title: Treatment burden, haemostatic strategies and real world inhibitor screening practice in non-severe haemophilia A.
abstract: Inhibitor formation in non-severe haemophilia A is a life-long risk and associated with morbidity and mortality. There is a paucity of data to understand real-world inhibitor screening practice. We evaluated the treatment burden, haemostatic strategies, F8 genotyping and inhibitor screening practices in non-severe haemophilia A in seven London haemophilia centres. In the 2-year study period, 44% (377/853) patients received at least one haemostatic treatment. Seventy-nine percent of those treated (296/377) received factor VIII (FVIII) concentrate. F8 genotype was known in 88% (331/377) of individuals. Eighteen per cent (58/331) had 'high-risk' F8 genotypes. In patients with 'standard-risk' F8 genotypes treated on-demand with FVIII concentrate, 51·3% episodes (243/474) were screened within 1 year. However, poor screening compliance was observed after 'high-risk' treatment episodes. In patients with 'standard-risk' F8 genotypes, 12·3% (28/227) of treatment episodes were screened in the subsequent 6 weeks after surgery or a bleed requiring ≥5 exposure days. Similarly, in the context of 'high-risk' F8 genotypes after any FVIII exposure, only 13·6% (12/88) of episodes were screened within 6 weeks. Further study is required to assess optimal practice of inhibitor screening in non-severe haemophilia A to inform subsequent clinical decisions and provide more robust prevalence data to further understand the underlying immunological mechanism.
authors.affiliation: The Royal London Hospital Haemophilia Centre, QMUL, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Paul
authors.identifier: http://orcid.org/0000-0002-7808-3462
authors.initials: P
authors.lastname: Batty
authors.affiliation: St George's Healthcare NHS Trust, Haemophilia Centre, London, UK.|The Centre for Haemostasis and Thrombosis, St Thomas' Hospital, London, UK.
authors.forename: Steve K
authors.initials: SK
authors.lastname: Austin
authors.affiliation: Great Ormond Street Haemophilia Centre, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Khair
authors.affiliation: Hammersmith Hospital Haemophilia Centre, London, UK.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Millar
authors.affiliation: The United Kingdom National Haemophilia Database, Manchester, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Palmer
authors.affiliation: The Centre for Haemostasis and Thrombosis, St Thomas' Hospital, London, UK.
authors.forename: Savita
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: The Royal London Hospital Haemophilia Centre, QMUL, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Jan-Phillip
authors.initials: JP
authors.lastname: Stümpel
authors.affiliation: Lewisham Hospital Haemophilia Centre, London, UK.
authors.forename: Murugaiyan
authors.initials: M
authors.lastname: Thanigaikumar
authors.affiliation: Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK.
authors.forename: Thynn T
authors.initials: TT
authors.lastname: Yee
authors.affiliation: The Royal London Hospital Haemophilia Centre, QMUL, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Hart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D006490:Hemostatics; C427184:recombinant factor VIII SQ; C078147:F8 protein, human; D005169:Factor VIII
keywords: audit; haemophilia; inhibitor; non-severe; screening