Inhibitor development in non-severe haemophilia across Europe

Kathelijn Fischer; Alfonso Iorio; Riitta Lassila; Flora Peyvandi; Gabriele Calizzani; Alex Gatt; Thierry Lambert; Jerzy Windyga; Estelle A. Gilman; Michael Makris; the EUHASS participants; on behalf of

doi:10.1160/TH14-12-1044

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 114(04): 670-675
DOI: 10.1160/TH14-12-1044

Coagulation and Fibrinolysis

Schattauer GmbH

Inhibitor development in non-severe haemophilia across Europe

Kathelijn Fischer

¹Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands

²Van Creveldkliniek, University Medical Centre Utrecht, The Netherlands

,

Alfonso Iorio

³Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Toronto, Canada

⁴Department of Medicine, McMaster University, Hamilton, Canada

,

Riitta Lassila

⁵Department of Hematology, Unit of Coagulation Disorders, Helsinki University Central Hospital, Finland

,

Flora Peyvandi

⁶Angelo Bianchi Bonomi, Hemophilia and Thrombosis centre, IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

⁷Department of pathophysiology and Transplantation, University of Milan, Milan, Italy

,

Gabriele Calizzani

⁸European Haemophilia consortium and Italian National Blood Centre, Rome, Italy

,

Alex Gatt

⁹Mater Dei Hospital, Tal-QRoqq, Msida, Malta

,

Thierry Lambert

¹⁰Hopital Bicetre, Paris, France

,

Jerzy Windyga

¹¹Institute for Hematology and Transfusion Medicine, Warsaw, Poland

,

Estelle A. Gilman

¹²Department of Cardiovascular Science, University of Sheffield, Sheffield, UK

,

Michael Makris

¹²Department of Cardiovascular Science, University of Sheffield, Sheffield, UK

¹³Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK

,

the EUHASS participants

› Institutsangaben

Abstract

Summary

Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95 % confidence intervals (95 % CI) were calculated according to diagnosis and concentrate used. Between 1–10–2008 and 31–12–2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95 % CI 0.30–0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72 % occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001–0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.

Keywords

Factor VIII inhibitors - epidemiological studies - haemophilia A / B - haemophilia therapy - non-severe haemophilia - factor concentrates

Volltext

Referenzen

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