14-08: Congenital Disorders of Coagulation

1. HEMOPHILIA A & B

General Considerations

Hemophilia A occurs in ~1 per 5000 live male births, whereas hemophilia B occurs in ~1 in 25,000 live male births. Inheritance is X-linked recessive for both, leading to affected males and carrier (affected) females with variable bleeding tendencies. Daughters of all affected males are obligate carriers. There is no race predilection. Factor activity testing is indicated for male infants with a hemophilic maternal pedigree who are asymptomatic or who experience excessive bleeding, for all daughters of affected males (100% chance of being affected) and carrier mothers (50% chance of being affected), and for otherwise asymptomatic adolescents or adults who experience unexpected excessive bleeding with trauma or invasive procedures.

Inhibitors to factor VIII develop in approximately 20–25% of patients with severe hemophilia A; inhibitors to factor IX develop in less than 5% of patients with severe hemophilia B. Risk of inhibitor formation exists for both plasma-derived and recombinant factor products. The risk of development of an inhibitor to factor VIII or factor IX is highest in patients with severe hemophilia who have a sibling in whom inhibitor formation occurred; the characteristics of initiation of administration of factor replacement in childhood, as well as mutation type, also may be influential. Recent data suggest that recombinant products may have an increased risk of inhibitor formation than products made from pooled plasma.

A substantial proportion of older patients with hemophilia acquired infection with HIV or HCV or both in the 1980s due to exposure to contaminated factor concentrates and blood products.

Clinical Findings

A. Symptoms and Signs

Severe hemophilia (factor VIII activity less than 1%) presents in infants or in early childhood with spontaneous bleeding into joints, soft tissues, or other locations. Spontaneous bleeding is much less common in patients with mild hemophilia (factor VIII activity greater than 5%), but bleeding is common with provoked bleeding (eg, surgery, trauma). Intermediate clinical symptoms are seen in patients with moderate hemophilia (factor VIII activity 1–5%). Female carriers of hemophilia can have a wide range of factor VIII activity and therefore have variable bleeding tendencies.

Significant hemophilic arthropathy can be minimized in patients who receive long-term regular prophylaxis with factor concentrate starting in early childhood, whereas destructive joint disease is common in adults who have experienced recurrent hemarthroses. Patients tend to have one or two “target” joints into which they bleed most often.

Inhibitor development to factor VIII or factor IX is characterized by bleeding episodes that are resistant to ...