Thrombotic thrombocytopenic purpura: survival by "giving a dam".
A teenager died suddenly in 1923 of systemic microvascular thrombosis. Dr. Eli Moschcowitz attributed the "hitherto undescribed disease" (now "thrombotic thrombocytopenic purpura," or "TTP") to "some powerful poison" with "both agglutinative and hemolytic properties." In 1982, TTP was found to be a defect in the "processing" of unusually large (UL) von Willebrand factor (VWF) multimers. By 1998, the cause of TTP was known to be either familial absence or acquired inhibition (by autoantibody) of plasma VWF-cleaving metalloprotease. This enzyme, the 13th member of a disintegrin and metalloprotease family with thrombospondin domains (ADAMTS-13), circulates in normal plasma waiting to cleave the long strings of ULVWF multimers emerging from stimulated endothelial cells. Uncleaved ULVWF multimers in TTP induce platelet adhesion and aggregation in the rapidly flowing blood of microvessels. Episodes of TTP are treated by "giving A DAM" (TS-13, that is) contained in normal plasma, either by infusion alone or in combination with plasmapheresis.
Moake
Joel L
JL
Medical Hematology Section The Methodist Hospital, Houston, Texas 77030, USA. jmoake@rice.edu
D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D000071120:ADAMTS13 Protein; D049673:History, 20th Century; D006801:Humans; D008958:Models, Molecular; D010956:Plasmapheresis; D020836:Protein Structure, Quaternary; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology / Q000266:history / Q000628:therapy*; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human