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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Commonest inherited bleeding disorder — affects up to 1% of the population. Autosomal dominant (types 1 and 2), autosomal recessive (type 3)
- VWF functions: (1) mediates platelet adhesion to damaged endothelium, (2) carries and protects factor VIII in plasma
- Clinical pattern: mucocutaneous bleeding (menorrhagia, epistaxis, gum bleeding, post-surgical bleeding) — similar to platelet disorders, unlike haemophilia
- Lab: prolonged APTT (due to low factor VIII), ± prolonged PFA-100. Diagnose with VWF antigen, VWF activity (ristocetin cofactor), factor VIII level
- Treatment: DDAVP (releases stored VWF — works well for type 1) for minor bleeding/procedures. VWF-containing factor concentrate for severe bleeding or type 3
Overview
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by quantitative or qualitative deficiency of von Willebrand factor (VWF). VWF is a large glycoprotein produced by endothelial cells and megakaryocytes that plays two critical roles in haemostasis: mediating platelet adhesion to damaged vessel walls (primary haemostasis) and binding/stabilising factor VIII in the circulation (secondary haemostasis). There are three main types: Type 1 (partial quantitative deficiency, ~70-80%), Type 2 (qualitative dysfunction, ~20%), and Type 3 (virtually complete deficiency, <5% — very rare and severe).
Epidemiology
VWD affects up to 1% of the population (based on laboratory testing), though clinically significant disease is much less common (~1 in 1,000). Types 1 and 2 are autosomal dominant. Type 3 is autosomal recessive. Unlike haemophilia, VWD affects males and females equally. Menorrhagia is often the presenting symptom in women — VWD should be considered in any woman with unexplained heavy menstrual bleeding.
Clinical Features
Symptoms
Menorrhagia — the most common symptom in women, may be the only presentation
Epistaxis — recurrent and often prolonged
Easy bruising
Prolonged bleeding after dental extraction or surgery
GI bleeding (particularly in type 2 — angiodysplasia association)
Post-partum haemorrhage
Signs
Bruising (often superficial, mucocutaneous pattern — unlike deep bleeds of haemophilia)
No joint bleeds except in severe type 3 (which mimics haemophilia)
Mucosal bleeding (gingival, nasal)
Investigations
First-line
APTTMay be prolonged (due to low factor VIII carried by VWF) or NORMAL in mild disease
PTNORMAL (extrinsic pathway unaffected)
Platelet countNORMAL (except type 2B where mild thrombocytopenia may occur due to increased platelet binding)
Second-line
VWF antigen (VWF:Ag)Quantitative measure of VWF protein. Low in types 1 and 3. May be normal in type 2
VWF activity (ristocetin cofactor, VWF:RCo)Measures VWF function. Low in all types. VWF:RCo/VWF:Ag ratio <0.7 suggests type 2
Factor VIII levelOften low (VWF carries and stabilises factor VIII). Very low in type 3
PFA-100 (platelet function analyser)PROLONGED closure time — screening test for primary haemostasis. More useful than bleeding time
Specialist
VWF multimer analysisDistinguishes type 2 subtypes: type 2A (loss of large multimers), type 2B (gain-of-function — increased platelet binding, test with RIPA), type 2M (decreased platelet-dependent function), type 2N (decreased factor VIII binding)
DDAVP trialTest DDAVP response before clinical use — check VWF level and factor VIII 1 hour post-infusion
Genetic testingVWF gene analysis — for subtyping, genetic counselling, and family screening
1
Minor bleeding or procedures (type 1)
- DDAVP (desmopressin): 0.3 µg/kg IV or 300 µg intranasal — releases stored VWF and factor VIII from endothelial cells
- Response in type 1 is usually excellent — VWF and factor VIII levels rise 3-5 fold within 30-60 minutes
- Tachyphylaxis occurs after repeated doses (stores become depleted) — limit to 2-3 doses
- Side effects: facial flushing, headache, hyponatraemia (fluid restrict). AVOID in children <2 years (seizure risk from hyponatraemia)
2
Severe bleeding or type 3 / DDAVP-unresponsive
- VWF-containing factor VIII concentrate (e.g. Haemate P) — plasma-derived product containing both VWF and factor VIII
- Dose according to VWF activity required for clinical scenario
- Recombinant VWF (vonicog alfa) also available
3
Adjunctive measures
- Tranexamic acid: very effective for mucosal bleeding, dental procedures, menorrhagia
- Combined oral contraceptive pill: for menorrhagia in VWD — raises VWF levels and regulates menses
- Levonorgestrel IUS (Mirena): reduces menstrual blood loss
- Avoid aspirin and NSAIDs
4
Type 2B — special considerations
- DDAVP is CONTRAINDICATED in type 2B — can worsen thrombocytopenia by releasing abnormal VWF that binds platelets excessively
- Use VWF-containing concentrate instead
Complications
- Post-surgical bleeding: The most common clinical presentation — often delayed 5-7 days post-procedure
- Post-partum haemorrhage: VWF levels normally rise in pregnancy (physiological) but fall rapidly post-delivery — PPH risk highest in first 2 weeks
- Iron deficiency anaemia: From chronic mucosal blood loss (menorrhagia, epistaxis)
- Haemarthroses: Only in severe type 3 (factor VIII levels very low, mimicking haemophilia)
UKMLA Exam Tips
- 1VWD is the COMMONEST inherited bleeding disorder — much more common than haemophilia
- 2Autosomal dominant (types 1+2) = affects both sexes equally. Haemophilia = X-linked = males only
- 3Mucocutaneous bleeding (menorrhagia, epistaxis, gum bleeding) = VWD/platelet disorder. Deep bleeds (joints, muscles) = haemophilia
- 4DDAVP is first-line for type 1 VWD and mild haemophilia A. NOT for type 2B (worsens thrombocytopenia) or type 3 (no stored VWF to release)
- 5VWF carries factor VIII — so VWD can cause a prolonged APTT due to low factor VIII
- 6Any woman with unexplained menorrhagia should be considered for VWD screening
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