Review Question - QID 103407

Hemophilia A is an X-linked recessive disease. An affected male will pass the mutated allele to all of his daughters.

Hemophilia A and hemophilia B are both X-linked recessive disorders resulting in indistinguishable phenotypes of excessive bleeding in response to minor trauma, hemarthroses, intramuscular bleeding, and GI bleeding. The mutations responsible for hemophilia A and B cause decreased levels of factor VIII and factor IX clotting factors, respectively (Illustration A). Bleeding episodes can be treated with factor VIII or factor IX concentrate. As an X-linked recessive disease, males require only one mutant copy (either de novo or inherited from the mother's X allele) to manifest the disease. An affected father cannot pass the trait to a son, but will pass the mutated allele to all of his daughters (Illustration B).

Ballas and Kraut review the diagnostic work-up for bleeding and bruising in the primary care setting. Their differential diagnosis for bleeding disorders is divided into quantitative platelet disorders (idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, malignancy, viral disease); functional platelet disorders (Bernard-Soulier syndrome, Glanzmann thrombasthenia, von Willebrand's disease, May-Hegglin anomaly, Wiskott-Aldrich syndrome); hemophilias A and B; acquired hemophilias; hereditary hemorrhagic telangietasia; cryoglobulinemias; leukemias; disseminated intravascular coagulation; and vitamin K deficiency.

Kyaw et al. describe a case series of acquired hemophilia A in which autoantibodies to factor VIII disrupt the coagulation cascade with symptoms similar to those of classic hemophilia A. Because these patients have autoantibodies to the factor VIII concentrate, exogenous factor VII is used for treatment of acute bleeds.

Illustration A is a schematic of the clotting cascade. A defect in either factor VIII or factor IX will result in inadequate generation of thrombin. Illustration B is an example of a pedigree showing an X-linked recessive pattern.

Incorrect Answers:
Answer 1: If the father had 3 unaffected sons, there would be a 0% chance that any son was a carrier.
Answer 2: If two carriers of an autosomal recessive trait have children, there is a 25% chance that any given child will have the trait.
Answer 3: Without knowing the gender of the child in question, there is a 50% chance that the father will pass on the allele to that child.
Answer 4: If two heterozygous parents with an autosomal dominant trait have children, there is a 75% chance that any given child will have the trait (provided that the trait is not homozygous lethal).