Major differences in bleeding symptoms between factor VII deficiency and hemophilia B |
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| Authors: | F BERNARDI A DOLCE† M PINOTTI A D SHAPIRO‡ E SANTAGOSTINO§ F PEYVANDI§ A BATOROVA¶ M LAPECORELLA J F SCHVED†† J INGERSLEV‡‡ G MARIANI FOR THE INTERNATIONAL FACTOR VII DEFICIENCY STUDY GROUP |
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| Institution: | Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara;;National Institute of Statistics, Rome, Italy;;Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA;;Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Milan, Italy;;The National Hemophilia Center, Institute of Hematology and Blood Transfusion, University Hospital, Bratislava, Slovakia;;Internal Medicine &Hematology, Department of Internal Medicine and Public Health, L' Aquila University, L' Aquila, Italy;;Hemophilia Centre, CHU Montpellier, France;;and Centre for Hemophilia and Thrombosis, Aarhus University Hospital, Skejby, Aarhus N, Denmark |
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| Abstract: | Summary. Background: The autosomally-inherited factor VII (FVII) deficiency and X-linked hemophilia B offer an attractive model to investigate whether reduced levels of FVII and FIX, acting in the initiation and amplification of coagulation respectively, influence hemostasis to a different extent in relation to age and bleeding site. Methods: Hemophilia B patients ( n = 296) and FVII-deficient males ( n = 109) were compared for FVII/FIX clotting activity, F7/F9 genotypes and clinical phenotypes in a retrospective, multi-centre, cohort study. Results: Major clinical differences between diseases were observed. Bleeding occurred earlier in hemophilia B (median age 2.0 years, IR 0.9–5.0) than in FVII deficiency (5.2 years, IR 1.9–15.5) and the bleeding-free survival in FVII deficiency was similar to that observed in 'mild' hemophilia B ( P = 0.96). The most frequent disease-presenting symptoms in hemophilia B (hematomas and oral bleeding) differed from those in FVII deficiency (epistaxis and central nervous system bleeding). Differences were confirmed by analysis of FVII-deficient women. Conclusions: Our data support the notion that low FVII levels sustain hemostasis better than similarly reduced FIX levels. On the other hand, minute amounts of FVII, differently to FIX, are needed to prevent fatal bleeding, as indicated by the rarity of null mutations and the associated life-threatening symptoms in FVII deficiency, which contributes towards shaping clinical differences between diseases in the lowest factor level range. Differences between diseases are only partially explained by mutational patterns and could pertain to the specific roles of FVII and FIX in coagulation phases and to vascular bed-specific components. |
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| Keywords: | bleeding disease-presenting symptoms FVII deficiency hemophilia B |
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