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GI Bleeding – David Green, MD, PhD
Northwestern University, Feinberg School of Medicine, Chicago, IL
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.
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von Willebrand's disease: Classification
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| Type 1 |
- Autosomal dominant
- Quantitative deficiency of von Willebrand factor
- Failure of export from storage organelles
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| Type 2 |
- Usually occurs as an autosomal dominant disorder with abnormalities in von Willebrand factor function.
- Gene with point mutations, insertions, and missense mutations.
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| Type 2A |
- Characterized by absence of the higher molecular weight multimers of von Willebrand factor.
- Impaired multimerization.
- Increased proteolysis
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| 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.
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| Type 2-M |
- Decreased binding to subendothelial connective tissue.
- Reduced binding of von Willebrand factor to GPIb-IX-V.
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| 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 either requires demonstrating the lack of binding of von Willebrand factor to factor VIII or genetic analysis.
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| 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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