Molecular mechanisms in thrombotic thrombocytopenic purpura.

Abstract

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.

• Authors: Han-Mou Tsai
• Journal: Seminars in thrombosis and hemostasis (Semin Thromb Hemost) Vol. 30 Issue 5 Pg. 549-57 (Oct 2004) ISSN: 0094-6176 [Print] United States
• PMID: 15497097 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

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

Topics

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