Intensive peri-operative use of factor VIII and the Arg593 → Cys mutation are risk factors for inhibitor development in mild/moderate hemophilia A

Autor: Marjolein Peters, Corien L. Eckhardt, Pieter Willem Kamphuisen, L.A. Menke, J.H. Van Der Lee, Karin Fijnvandraat, Ronald B. Geskus, C. H. van Ommen
Přispěvatelé: Other departments, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), General Paediatrics, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Epidemiology and Data Science, Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
arginine
Gene mutation
blood clotting factor 8 concentrate
Severity of Illness Index
Gastroenterology
Risk Factors
hemic and lymphatic diseases
Missense mutation
Longitudinal Studies
gene mutation
cysteine
antibody production
adult
article
longitudinal study
risk assessment
Hematology
Middle Aged
continuous infusion
Thrombosis
priority journal
risk factor
disease severity
mutational analysis
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
drug exposure
Adolescent
perioperative period
Mild/moderate
Hemophilia A
Perioperative Care
Young Adult
Internal medicine
Severity of illness
medicine
Genetics
Humans
Intensive FVIII exposure
controlled study
human
Risk factor
Antibody
Autoantibodies
Retrospective Studies
gene identification
Factor VIII
business.industry
missense mutation
Retrospective cohort study
Perioperative
blood clotting factor 8 antibody
medicine.disease
major clinical study
Surgery
Mutation
business
Complication
genetic predisposition
blood clot lysis
Zdroj: Journal of thrombosis and haemostasis, 7(6), 930-937. Wiley-Blackwell
Journal of Thrombosis and Haemostasis, 7(6), 930-937. Wiley
ISSN: 1538-7933
DOI: 10.1111/j.1538-7836.2009.03357.x
Popis: Background: A severe and challenging complication in the treatment of hemophilia A is the development of inhibiting antibodies (inhibitors) directed towards factor VIII (FVIII). Inhibitors aggravate bleeding complications, disabilities and costs. The etiology of inhibitor development is incompletely understood. Objectives: In a large cohort study in patients with mild/moderate hemophilia A we evaluated the role of genotype and intensive FVIII exposure in inhibitor development. Patients/methods: Longitudinal clinical data from 138 mild/moderate hemophilia A patients were retrospectively collected from 1 January 1980 to 1 January 2008 and analyzed by multivariate analysis using Poisson regression. Results: Genotyping demonstrated the Arg593Cys missense mutation in 52 (38%) patients; the remaining 86 patients had 26 other missense mutations. Sixty-three (46%) patients received intensive FVIII concentrate administration, 41 of them for surgery. Ten patients (7%) developed inhibitors, eight of them carrying the Arg593Cys mutation. Compared with the other patients, those with the Arg593Cys mutation had a 10-fold increased risk of developing inhibitors (RR 10; 95% CI, 0.9-119).The other two inhibitor patients had the newly detected mutations Pro1761Gln and Glu2228Asp. In both these patients and in five patients with genotype Arg593Cys, inhibitors developed after intensive peri-operative use of FVIII concentrate (RR 186; 95% CI, 25-1403). In five of the 10 inhibitor patients FVIII was administered by continuous infusion during surgery (RR 13; 95% CI, 1.9-86). Conclusion: The Arg593Cys genotype and intensive peri-operative use of FVIII, especially when administered by continuous infusion, are associated with an increased risk for inhibitor development in mild/ moderate hemophilia A. © 2009 International Society on Thrombosis and Haemostasis.
Databáze: OpenAIRE
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