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Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Loomans, JI
  • van Velzen, AS
  • Eckhardt, CL
  • Peters, M
  • Mäkipernaa A
  • Holmstrom, M
  • Brons, PP
  • Dors, N
  • Voorberg, J
  • van der Bom, JG
  • Fijnvandraat, K

Grupos

Abstract

Background: The bleeding phenotype in patients with mild/moderate hemophilia A (MHA) is inversely associated with the residual plasma concentration of factor VIII (FVIII:C). Within a group of patients with the same F8 missense mutation, baseline FVIII: C may vary, because, in healthy individuals, von Willebrand factor (VWF) levels, ABO blood group and age are also known to influence baseline FVIII: C. Our understanding of the pathophysiologic process of the causative genetic event leading to reduced baseline FVIII: C in MHA patients is still limited. Objectives: To estimate the variation and determinants of baseline FVIII:C among MHA patients with the same F8 missense mutation. Methods: Three hundred and forty-six patients carrying mutations that were present in at least 10 patients in the cohort were selected from the INSIGHT and the RISE studies, which are cohort studies including data of 3534 MHA patients from Europe, Canada, and Australia. Baseline FVIII: C was measured with a one-stage clotting assay. We used Levene's test, univariate and multivariate linear regression, and mixed-model analyses. Results: For 59% of patients, the observed variation in baseline FVIII: C was explained by age and genotype. Compared to FVIII: C in patients with Arg612Cys, FVIII: C was significantly different in patients with eight other F8 missense mutations. Intra-individual variation explained 45% of the observed variance in baseline FVIII: C among patients with the same mutation. Conclusion: Our results indicate that baseline FVIII: C levels are not exclusively determined by F8 genotype in MHA patients. Insights into other factors may provide potential novel targets for the treatment of MHA.

Datos de la publicación

ISSN/ISSNe:
1538-7933, 1538-7836

JOURNAL OF THROMBOSIS AND HAEMOSTASIS  WILEY-BLACKWELL

Tipo:
Article
Páginas:
246-254
PubMed:
27943580
Factor de Impacto:
2,353 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 28

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Keywords

  • cohort study; determinants; FVIII; hemophilia A; mutation

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