Key Facts

vWD results from inherited deficiency or dysfunction of von Willebrand factor (vWF), a multimeric glycoprotein essential for platelet adhesion and as a carrier for factor VIII.

Epidemiology

• Most common inherited bleeding disorder: prevalence up to 1% (clinically significant disease ~0.01%)
• Equal sex distribution, but women more symptomatic (menstruation, pregnancy)
• Estimated ~9,000 patients registered with vWD in the UK

Aetiology

• Mutations in the VWF gene (chromosome 12)
• Type 1 (70-80%): partial quantitative deficiency (AD, variable penetrance)
• Type 2 (20%): qualitative defects (2A, 2B, 2M, 2N subtypes)
• Type 3 (<5%): virtually complete deficiency of vWF (AR, most severe)
• Acquired vWD: associated with MPNs, aortic stenosis (Heyde syndrome), hypothyroidism, SLE, lymphoproliferative disorders

Pathophysiology

• vWF has two critical roles:
  1. Platelet adhesion: bridges platelets to exposed subendothelial collagen (via GPIb)
  2. Factor VIII carrier: protects FVIII from degradation (prolongs FVIII half-life)
• Deficiency/dysfunction → impaired primary haemostasis (mucocutaneous bleeding)
• In severe disease (Type 3), FVIII levels also very low → secondary haemostasis defects (haemophilia-like bleeding)

Type 1 (Mild-Moderate)

• Epistaxis (most common symptom in children)
• Easy bruising
• Menorrhagia (most common symptom in women)
• Prolonged bleeding after dental extraction or surgery
• Post-partum haemorrhage

Type 2

• Similar to Type 1 but may be more severe depending on subtype
• Type 2B: may have mild thrombocytopenia (abnormal vWF binds platelets spontaneously)

Type 3 (Severe)

• Mucocutaneous bleeding (as above, but more severe)
• Haemarthroses and muscle haematomas (due to very low FVIII – resembles haemophilia)
• GI bleeding

Red Flags

• Unexplained menorrhagia in young women → consider vWD
• Recurrent post-surgical bleeding with normal platelet count and coagulation → investigate vWD
• Family history of bleeding with autosomal inheritance pattern

Bedside

• Bleeding assessment tool (BAT/ISTH-BAT): standardised bleeding score
• Examination for bruising, petechiae

Bloods

• FBC: platelet count (usually normal; may be low in Type 2B)
• Coagulation screen: APTT may be prolonged (due to low FVIII); PT and fibrinogen normal
• vWF:Ag (antigen): quantitative vWF level
• vWF:RCo (ristocetin cofactor activity) or vWF:GPIbM: functional vWF activity
• Factor VIII:C: often low (proportional to vWF deficiency)
• vWF:RCo/vWF:Ag ratio: <0.7 suggests Type 2 (qualitative defect)

Special Tests

• vWF multimer analysis: distinguishes Type 2 subtypes (loss of high MW multimers in 2A)
• RIPA (ristocetin-induced platelet aggregation): increased at low-dose ristocetin in Type 2B
• DDAVP trial: test response before relying on it therapeutically
• Genetic testing: available for Type 2 and Type 3, family studies
• Blood group: Type O individuals have ~25% lower vWF levels (important for interpretation)

Imaging

• Not routinely required

Non-pharmacological

• Avoid aspirin and NSAIDs (impair platelet function)
• Patient education: medical alert bracelet, treatment plan
• Genetic counselling for family members
• Pre-operative planning: liaise with haemophilia centre

Pharmacological

Desmopressin (DDAVP) – first-line for Type 1 and some Type 2A/2M:

• 0.3mcg/kg IV over 30 minutes; or intranasal 150-300mcg
• Releases stored vWF from Weibel-Palade bodies
• Raises vWF and FVIII levels 3-5 fold within 30-60 minutes
• Tachyphylaxis occurs after repeated doses (limit to 3-4 doses)
• Avoid in Type 2B (may worsen thrombocytopenia)
• Monitor for hyponatraemia (antidiuretic effect)

vWF-containing concentrate (Haemate P, Wilate):

• For Type 3, severe Type 2, DDAVP non-responders, or major surgery
• Haemate P 40-60 IU/kg then 20-40 IU/kg every 12-24h
• Dose guided by vWF:RCo and FVIII targets

Adjunctive:

• Tranexamic acid 1g TDS PO – first-line adjunct for mucosal bleeding and menorrhagia
• Combined oral contraceptive pill or levonorgestrel IUS for menorrhagia

Referral Criteria

• All suspected vWD → haemophilia centre
• Pre-operative assessment for known vWD → haematology liaison
• Pregnancy planning → specialist obstetric haematology care

• Type 1: generally mild disease; normal life expectancy with appropriate management
• Type 2: variable severity depending on subtype
• Type 3: significant bleeding risk; requires regular vWF/FVIII replacement
• Pregnancy: vWF levels rise in pregnancy (may normalise in Type 1); post-partum haemorrhage risk remains elevated (levels fall rapidly after delivery)
• Quality of life significantly impacted by menorrhagia and recurrent bleeding in severe disease

vWD Classification Summary

Treatment Selection