Review Question - QID 108270

This clinical presentation is most consistent with an inherited deficiency of coagulation factor VIII, which is also known as hemophilia A.

Hemophilia is an X-linked recessive disorder that is caused by mutation of a coagulation factor in the intrinsic pathway. It often presents in childhood though the age of presentation can be variable based on the degree of factor insufficiency. It classically presents with hemarthroses, intramuscular bleeding, and excessive bleeding to minor trauma. The lab findings characteristic of hemophilia are an isolated increase in PTT due to a defect in the intrinsic pathway without corresponding defects in platelet tests or PT. Hemophilia A is a defect in factor VIII, hemophilia B in factor IX, and hemophilia C in factor XI

The way to approach a question about bleeding disorders on step 1 is to determine whether the bleeding is deep (hemearthroses, muscle bleeding), which is indicative of a coagulation factor deficiency, or superficial (petechiae and purpura), which is indicative of a platelet defect. These suspicions can then be confirmed through the use of lab tests, with PT/PTT being coagulation factor tests and bleeding time / ristocetin cofactor assays being platelet assays. Upon establishing that this patient has an isolated coagulation factor defect, the problem can be localized to the intrinsic pathway (12, 11, 9, 8) because there is a problem with PTT but not with PT. Isolated intrinsic pathway disorders are either genetic hemophilia or autoantibody production disorders and the important test to perform is a mixing study. This study will result in correction of the prolonged PTT when the missing factor is added, in this case factor VIII.

Incorrect Answers:
Answer 1: Bernard-Soulier disease is caused by a genetic defect in the receptor Gp1b, which is used to bind platelets to collagen and von Willebrand factor. It would present with abnormal platelet function tests and have large platelets on histology.
Answer 2: Glanzmann Thrombastheia is caused by a genetic defect in the receptor GpIIb/IIIa, which binds fibrinogen causing platelet crosslinking. Like Bernard-Soulier disease it would have abnormal platelet function tests but would not have big platelets.
Answer 4: Hemophilia B would present identically but would have a correction in PTT upon mixing with factor IX rather than with factor VIII.
Answer 5: Von Willebrand disease can cause an increased PTT because von Willebrand factor is important in stabilizing factor VIII; however, it would present with abnormal platelet function tests in addition to the abnormal PTT.

Family history is extremely important when evaluating unknown sources of excessive bleeding in children because many of these disorders are inherited. The next step is to perform bleeding tests. Vitamin K challenge can also be used in patients who present with increased PT but have normal results otherwise (1).