Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response

Alessandro Gringeri, R. Musso, M. G. Mazzucconi, G. Piseddu, M. Schiavoni, P. Pignoloni, P. M. Mannucci, S. Bernasconi, D. Brito, G. Castaman, A. Coppola, G. Di Minno, G. Gamba, P. G. Iannaccaro, R. Landolfi, M. Muça Perja, M. Prieto, E. Santagostino, P. C. Schinco, A. Villar

Research output: Contribution to journalArticle

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Abstract

Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/ factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure. Patients with severe or moderate haemophilia A and high responding inhibitors who had at least one poor prognostic factor for ITI failure were prospectively followed-up. Success was defined by undetectable inhibitor, recovery and half life >66% of expected values. ITI dose regimens were chosen by each haemophilia centre. Seventeen haemophiliacs (16 severe, one moderate), aged 4-54 years (median 23) were followed-up for 6-71 months. Poor prognostic factors were delayed-onset ITI (n = 16), age >6 years (n = 16), previously failed ITI (n = 4), inhibitor peak >200 BU (n = 2) and inhibitor >10 BU when ITI was started (n = 4). Complete success was obtained in nine patients (53%) after 4-30 months of treatment (median 24), including two of four patients who had previously failed ITI. Seven patients achieved a partial success, with sustained low inhibitor titres (median 1.5 BU, range 1.1-2.8) but abnormal recovery and/or half-life, while the remaining patient withdrew ITI after 12 months when the inhibitor titer was still 70 BU. These findings suggest that high purity VWF/FVIII complex concentrates are effective in ITI, even in patients at high risk of failure.

Original languageEnglish
Pages (from-to)373-379
Number of pages7
JournalHaemophilia
Volume13
Issue number4
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Immune Tolerance
Factor VIII
Hemophilia A
von Willebrand Factor
Half-Life

Keywords

  • Haemophilia A
  • Immune tolerance
  • Inhibitors
  • Rescue treatment
  • VWF

ASJC Scopus subject areas

  • Hematology

Cite this

Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. / Gringeri, Alessandro; Musso, R.; Mazzucconi, M. G.; Piseddu, G.; Schiavoni, M.; Pignoloni, P.; Mannucci, P. M.; Bernasconi, S.; Brito, D.; Castaman, G.; Coppola, A.; Di Minno, G.; Gamba, G.; Iannaccaro, P. G.; Landolfi, R.; Perja, M. Muça; Prieto, M.; Santagostino, E.; Schinco, P. C.; Villar, A.

In: Haemophilia, Vol. 13, No. 4, 07.2007, p. 373-379.

Research output: Contribution to journalArticle

Gringeri, A, Musso, R, Mazzucconi, MG, Piseddu, G, Schiavoni, M, Pignoloni, P, Mannucci, PM, Bernasconi, S, Brito, D, Castaman, G, Coppola, A, Di Minno, G, Gamba, G, Iannaccaro, PG, Landolfi, R, Perja, MM, Prieto, M, Santagostino, E, Schinco, PC & Villar, A 2007, 'Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response', Haemophilia, vol. 13, no. 4, pp. 373-379. https://doi.org/10.1111/j.1365-2516.2007.01484.x
Gringeri, Alessandro ; Musso, R. ; Mazzucconi, M. G. ; Piseddu, G. ; Schiavoni, M. ; Pignoloni, P. ; Mannucci, P. M. ; Bernasconi, S. ; Brito, D. ; Castaman, G. ; Coppola, A. ; Di Minno, G. ; Gamba, G. ; Iannaccaro, P. G. ; Landolfi, R. ; Perja, M. Muça ; Prieto, M. ; Santagostino, E. ; Schinco, P. C. ; Villar, A. / Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. In: Haemophilia. 2007 ; Vol. 13, No. 4. pp. 373-379.
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