Inhibitor development and mortality in non-severe hemophilia A

C. L. Eckhardt, J. I. Loomans, A. S. van Velzen, M. Peters, E. P. Mauser-Bunschoten, R. Schwaab, M. G. Mazzucconi, A. Tagliaferri, B. Siegmund, S. E. Reitter-Pfoertner, J. G. van der Bom, K. Fijnvandraat, K. Fijnvandraat, M. Peters, P. W. Kamphuisen, J. G. van der Bom, K. Peerlinck, J. Oldenburg, E. Santagostino, J. AstermarkC. L. Eckhardt, A. S. van Velzen, N. Streefkerk, J. L. Loomans, A. van Eijkelenburg, A. J. Jansen, C. C. Kruijt, B. van Tienoven, A. C G van Baar, I. W. Corten, K. Meijer, M. R. Nijziel, N. Dors, K. Hamulyak, E. Beckers, P. P. Brons, B. A P Laros-van Gorkom, W. L. van Heerde, F. Leebeek, M. Kruip, M. H. Cnossen, E. Mauser-Bunschoten, K. Fischer, F. J. Smiers, C. Hermans, R. Schwaab, B. Siegmund, R. Klamroth, C. Escuriola-Ettingshausen, C. Königs, P. Petrini, M. Holmström, A. Mäkipernaa, C. Male, I. Pabinger, S. E. Reitter-Pfoertner, R. D. Keenan, R. Liesner, K. Khair, T. T. Yee, D. P. Hart, S. Rangarajan, M. Mitchell, G. Thompson, S. Haya, A. Moret, A. R. Cid, V. Jimenez-Yuste, M. E. Mancuso, M. G. Mazzuconni, C. Santoro, M. Morfini, G. Castaman, P. Schinco, A. Tagliaferri, G. F. Rivolta, H. Platokouki, S. McRae

Research output: Contribution to journalArticlepeer-review


Background: The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. Objectives: We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. Methods: In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. Results: During 64200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71years (IQR, 60-81). In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was >5 times increased compared with that for those without inhibitors (age-adjusted mortality rate ratio, 5.6). Conclusion: Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients.

Original languageEnglish
Pages (from-to)1217-1225
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - Jul 1 2015


  • Cause of death
  • Hemophilia A
  • Hemorrhage
  • Mortality
  • Neutralizing antibodies

ASJC Scopus subject areas

  • Hematology


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