A 12-year-old girl is investigated for heavy menstrual bleeding since menarche and easy bruising; her mother also has menorrhagia and a maternal uncle bleeds excessively after dental work. On testing, the platelet count is normal but the bleeding time is prolonged, the activated partial thromboplastin time is prolonged, the prothrombin time is normal, ristocetin-induced platelet aggregation is impaired, and factor VIII activity is reduced to about half of normal. What is the diagnosis?
- A.Von Willebrand disease
- B.Haemophilia A
- C.Bernard-Soulier syndrome
- D.Glanzmann thrombasthenia
Show answer and explanation
Answer: A. Von Willebrand disease
Correct answer: A. Von Willebrand disease.
The combination of mucocutaneous bleeding (menorrhagia, easy bruising), a prolonged bleeding time, prolonged aPTT with normal PT, impaired ristocetin-induced aggregation and a secondary fall in factor VIII is classic von Willebrand disease. Von Willebrand factor (vWF) does two jobs: it bridges platelets to subendothelium (so its deficiency prolongs the bleeding time and blunts ristocetin aggregation) and it chaperones factor VIII in plasma (so low vWF lowers factor VIII, prolonging the aPTT). The autosomal, both-sexes inheritance fits too.

vWF bridges platelets and carries factor VIII; its lack causes this mixed picture.
Incorrect Options:
- B. Haemophilia A: X-linked, affects males, gives deep joint and muscle bleeds with a normal bleeding time and normal ristocetin aggregation.

Haemophilia A: deep haemarthroses, normal bleeding time; ristocetin normal. - C. Bernard-Soulier syndrome: GPIb defect gives giant platelets and thrombocytopenia; ristocetin fails but factor VIII is normal.

Bernard-Soulier: giant platelets, low count; factor VIII is not reduced. - D. Glanzmann thrombasthenia: GPIIb/IIIa defect; aggregation fails to all agonists but ristocetin agglutination is preserved and factor VIII is normal.

Glanzmann: absent aggregation to ADP but intact ristocetin; factor VIII normal.
High-Yield Facts:
- Von Willebrand disease is the commonest inherited bleeding disorder, autosomal dominant.
- vWF stabilises factor VIII, so severe deficiency lowers factor VIII secondarily.
- Ristocetin cofactor activity assay is the key functional test.
- Desmopressin (DDAVP) raises vWF and factor VIII in type 1 disease.







