Hemophilia A vs. von Willebrand disease
Hemophilia A is an X-linked recessive deficiency of coagulation factor VIII that causes deep bleeding into joints and muscles, while von Willebrand disease is a usually autosomal dominant defect of von Willebrand factor that impairs platelet adhesion and causes mucocutaneous bleeding.
Both disorders involve factor VIII, which is why they are so often confused. Hemophilia A is a quantitative or qualitative deficiency of factor VIII itself. Von Willebrand disease is a deficiency or dysfunction of von Willebrand factor (vWF), a protein with two jobs: it bridges platelets to exposed subendothelial collagen, and it acts as the carrier that stabilizes circulating factor VIII. Losing vWF therefore causes both a platelet adhesion defect and a secondary drop in factor VIII levels.
Inheritance and epidemiology differ sharply. Hemophilia A is X-linked recessive, so it presents almost exclusively in males, with about a third of cases arising from new mutations. Von Willebrand disease is most commonly autosomal dominant, affects both sexes equally, and is the most common inherited bleeding disorder overall — though many cases are mild enough to go undiagnosed.
The bleeding patterns follow the mechanism. Hemophilia A produces deep bleeding: hemarthrosis, intramuscular hematoma, and delayed or prolonged bleeding after surgery or trauma. Von Willebrand disease produces mucocutaneous bleeding: epistaxis, easy bruising, gingival bleeding, and menorrhagia. On laboratory testing, hemophilia A shows a prolonged PTT with normal PT, platelet count, and bleeding time. Von Willebrand disease shows a prolonged bleeding time with normal platelet count, PT normal, and PTT normal or prolonged depending on how far factor VIII has fallen; the ristocetin cofactor assay is abnormal and ristocetin-induced platelet aggregation is decreased. Desmopressin, which releases stored vWF from endothelium, is useful in mild hemophilia A and in most type 1 von Willebrand disease; severe hemophilia A requires factor VIII replacement.
This comparison is a classic USMLE Step 1 question format. The exam typically supplies a coagulation panel and a bleeding pattern and asks for the diagnosis, so anchor on the pairing: prolonged PTT with deep joint bleeding points to hemophilia A, while prolonged bleeding time with mucosal bleeding and an abnormal ristocetin assay points to von Willebrand disease.
Key takeaways
- Hemophilia A is X-linked recessive factor VIII deficiency; von Willebrand disease is usually autosomal dominant vWF deficiency.
- vWF mediates platelet adhesion and carries factor VIII, so its loss produces both platelet and coagulation defects.
- Hemophilia A causes deep bleeding such as hemarthrosis; von Willebrand disease causes mucocutaneous bleeding.
- Hemophilia A: prolonged PTT, normal bleeding time. Von Willebrand disease: prolonged bleeding time, abnormal ristocetin cofactor assay.
- Desmopressin treats mild hemophilia A and most type 1 von Willebrand disease; severe hemophilia A needs factor VIII replacement.