Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab

Am J Kidney Dis. 2015 Dec;66(6):1067-70. doi: 10.1053/j.ajkd.2015.06.032. Epub 2015 Sep 26.


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; 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAMTS13 Protein
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Humans
  • Male
  • Purpura, Thrombotic Thrombocytopenic / diagnosis*
  • Purpura, Thrombotic Thrombocytopenic / drug therapy*
  • Purpura, Thrombotic Thrombocytopenic / genetics
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • eculizumab
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human