Inhibitors in nonsevere haemophilia A: outcome and eradication strategies

Alice S. van Velzen; Corien L. Eckhardt; Daniel P. Hart; Marjolein Peters; Savita Rangarajan; Maria Elisa Mancuso; Frans J. Smiers; Kate Khair; Pia Petrini; Victor Jimenez-Yuste; Charles R. M. Hay; Johanna G. van der Bom; Thynn T. Yee; Karin Fijnvandraat; for the INSIGHT study group

doi:10.1160/TH14-11-0940

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(01): 46-55
DOI: 10.1160/TH14-11-0940

Coagulation and Fibrinolysis

Schattauer GmbH

Inhibitors in nonsevere haemophilia A: outcome and eradication strategies

Alice S. van Velzen

¹Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands

,

Corien L. Eckhardt

¹Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands

²Department of Vascular medicine, Academic Medical Center, Amsterdam, the Netherlands

,

Daniel P. Hart

³Royal London Hospital, Barts and The London School of Medicine and Dentistry, London, UK

,

Marjolein Peters

¹Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands

,

Savita Rangarajan

⁴St. Thomas Hospital, London, UK

,

Maria Elisa Mancuso

⁵Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

,

Frans J. Smiers

⁶Leiden University Medical Center, Leiden, the Netherlands

,

Kate Khair

⁷Great Ormond Street Hospital, London, UK

,

Pia Petrini

⁸Karolinska University Hospital, Stockholm, Sweden

,

Victor Jimenez-Yuste

⁹University Hospital La Paz, Madrid, Spain

,

Charles R. M. Hay

¹⁰Royal Infirmary Hospital, Manchester, UK

,

Johanna G. van der Bom

¹¹Center for Clinical Transfusion Research, Sanquin Research and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

,

Thynn T. Yee

¹Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands

,

Karin Fijnvandraat

¹Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands

,

for the INSIGHT study group

› Author Affiliations

Abstract

Summary

In nonsevere haemophilia A (HA) patients the presence of an inhibitor may exacerbate the bleeding phenotype dramatically. There are very limited data on the optimal therapeutic approach to eradicate inhibitors in these patients. We aimed to describe inhibitor eradication treatment in a large cohort of unselected nonsevere HA patients with inhibitors. We included 101 inhibitor patients from a source population of 2,709 nonsevere HA patients (factor VIII 2–40 IU/dl), treated in Europe and Australia (median age 37 years, interquartile range (IQR) 15–60; median peak titre 7 BU/ml, IQR 2–30). In the majority of the patients (71 %; 72/101) the inhibitor disappeared; either spontaneously (70 %, 51/73) or after eradication treatment (75 %, 21/28). Eradication treatment strategies varied widely, including both immune tolerance induction and immunosuppression. Sustained success (no inhibitor after rechallenge with factor VIII concentrate after inhibitor disappearance) was achieved in 64 % (30/47) of those patients rechallenged with FVIII concentrate. In high-titre inhibitor patients sustained success was associated with eradication treatment (unadjusted relative risk 2.3, 95 % confidence interval 1.3–4.3), compared to no eradication treatment. In conclusion, in nonsevere HA patients most inhibitors disappear spontaneously. However, in 35 % (25/72) of these patients an anamnestic response still can occur when rechallenged, thus disappearance in these patients does not always equal sustained response. Treatment for those requiring eradication has to be decided case by case, as one single approach is unlikely to be appropriate for all.

Study was carried out in: Emma Children’s Hospital, Academic Medical Center, Amsterdam, the Netherlands.

Keywords

Haemophilia A - factor VIII inhibitors - eradication treatment - immune tolerance induction

Full Text

References

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