Molecular mechanisms in thrombotic thrombocytopenic purpura.
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.
Tsai
Han-Mou
HM
Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA. htsai@montefiore.org
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D001792:Blood Platelets / Q000166:cytology; D003001:Cloning, Molecular; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology
D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human