History:

A 3-year-old boy is noted to have increasing difficulty with movement, even walking, due to increasing pain and diminished joint mobility. His knees, ankles, and elbows seem to be affected the most. When he suffers even a small scratch or cut, bleeding continues for more than 20 minutes. A hematoma forms with minimal trauma. Wound healing is poor. On physical examination, joints of extremities show diminished range of motion. No petechial hemorrhages or ecchymoses are noted. The remainder of the exam is normal.

Questions:

1. What is the inheritance pattern for this genetic disease?

Hemophilia A is an X-linked recessive. A less common but similar (though more likely not as severe) bleeding disorder is known as hemophilia B, with a similar inheritance pattern.

2. What is the basis for this genetic disease?

In most cases there is a functional deficiency of factor VIII with lack of adequate factor VIII activity. In a minority of cases, actual levels of factor VIII are decreased. Factor VIII normally circulates in the plasma bound to a much larger molecule, the von Willebrand factor (VWF), as part of the factor VIII complex. In hemophilia B, there is a lack of factor IX. The lack of factor or factor activity determines the severity of the disease.

3. What laboratory testing will help to identify this disease?

The abnormal PTT and normal PT, along with normal platelet count, help to narrow down the possibilities, suggesting a problem with a clotting factor in the intrinsic pathway of coagulation. Measurement of factor VIII and factor VIII activity is used to make the diagnosis.

Detection of carriers is more complex. Measurement of levels of VWF are normal or increased in carriers of hemophilia A, whether a deficiency of factor VIIIc can be found. The ratio of VIIIc to VWF is normally 0.74 to 2.2, but ranges from 0.18 to 0.9 in known carriers. The overall detection rate is 72 to 94% in such obligatory carriers but only 48 to 51% in women without a family history.

4. What is the organ involvement of this disease?

The most characteristic bleeding manifestation is hemarthrosis, which often develops despite significant trauma. Frequency and severity of bleeding is related to the blood level of factor VIIIc. An arthropathy with joint ankylosis eventually develops.

Patients can have bleeding into soft tissues with hematoma formation. Hematomas in the head and neck region can compromise the airways. Hematomas may impinge upon vital structures such as blood vessels and nerves.

5. What is the prognosis for this disease?

Use of factor VIII concentrate has improved the prognosis so that a nearly normal life span is possible, with lessened disability from hemarthroses. Factor VIII concentrates are now manufactured without the risk for transmission of infectious diseases (such as hepatitis or HIV).