What are the different types of von Willebrand disease?

Type

Description

1

Partial quantitative VWF deficiency

  • The most common form (50 to 70% of cases)
  • Several subtypes depending on intra-platelet VWF content
  • Difficult to diagnose: overlap between VWF levels in patients and the normal population
  • VWF levels between 10 and 50%
  • Corresponding reduction in VWF antigen (VWF:Ag) and in ristocetin cofactor activity (VWF:RCo)
  • Ratio of VWF:RCo/VWF:Ag > 0.7
  • Dominant transmission with varying expression and penetrance

2

Qualitative VWF deficiency

  • Abnormal interaction between VWF and platelets

2A

Deficient platelet adhesion dependent on VWF associated with selective deficiency of high molecular weight (HMW) multimers

  • Abnormal interaction of VWF with platelets; decreased affinity of VWF for platelets due to absence of high molecular weight and intermediate molecular weight (IMW) multimers
  • Ratio of VWF:RCo/VWF:Ag < 0.7
  • Dominant transmission with varying expression and penetrance

2B

High affinity of VWF for platelet glycoprotein Ib

  • Adsorption of HMW multimers on platelets resulting in fluctuating thrombocytopenia
  • Dominant transmission with varying expression and penetrance

2M

Deficient VWF-dependent platelet adhesion with no selective deficiency in HMW multimers

  • Reduced affinity of VWF for platelets not associated with a multimerisation abnormality
  • Dominant transmission with varying expression and penetrance

2N

Marked deficiency in VWF binding to factor VIII

  • Diagnosis through study of VWF binding to FVIII
  • Normal levels of VWF (VWF:Ag and VWF:RCo)
  • Factor VIII deficit with ratio of FVIII:C/VWF:Ag < 0.5
  • Recessive autosomal transmission

3

Complete quantitative VWF deficiency

  • The rarest form: 1 to 3% of patients
  • Subjects homozygous or composite heterozygous
  • VWF undetectable
  • Extremely low levels of factor VIII (< 10%)
  • Autosomal recessive transmission

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