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
1   Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands
,
Corien L. Eckhardt
1   Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands
2   Department of Vascular medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Daniel P. Hart
3   Royal London Hospital, Barts and The London School of Medicine and Dentistry, London, UK
,
Marjolein Peters
1   Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands
,
Savita Rangarajan
4   St. Thomas Hospital, London, UK
,
Maria Elisa Mancuso
5   Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
,
Frans J. Smiers
6   Leiden University Medical Center, Leiden, the Netherlands
,
Kate Khair
7   Great Ormond Street Hospital, London, UK
,
Pia Petrini
8   Karolinska University Hospital, Stockholm, Sweden
,
Victor Jimenez-Yuste
9   University Hospital La Paz, Madrid, Spain
,
Charles R. M. Hay
10   Royal Infirmary Hospital, Manchester, UK
,
Johanna G. van der Bom
11   Center for Clinical Transfusion Research, Sanquin Research and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
,
Thynn T. Yee
1   Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands
,
Karin Fijnvandraat
1   Department of Pediatric Hematology, Emma Children’s Hospital, the Academic Medical Center, Amsterdam, the Netherlands
,
for the INSIGHT study group› Author Affiliations
Further Information

Publication History

Received: 13 November 2014

Accepted after minor revision: 13 February 2015

Publication Date:
22 November 2017 (online)

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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.

* A complete list of the members of the INSIGHT Study Group is found in the Appendix.