Prevalence, biological phenotype and genotype in moderate/ mild hemophilia A with discrepancy between one-stage and chromogenic factor VIII activity - Archive ouverte HAL Access content directly
Journal Articles Journal of Thrombosis and Haemostasis Year : 2011

Prevalence, biological phenotype and genotype in moderate/ mild hemophilia A with discrepancy between one-stage and chromogenic factor VIII activity

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Abstract

Background: In most laboratories, the severity of hemophilia A is assessed by the factor VIII activity (FVIII:C) one-stage assay. However, comparisons of these results with those of two-stage assays can reveal discrepancies and suggest misdiagnosis. Patients/Methods: In this monocentric study, we measured FVIII:C with two methods (one-stage chronometric and chromogenic assays) in 307 (173 families) patients with moderate/mild hemophilia A. To compare results, we used a chronometric/chromogenic ratio. Discrepancy was defined as a ratio < 0.5 or > 1.5. We studied their putative involvement at known FVIII functional sites, their interspecies conservation status, and their spatial position within the FVIII structure. Results: Thirty-six patients from 17 families exhibited a discrepancy between the two assays: 12 (6.9%) families had a low ratio (< 0.5), and five (2.9%) families had a high ratio (> 1.5). Qualitative deficiency was diagnosed in about 16% of the families. Molecular studies were performed in 15 of these 17 families, resulting in each case in the identification of missense mutations, including three novel mutations. We were further able to propose a pathophysiologic explanation. Conclusions: In this monocentric study, we have demonstrated a discrepancy between FVIII:C assay results in 10% of families with moderate/mild hemophilia A. The prevalence of ÔinverseÕ discrepancy (i.e. low chronometric/chromogenic ratio) is high as compared with previous reports. We suggest that both FVIII:C assays are recommended in patients with moderate/mild hemophilia A for a complete biological phenotype. This could also improve our knowledge of the FVIII structure-function relationships.
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inserm-02441164 , version 1 (15-01-2020)

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Marc Trossaert, Pierre Boisseau, Agnès Quéméner, Marianne Sigaud, Marc Fouassier, et al.. Prevalence, biological phenotype and genotype in moderate/ mild hemophilia A with discrepancy between one-stage and chromogenic factor VIII activity. Journal of Thrombosis and Haemostasis, 2011, 9 (3), pp.524-530. ⟨10.1111/j.1538-7836.2010.04174.x⟩. ⟨inserm-02441164⟩
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