Blood Journal
Leading the way in experimental and clinical research in hematology

Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria

  1. Peter Hillmen1,
  2. Petra Muus2,
  3. Ulrich Dührsen3,
  4. Antonio M. Risitano4,
  5. Jörg Schubert5,
  6. Lucio Luzzatto6,
  7. Hubert Schrezenmeier7,
  8. Jeffrey Szer8,
  9. Robert A. Brodsky9,
  10. Anita Hill1,
  11. Gerard Socié10,
  12. Monica Bessler11,
  13. Scott A. Rollins12,
  14. Leonard Bell12,
  15. Russell P. Rother12, and
  16. Neal S. Young13
  1. 1Leeds General Infirmary, Leeds, United Kingdom;
  2. 2Radboud University Medical Center, Nijmegen, The Netherlands;
  3. 3University Essen, Essen, Germany;
  4. 4Federico II University, Naples, Italy;
  5. 5Saarland University Medical School, Homburg-Saarland, Germany;
  6. 6Istituto Toscano Tumori, Florence, Italy;
  7. 7Institute of Transfusion Medicine, University Hospital, Ulm, Germany;
  8. 8Royal Melbourne Hospital, Melbourne, Australia;
  9. 9Johns Hopkins School of Medicine, Baltimore, MD;
  10. 10Hôpital Saint-Louis and Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France;
  11. 11Washington University, St Louis, MO;
  12. 12Alexion Pharmaceuticals, Cheshire, CT; and
  13. 13National Heart, Lung, and Blood Institute, Bethesda, MD


Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TE in patients with PNH. Clinical trial participants included all patients in the 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P < .001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before eculizumab to 3 events during eculizumab (P < .001). The TE event rate in antithrombotic-treated patients (n = 103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizumab treatment (P < .001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at (study ID no. NCT00122317).

  • Submitted June 13, 2007.
  • Accepted August 9, 2007.
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