A 16-year-old female with frequent nosebleeds and menorrhagia has normal platelet count, prolonged aPTT, abnormal PFA-100 with ristocetin, and platelets that show no aggregation with ristocetin but normal responses to ADP, collagen, and epinephrine. This is most consistent with which disorder?

• A. Christmas disease
• B. Hemophilia A
• C. Glanzmann thrombasthenia
• D. von Willebrand disease

Answer: (D)

The key idea is a bleeding disorder that impairs platelet adhesion due to deficiency or dysfunction of von Willebrand factor. In von Willebrand disease, platelets can respond normally to ADP, collagen, and epinephrine, so overall platelet function tests for those pathways look normal. What changes is the interaction between platelets and damaged vessel walls: von Willebrand factor normally binds exposed collagen and bridges platelets to the vessel wall via the GPIb receptor. When vWF is deficient or defective, this ristocetin-mediated adhesion is impaired.

That’s why the ristocetin-induced platelet aggregation is absent and the PFA-100 test using ristocetin is abnormal. Prolonged aPTT also fits, because vWF stabilizes factor VIII; with reduced vWF, factor VIII activity falls and the intrinsic pathway time is extended. Clinically, mucocutaneous bleeding such as epistaxis and menorrhagia in a teenage girl further supports this diagnosis.

Other disorders don’t fit as well. A factor IX deficiency would prolong aPTT but would not produce abnormal ristocetin responses or mucocutaneous bleeding patterns typical of vWD. Glanzmann thrombasthenia shows defective aggregation with ADP, collagen, and epinephrine due to GPIIb/IIIa deficiency, while ristocetin-induced aggregation remains intact. Bernard-Soulier syndrome causes abnormal ristocetin testing but also presents with thrombocytopenia and giant platelets, unlike this normal platelet count.