Genetics of type 2B von Willebrand disease: "true 2B," "tricky 2B," or "not 2B." What are the modifiers of the phenotype?

Semin Thromb Hemost. 2008 Sep;34(6):520-31. doi: 10.1055/s-0028-1103363. Epub 2008 Nov 28.

Abstract

Type 2B von Willebrand disease (VWD) is a qualitative type of VWD with a unique feature among VWD types, resulting from an increased binding of von Willebrand factor (VWF) to its platelet receptor glycoprotein 1b-alpha (GP1BA). This heightened responsiveness takes place in vivo without endothelial injury or shear stress induction, typically resulting in loss of the hemostatically most active high-molecular-weight VWF multimers and leading to a bleeding diathesis. This process also typically leads to clearance of platelets and thus usually mild thrombocytopenia. At least this describes the classic representation of type 2B VWD (i.e., the typical picture we have come to know since the description/classification of this disorder in the early 1990s). Over more recent years, several reports have described individual cases, groups of patients, and families diagnosed with type 2B VWD where this picture was not typical in one or more aspects. This review discusses type 2B-like disorders and sheds light on potential phenotypic modifiers that might be responsible for the variation encountered with the classic picture of type 2B VWD as well as the impact on the diagnostic certainty of type 2B VWD.

Publication types

  • Review

MeSH terms

  • ADAM Proteins / metabolism
  • ADAMTS13 Protein
  • Bleeding Time
  • Humans
  • Membrane Glycoproteins
  • Membrane Proteins / metabolism*
  • Mutation
  • Phenotype
  • Platelet Aggregation / drug effects
  • Platelet Function Tests
  • Platelet Glycoprotein GPIb-IX Complex
  • Polymorphism, Genetic
  • Ristocetin
  • von Willebrand Diseases / classification
  • von Willebrand Diseases / diagnosis*
  • von Willebrand Diseases / genetics*
  • von Willebrand Factor / genetics*

Substances

  • Membrane Glycoproteins
  • Membrane Proteins
  • Platelet Glycoprotein GPIb-IX Complex
  • adhesion receptor
  • von Willebrand Factor
  • Ristocetin
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human