von Willebrand Disease
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Direct answer
Menorrhagia since menarche, dental extraction ooze and easy bruising with a normal platelet count and a variably prolonged APTT — that constellation makes von Willebrand disease the commonest inherited bleeding disorder, with type 1 accounting for about three-quarters. Diagnosis rests on a panel read intelligently: von Willebrand factor antigen, its activity (ristocetin cofactor or GPIbM-based), factor VIII and, when needed, multimers — interpreted against blood group, because group O alone lowers the level by a quarter to a third. Most patients respond to desmopressin; type 3 and non-responders need plasma-derived, factor-VIII-containing von Willebrand concentrate, and type 2B is the subtype in which desmopressin actively harms.
What you must remember
- Von Willebrand factor has two jobs — platelet adhesion through GPIb and factor VIII carriage — hence a platelet-type bleeding history sits alongside a prolonged APTT with low factor VIII.
- Type 1 (about 75%, autosomal dominant, partial deficiency) and type 3 (autosomal recessive, virtually absent factor with factor VIII under 1 IU/dL and haemophilia-severe bleeding) are quantitative; type 2 subtypes are qualitative.
- Type 2 subtypes: 2A loses high-molecular-weight multimers; 2B binds platelets too avidly, causing thrombocytopenia that worsens after desmopressin; 2M has low function with normal multimers; 2N cannot carry factor VIII and mimics mild haemophilia A in both sexes.
- An activity-to-antigen ratio below about 0.6 separates type 2 from type 1; multimer analysis then resolves 2A, 2B and 2M.
- Diagnostic thresholds: repeated levels below 30 IU/dL support disease; 30-50 IU/dL is "low von Willebrand factor", managed on the bleeding phenotype.
- Desmopressin 0.3 μg/kg after a documented test dose; hyponatraemia is the harm, so restrict fluids for 24 hours, and tachyphylaxis limits repeated dosing to 24-48 hours apart.
- Pregnancy raises the factor two- to three-fold by term, masking type 1 — while type 2B may first appear as new "ITP", and levels fall abruptly postpartum, stacking the risk of secondary postpartum haemorrhage.
- Acquired von Willebrand disease: aortic stenosis with gastrointestinal angiodysplasia (Heyde syndrome), lymphoproliferative disorders, hypothyroidism, myeloma and Wilms tumour in children.
Reading the panel on real patients
A 26-year-old with menorrhagia, haemoglobin 9, APTT mildly prolonged and platelets 280 has antigen 22 IU/dL, activity 20 and factor VIII 28 — ratio near 0.9, everything low together: type 1. A desmopressin test dose lifting activity above 50 IU/dL predicts safe cover for her dental extraction, with tranexamic acid and hormonal control of the menorrhagia alongside. Contrast a second patient: antigen 35, activity 12 — ratio 0.34 — and platelets 90. The low ratio declares type 2, and the thrombocytopenia convicts type 2B, where desmopressin would strip platelets further; she receives a von Willebrand-containing concentrate for procedures instead. Every panel is repeated when the patient is well and unstressed, because illness, exercise and the post-acute phase all perturb levels — a single normal value during an acute episode excludes nothing.
How the exam frames it
The classic stem is the child with recurrent bruising and platelets of 80, labelled immune thrombocytopenia and given steroids that do nothing: a von Willebrand panel with a low activity-to-antigen ratio and thrombocytopenia that worsens on desmopressin unmasks type 2B. The second favourite is the "girl with low factor VIII" — if antigen is normal but factor VIII sits at 10-20% and her father is similarly affected, the answer is type 2N, not a haemophilia carrier, because 2N is autosomal. The third is interpretation discipline: blood group O, recent exercise, stress, pregnancy and oestrogen all shift levels, so the diagnosis demands consistently low values on repeat testing rather than one isolated number.
Frequently asked questions
Which subtype of von Willebrand disease worsens with desmopressin?
Type 2B. Its gain-of-function factor binds platelets more avidly as levels rise, deepening the thrombocytopenia — concentrate therapy is used instead.
Why is the APTT prolonged in von Willebrand disease?
Von Willebrand factor carries factor VIII in the circulation; when it is absent or defective, factor VIII falls and the APTT lengthens. The prothrombin time stays normal.
Which test separates type 1 from type 2?
The activity-to-antigen ratio: below about 0.6 indicates qualitative type 2 disease; in type 1 antigen and activity fall together. Multimer analysis subclassifies the type 2 variants.
Which subtype mimics mild haemophilia A?
Type 2N, the factor VIII-binding defect. Normal antigen with low factor VIII in an autosomal (father-to-child) pattern distinguishes it from X-linked haemophilia carriage.
What is the treatment for type 3 disease?
Plasma-derived von Willebrand factor concentrate containing factor VIII, given for prophylaxis or bleeding; desmopressin is useless when the factor is virtually absent.
What is Heyde syndrome?
Aortic stenosis with acquired type 2A-like von Willebrand disease and bleeding from gastrointestinal angiodysplasia — high shear strips the high-molecular-weight multimers. Valve replacement corrects it.