to pain, limited mobility, need for ongoing physical therapy, and some degree of impaired functioning. Life-threatening bleeding episodes can occur in the brain, the gastrointestinal tract, and the neck and throat. Because of improvements in treatment, almost all individuals with hemophilia are expected to live a normal life span. Preliminary data from experimental gene therapy are promising.
INCIDENCE
1. Incidence is 1 in 5000 male births.
2. Incidence of hemophilia A is 20.6 in 100,000.
3. Incidence of hemophilia B is 5.3 in 100,000.
4. Mild hemophilia (5% to 49% factor activity) has bleeding episodes after trauma or surgery.
5. Moderate hemophilia (1% to 5% factor activity) has bleeding after stress or overuse injury to joints or muscles.
6. Severe hemophilia (<1% factor activity) has bleeding with the above in addition to spontaneous bleeding.
7. The family histories of two thirds of affected children reveal an X-linked recessive form of inheritance.
8. About 30% of cases are the result of new mutations.
9. Central nervous system bleeding occurs in 3% of affected children.
10. Spontaneous bleeding and posttraumatic intracranial bleeding are associated with a 34% mortality rate and a 50% rate of long-term morbidity.
11. Of individuals with hemophilia A and hemophilia B, 10% develop immunoglobulin G antibodies that inhibit the activity of factors VIII and IX.
