Curriculum · Hematology
Von Willebrand disease
What it is, and how it is inherited
Von Willebrand disease is the most common inherited bleeding disorder, with a prevalence of 1%, and it is usually autosomal dominant. VWF levels vary according to blood group: non-group O patients have higher levels than group O patients.
Von Willebrand factor is a glycoprotein. It is the carrier protein for FVIII, preventing its proteolytic degradation in plasma, and it is an adhesive protein involved in the interaction between platelets and the blood vessel wall. Those two roles carry the whole disease: without the factor the platelets do not adhere, and FVIII falls with it.
The inheritance is dominant with one exception. Type 1 is autosomal dominant; type 2 is autosomal dominant except 2N, which is recessive; type 3 is autosomal recessive.
The three types
- Type 1: quantitative defect, a decreased amount of VWF with a proportional decrease in VWF activity. 80% of cases, mild bleeding. A second page gives it as most common at around 75-80%.
- Type 2: qualitative defect, VWF activity disproportionally lower than quantity. 20% of cases, moderate bleeding, and it has subtypes 2A, 2B, 2M and 2N. A second page gives it as less common at around 15-20%.
- Type 3: severe total quantitative defect, with virtually no VWF produced. 1 per million, autosomal recessive, severe bleeding. A second page gives it as very rare at around under 5%.
The comparison table adds what the platelet count does, which is normal in type 1 and in type 3, and low in type 2B because the VWF binds platelets abnormally, which leads to clearance; and what the multimers do, normal in type 1, absent in type 3, and abnormal in type 2 depending on subtype, with a loss of large multimers in 2A.