A 24-year-old woman presents to her physician with a lifelong history of easy bruising and prolonged bleeding after dental extractions. She also reports increasingly heavy menstrual periods that last 8 to 9 days and require frequent pad changes. Her father has a similar history of frequent nosebleeds. Vital signs are within normal limits. Physical examination is unremarkable except for several small ecchymoses on her shins.
Laboratory studies show the following:
Hemoglobin: 11.5 g/dL
Platelet count: 210,000/μL
Prothrombin Time (PT): 12 seconds (Normal: 11–13.5s)
Partial thromboplastin time (PTT): 38 seconds (Normal: 25–35s)
Bleeding time: Prolonged
Which of the following is the most likely primary defect in this patient?
The correct answer is:
A) Deficiency of a plasma protein required for platelet adhesion
This patient is presenting with von Willebrand Disease (vWD), the most common inherited bleeding disorder. von Willebrand Factor (vWF) is a multimeric glycoprotein that serves two essential roles in hemostasis:
Platelet Adhesion: It acts as a molecular bridge between platelet Glycoprotein Ib (GP Ib) receptors and the exposed subendothelial collagen at the site of vascular injury.
Factor VIII Carrier: It binds to and stabilizes Factor VIII, protecting it from rapid degradation in the plasma.
The classic presentation of vWD involves mucocutaneous bleeding (epistaxis, menorrhagia, easy bruising) and an autosomal dominant inheritance pattern. Because vWF stabilizes Factor VIII, a deficiency in vWF can lead to a secondary decrease in Factor VIII levels, which explains why the PTT may be mildly prolonged in some patients. However, the PT remains normal because the extrinsic pathway is unaffected.
Answer choice B: Failure of platelet aggregation due to lack of GP IIb/IIIa, is incorrect. This describes Glanzmann thrombasthenia. While it also causes mucocutaneous bleeding and a prolonged bleeding time, it is an autosomal recessive disorder and would show a failure of platelets to aggregate with all agonists except ristocetin.
Answer choice C: Impaired cross-linking of fibrin by Factor XIII, is incorrect. Factor XIII deficiency results in delayed bleeding and poor wound healing. However, since Factor XIII acts at the very end of the coagulation cascade, both the PT/PTT and the bleeding time/platelet function tests would be normal.
Answer choice D: Inability of platelets to adhere due to lack of GP Ib, is incorrect. This describes Bernard-Soulier Syndrome. While the mechanism is similar to vWD (disrupted adhesion), the defect is in the platelet receptor itself, not the plasma protein (vWF). Bernard-Soulier is also characterized by thrombocytopenia and giant platelets on the peripheral smear.
Answer choice E: Qualitative defect in the stabilization of the Factor IX complex, is incorrect. Factor IX is involved in Hemophilia B (Christmas Disease), which typically presents with deep tissue bleeding (hemarthrosis) rather than mucocutaneous bleeding. vWF stabilizes Factor VIII, not Factor IX.
Key Learning Point
von Willebrand Disease is characterized by a defect in platelet adhesion and a secondary deficiency of Factor VIII. Laboratory findings typically include a prolonged bleeding time (or abnormal PFA-100) and a normal or mildly prolonged PTT, with a normal PT and platelet count. The diagnosis is confirmed by a low ristocetin cofactor assay, which measures vWF-induced platelet agglutination.
