title: The incidence and treatment of bleeding episodes in non-severe haemophilia A patients with inhibitors.
abstract: The development of an inhibitory antibody in non-severe haemophilia A patients may aggravate the bleeding phenotype considerably. Effective treatment of bleeding episodes may be challenging, with ensuing severe complications. At present, evidence is scarce for optimal treatment of bleeding episodes in this patient group. The aim of this study was to describe the incidence and the treatment of bleeding episodes in inhibitor patients in a population-based unselected cohort of non-severe haemophilia A patients with clinically relevant inhibitors. Data were available for 100 of the 107 non-severe haemophilia A patients (factor VIII (FVIII) baseline, 2-40 IU/dl) from 29 centres in Europe and one centre in Australia who had developed a clinically relevant inhibitor between 1980 and 2011. The majority (89 %) of the patients were treated during the inhibitor period for bleeding episodes or a surgical intervention: 66 % needed treatment for bleeding episodes, at a median annual bleeding rate (ABR) of 1.1 (interquartile range (IQR) 0.1-2.5) and a median total of 2 (IQR 1-6) bleeding episodes. Compared to the median ABR before inhibitor development of 0.095 bleeds per year (IQR 0.02-0.42), the increase in ABR is more than a 10-fold. More than 90 % of the bleeding episodes were treated with only one type of product, most frequently (51 %) FVIII concentrates. This study provides the incidence of bleeding episodes and treatment choices in non-severe haemophilia A patients with inhibitors. The 10-fold increase to a median ABR of 1.1 episodes per year emphasizes the impact of inhibitor development for non-severe haemophilia A patients.
authors.forename: Alice S
authors.initials: AS
authors.lastname: van Velzen
authors.forename: Corien L
authors.initials: CL
authors.lastname: Eckhardt
authors.forename: Nina
authors.initials: N
authors.lastname: Streefkerk
authors.forename: Marjolein
authors.initials: M
authors.lastname: Peters
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Hart
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyak
authors.forename: Robert
authors.initials: R
authors.lastname: Klamroth
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
authors.forename: Marten
authors.initials: M
authors.lastname: Nijziel
authors.forename: Piercarla
authors.initials: P
authors.lastname: Schinco
authors.forename: Thynn T
authors.initials: TT
authors.lastname: Yee
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
authors.affiliation: Karin Fijnvandraat, Department of Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands, Tel.: +31 20 5662727, E-mail: c.j.fijnvandraat@amc.uva.nl.
authors.forename: Karin
authors.initials: K
authors.lastname: Fijnvandraat
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000737:chemistry; D015331:Cohort Studies; D005169:Factor VIII / Q000032:analysis / Q000037:antagonists & inhibitors; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000453:epidemiology*; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D000906:Antibodies; D005169:Factor VIII
keywords: Haemophilia A; bypassing agents; factor VIII inhibitors; haemostasis; management of disease