SN3 SHORT NOTE 5M ★ High-yield

Describe von Willebrand disease and differentiate it from haemophilia A.

Pathology · 2nd Professional — Para-Clinical

Definition

Von Willebrand disease is an inherited deficiency or dysfunction of von Willebrand factor (vWF), and is the commonest inherited bleeding disorder, affecting up to 1% of the population.

Functions of Von Willebrand Factor

1. Mediates platelet adhesion to subendothelial collagen through GpIb — hence a platelet-type bleeding pattern
2. Carrier protein for factor VIII, protecting it from degradation — so vWF deficiency also lowers factor VIII and gives a coagulation-type defect
Synthesised by endothelial cells (Weibel–Palade bodies) and megakaryocytes

CLINICAL PEARL

Von Willebrand disease has features of both a platelet and a coagulation disorder, because vWF does two jobs. Loss of adhesion gives mucocutaneous bleeding and a prolonged bleeding time; loss of the factor VIII carrier gives a prolonged aPTT. Recognising the dual role explains every laboratory finding without memorising them.

Classification

Type	Defect	Share	Inheritance
Type 1	Partial quantitative deficiency	About 75% — the commonest; usually mild	Autosomal dominant
Type 2	Qualitative defect (2A, 2B, 2M, 2N)	About 20%	Autosomal dominant (2N recessive)
Type 3	Complete deficiency; severe, resembling haemophilia with haemarthrosis	Rare	Autosomal recessive

Clinical and Laboratory Features

Feature	Finding
Bleeding pattern	Mucocutaneous — epistaxis, gum bleeding, easy bruising, menorrhagia (often the presenting complaint), bleeding after dental extraction
Sex distribution	Both sexes equally — unlike haemophilia
Platelet count	Normal (except type 2B, where it is low)
Bleeding time	Prolonged
APTT	Prolonged or normal, depending on the factor VIII level
VWF antigen and activity (ristocetin cofactor)	Reduced — diagnostic
Factor VIII	Reduced
Ristocetin-induced platelet aggregation	Impaired — and this is the only agent that is abnormal, which is characteristic

Comparison and Applied Aspects

Feature	Haemophilia A	Von willebrand disease
Inheritance	X-linked recessive	Usually autosomal dominant
Sex affected	Males	Both
Bleeding type	Deep — joints and muscles	Mucocutaneous
Bleeding time	Normal	Prolonged
APTT	Prolonged	Prolonged or normal
Factor VIII	Low	Low
VWF	Normal	Low

Desmopressin is the treatment of choice in type 1, releasing stored vWF from endothelial Weibel–Palade bodies; a trial dose confirms responsiveness
It is contraindicated in type 2B, where it releases abnormal vWF that binds platelets and worsens the thrombocytopenia
VWF-containing factor VIII concentrate for type 3 and for non-responders
Tranexamic acid and the combined oral contraceptive are effective for menorrhagia, which is often the dominant problem in women
Levels rise with pregnancy, oestrogen, stress and inflammation, so testing during any of these may give a falsely normal result and should be repeated
Consider it in any woman with lifelong heavy periods and a normal gynaecological examination — it is frequently missed for years

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