Treatment of congenital thrombotic thrombocytopenic purpura with eculizumab

Carmine Pecoraro, Alfonso Vincenzo Salvatore Ferretti, Erica Rurali, Miriam Galbusera, Marina Noris, Giuseppe Remuzzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1067-1070
Number of pages4
JournalAmerican Journal of Kidney Diseases
Volume66
Issue number6
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Thrombotic Thrombocytopenic Purpura
Complement Activation
Shiga Toxins
Genes
Shiga-Toxigenic Escherichia coli
Complement Membrane Attack Complex
Complement Factor H
Mutation
Hemolytic Anemia
von Willebrand Factor
Acute Kidney Injury
Thrombocytopenia
Diarrhea
Seizures
Peptide Hydrolases
Therapeutics
Endothelial Cells
Monoclonal Antibodies
Kidney
Antibodies

Keywords

  • 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

ASJC Scopus subject areas

  • Nephrology

Cite this

Treatment of congenital thrombotic thrombocytopenic purpura with eculizumab. / Pecoraro, Carmine; Ferretti, Alfonso Vincenzo Salvatore; Rurali, Erica; Galbusera, Miriam; Noris, Marina; Remuzzi, Giuseppe.

In: American Journal of Kidney Diseases, Vol. 66, No. 6, 01.12.2015, p. 1067-1070.

Research output: Contribution to journalArticle

@article{e1b612d717e041c888206407f9273b8c,
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.",
keywords = "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",
author = "Carmine Pecoraro and Ferretti, {Alfonso Vincenzo Salvatore} and Erica Rurali and Miriam Galbusera and Marina Noris and Giuseppe Remuzzi",
year = "2015",
month = "12",
day = "1",
doi = "10.1053/j.ajkd.2015.06.032",
language = "English",
volume = "66",
pages = "1067--1070",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Treatment of congenital thrombotic thrombocytopenic purpura with eculizumab

AU - Pecoraro, Carmine

AU - Ferretti, Alfonso Vincenzo Salvatore

AU - Rurali, Erica

AU - Galbusera, Miriam

AU - Noris, Marina

AU - Remuzzi, Giuseppe

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - ADAMTS13

KW - atypical hemolytic uremic syndrome (aHUS)

KW - complement

KW - congenital TTP

KW - eculizumab

KW - terminal complement pathway

KW - thrombotic microangiopathy (TMA)

KW - Thrombotic thrombocytopenic purpura (TTP)

KW - ultralarge vWF (ULvWF)

KW - von Willebrand factor (vWF) protease

UR - http://www.scopus.com/inward/record.url?scp=84948085489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948085489&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2015.06.032

DO - 10.1053/j.ajkd.2015.06.032

M3 - Article

C2 - 26409664

AN - SCOPUS:84948085489

VL - 66

SP - 1067

EP - 1070

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 6

ER -