Hemophilia, a hereditary bleeding disorder, results from a deficiency of specific clotting factors. The severity of bleeding and the prognosis vary with the degree of deficiency, or nonfunction, and the site of bleeding. Hemophilia occurs in 20 of 100,000 male births.
Hemophilia A (classic hemophilia) results from a deficiency of factor VIII. More common than type B, it affects more than 80% of all hemophiliacs and is the most common X-linked genetic disease. Hemophilia B (Christmas disease) affects approximately 15% of all hemophiliacs and results from a deficiency of factor IX.
Advances in treatment have greatly improved the prognosis for hemophiliacs, many of whom live normal life spans. Surgical procedures can be done safely at special treatment centers under the guidance of a hematologist.
Causes
Hemophilia types A and B: X-linked recessive genetic traits
Pathophysiology
Hemophilia is an X-linked recessive genetic disease causing abnormal bleeding because of a specific clotting factor malfunction. Factors VIII and IX are components of the intrinsic clotting pathway; factor IX is an essential factor and factor VIII is a critical cofactor that accelerates the activation of factor X by several thousandfold. Excessive bleeding occurs when these clotting factors are reduced by more than 75%. A deficiency or nonfunction of factor VIII causes hemophilia A, and a deficiency or nonfunction of factor IX causes hemophilia B.
Hemophilia may be severe, moderate, or mild, depending on the degree of activation of clotting factors. Patients with severe disease have no detectable factor VIII or factor IX activity. Moderately afflicted patients have 1% to 4% of normal clotting activity, and mildly afflicted patients have 5% to 25% of normal clotting activity.
A patient with hemophilia forms a platelet plug at a bleeding site, but clotting factor deficiency impairs the ability to form a stable fibrin clot. Bleeding occurs primarily into large joints, especially after trauma or surgery. Delayed bleeding is more common than immediate hemorrhage. Spontaneous intracranial bleeding may be fatal.
Signs and symptoms
· Spontaneous bleeding in severe hemophilia (prolonged or excessive bleeding after circumcision is often the first sign)
· Excessive or continued bleeding or bruising after minor trauma or surgery
· Large subcutaneous and deep I.M. hematomas due to mild trauma
· Prolonged bleeding in mild hemophilia after major trauma or surgery, but no spontaneous bleeding after minor trauma
· Pain, swelling, and tenderness due to bleeding into joints (especially weight-bearing joints)
· Internal bleeding, often manifested as abdominal, chest, or flank pain
· Hematuria
· Hematemesis or tarry stools
Diagnostic test results
· Specific coagulation factor assays show the type and severity of hemophilia.
· Laboratory analysis reveals low serum factor VIII activity of normal and prolonged activated partial thromboplastin time (hemophilia A).
· Laboratory analysis reveals deficient factor IX and normal factor VIII levels (hemophilia B).
Treatment
· Cryoprecipitate (for hemophilia A) or lyophilized factor VIII or IX to increase clotting factor levels and to permit normal hemostasis levels
· Factor IX concentrate during bleeding episodes (hemophilia B)
· Aminocaproic acid (Amicar) for oral bleeding (inhibits plasminogen activator substances)
· Prophylactic desmopressin before dental procedures or minor surgery to release stored von Willebrand's factor and factor VIII (to reduce bleeding)
· Fresh frozen plasma
· Immunization with hepatitis B vaccine
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NORMAL CLOTTING AND CLOTTING IN HEMOPHILIA
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Clinical Tip
X-Linked Recessive Inheritance
The diagram shows the children of a normal parent and those of a parent with a recessive gene on the X chromosome (shown by an open dot). All daughters of an affected male will be carriers. The son of a female carrier may inherit a recessive gene on the X chromosome and be affected by the disease. Unaffected sons can't transmit the disorder.
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