title: Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab.
abstract: A 12-year-old boy was hospitalized for hemolytic anemia, thrombocytopenia, acute kidney injury, and generalized seizures. The childhood onset, severely decreased kidney function, absence of prodromal diarrhea, negative test results for Shiga-like toxin-producing Escherichia coli, elevated plasma levels of the terminal complement complex sC5b-9, and ex vivo testing in endothelial cells showing serum-induced complement activation were all consistent with a diagnosis of complement-mediated atypical hemolytic uremic syndrome. Before plasma ADAMTS13 (von Willebrand factor protease) activity results were available, the patient was treated with the anti-C5 monoclonal antibody eculizumab, and treatment was followed by prompt disease remission. However, results of ADAMT13 activity level tests and gene screening revealed a severe deficiency associated with 2 heterozygous mutations in the ADAMTS13 gene, fully consistent with a diagnosis of congenital thrombotic thrombocytopenic purpura. Screening for atypical hemolytic uremic syndrome-associated genes failed to show a mutation and an assay for plasma anti-factor H antibodies gave negative results both before and after eculizumab treatment initiation. The patient's clinical evolution suggests that complement activation plays a role in the pathogenesis of thrombotic thrombocytopenic purpura and provides unexpected new insights into the treatment of this life-threatening disease.
authors.affiliation: Paediatric Nephrology Unit, Santobono-Pausilipon Hospital, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Pecoraro
authors.affiliation: Paediatric Nephrology Unit, Santobono-Pausilipon Hospital, Naples, Italy.
authors.forename: Alfonso Vincenzo Salvatore
authors.initials: AV
authors.lastname: Ferretti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", Ranica, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Rurali
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", Ranica, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Galbusera
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", Ranica, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", Ranica, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: giuseppe.remuzzi@marionegri.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071120:ADAMTS13 Protein; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D008297:Male; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Thrombotic thrombocytopenic purpura (TTP); atypical hemolytic uremic syndrome (aHUS); complement; congenital TTP; eculizumab; terminal complement pathway; thrombotic microangiopathy (TMA); ultralarge vWF (ULvWF); von Willebrand factor (vWF) protease