title: TTP/HUS: observational studies generate hypotheses that lead to randomized controlled trials.
abstract: Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is a disease syndrome, and its history exemplifies how small observational studies lead to hypotheses that spawn randomized control trials (RCTs). Moschowitz's original case report coupled with the case findings of Bukowski and Byrne led to the RCT of Rock and the Canadian Apheresis Group that proved plasma exchange was superior to plasma infusion for the treatment of adults with TTP/HUS. Our single case report of continuous plasma exchange coupled with the observations about the pathogenic role of von Willebrand multimer protease of Tsai and Furlan strengthened by a 25-year observational study of plasma exchange treatment for TTP/HUS has led to a proposal to initiate a new RCT.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada. william.clark@lhsc.on.ca
authors.forename: William F
authors.initials: WF
authors.lastname: Clark
authors.forename: Brian R
authors.initials: BR
authors.lastname: Forzley
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Sontrop
authors.forename: Albert
authors.initials: A
authors.lastname: Kadri
authors.forename: Louise M
authors.initials: LM
authors.lastname: Moist
authors.forename: Rita S
authors.initials: RS
authors.lastname: Suri
authors.forename: Marina I
authors.initials: MI
authors.lastname: Salvadori
authors.forename: Marina S
authors.initials: MS
authors.lastname: Salvadori
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
mesh_terms: D051722:ADAM Proteins / Q000276:immunology; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D019317:Evidence-Based Medicine; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D019370:Observation; D010951:Plasma Exchange; D011247:Pregnancy; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human