GI Bleeding

David Green, MD, PhD

Northwestern University, Feinberg School of Medicine, Chicago, IL

This case was reviewed and updated in March 2010 by Dr. Alvin H. Schmaier and members of the Teaching Cases Subcommittee.

Copyright of the American Society of Hematology, 2006. ISSN: 1931-6860.

V. PATHOPHYSIOLOGY

The characteristics of the three main types of von Willebrand disease are summarized in the chart below.

von Willebrand's disease: Classification
Type 1
  • Autosomal dominant
  • Quantitative deficiency of von Willebrand factor
  • Failure of export from storage organelles
Type 2
  • Usually occurs as an autosomal dominant disorder with qualitative abnormalities in von Willebrand factor function.
  • Gene with point mutations, insertions, and missense mutations.
Type 2A
  • Characterized by decreased platelet-dependent von Willebrand factor function with selective deficiency of higher molecular weight multimers.
Type 2B
  • Characterized by absence of the higher molecular weight multimers of von Willebrand factor.
  • Associated with thrombocytopenia due to a gain of function mutation resulting in a von Willebrand factor molecule with higher affinity for the GPIb-IX-V receptor, thus enhancing platelet agglutination.
Type 2-M
  • Decreased platelet-dependent von Willebrand factor function with higher molecular weight multimers present.
  • Reduced binding of von Willebrand factor to GPIb-IX-V.
Type 2-N
  • Rare autosomal recessive disorder arising from a mutation in the factor VIII binding site on the von Willebrand factor molecule.
  • Without the protection provided by von Willebrand factor binding, factor VIII levels fall because of a markedly decreased half life.
  • von Willebrand multimers and antigen and activity levels may be normal.
  • Levels of factor VIII are low enough to make it possible to confuse this with classic hemophilia.
  • Specific diagnosis requires either demonstrating the lack of binding of von Willebrand factor to factor VIII or genetic analysis.
Type 3
  • Autosomal recessive.
  • Patients have a near absence of von Willebrand factor.
  • Due to mutations that result in either a complete absence of the protein or a markedly truncated molecule.
  • The most severe form (very impaired hemostasis).
  • Usually recognized in early childhood.


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