Molecular mechanisms in thrombotic thrombocytopenic purpura

Semin Thromb Hemost. 2004 Oct;30(5):549-57. doi: 10.1055/s-2004-835675.


Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolysis. Unlike the typical hemolytic uremic syndrome (HUS), which follows infection with shiga toxin-producing microorganisms, most cases of TTP do not have an obvious etiology. Recent studies revealed that a plasma zinc metalloprotease ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motif) 13 cleaves von Willebrand factor in a shear-dependent manner. Deficiency of ADAMTS13, due to autoimmune inhibitors of the protease or genetic mutation in the ADAMTS13 gene, results in a propensity to the development of von Willebrand factor-platelet aggregation and intravascular thrombosis characteristic of TTP. The identification of the molecular defect in TTP raises the prospect that this hitherto mysterious disorder will be managed with a more rationally designed strategy in the near future.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ADAM Proteins
  • ADAMTS13 Protein
  • Blood Platelets / cytology
  • Cloning, Molecular
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / diagnosis
  • Hemolytic-Uremic Syndrome / genetics
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / physiology
  • Mutation
  • Purpura, Thrombotic Thrombocytopenic / blood
  • Purpura, Thrombotic Thrombocytopenic / diagnosis*
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • von Willebrand Factor / metabolism
  • von Willebrand Factor / physiology


  • von Willebrand Factor
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAMTS13 Protein
  • ADAMTS13 protein, human