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.
Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab / C. Pecoraro, A.V.S. Ferretti, E. Rurali, M. Galbusera, M. Noris, G. Remuzzi. - In: AMERICAN JOURNAL OF KIDNEY DISEASES. - ISSN 0272-6386. - 66:6(2015 Dec), pp. 1067-1070.
|Titolo:||Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab|
REMUZZI, GIUSEPPE (Ultimo)
|Parole Chiave:||ADAMTS13; Atypical hemolytic uremic syndrome (aHUS); Complement; Congenital TTP; Eculizumab; Terminal complement pathway; Thrombotic microangiopathy (TMA); Thrombotic thrombocytopenic purpura (TTP); Ultralarge vWF (ULvWF); Von Willebrand factor (vWF) protease; Nephrology|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||dic-2015|
|Data ahead of print / Data di stampa:||22-set-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1053/j.ajkd.2015.06.032|
|Appare nelle tipologie:||01 - Articolo su periodico|