The aim of this study was to characterize the variability of
bleeding phenotype and its association with plasma
factor IX coagulant activity (FIX:C) in
haemophilia B carriers in a large Amish pedigree with a unifying genetic mutation, C-to-T transition at base 31008 of the
factor IX gene (Xq27.1-27.2). A cross-sectional survey of
haemophilia B carriers included a multiple choice questionnaire evaluating symptoms of mucocutaneous
bleeding, joint
bleeding and
bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH), dental extractions and invasive surgeries]. Severity of
bleeding was graded as 0 to 4, 0 being no
bleeding whereas 4 being severe
bleeding. Association between total
bleeding scores and the FIX:C was evaluated. Sixty-four
haemophilia B carriers participated in this study. Median age: 18 years (range 1-70 years); median
bleeding score: 1 (range 0-8). Besides PPH, isolated symptoms of bruising,
epistaxis,
menorrhagia and postsurgical
bleeding including dental extraction were not associated with lower FIX:C.
Bleeding score >/=3 was associated with involvement of at least two
bleeding sites and a lower mean FIX:C of 42 +/- 10.3% (95% CI 36.4-47.7) while a score >3 had involvement of </=2 sites and higher mean FIX:C of 54.9 +/- 21.5% (95% CI 49-61), P = 0.005. Subcutaneous haematoma formation and
bleeding after haemostatic stress requiring treatment were associated with
bleeding scores >/=3. Phenotypic variability existed among the carriers of
haemophilia B who belonged to a single pedigree carrying a single unifying mutation. The utility of
bleeding scores to define
bleeding phenotype precisely in
haemophilia B carriers needs further evaluation.