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Variability in bleeding phenotype in Amish carriers of haemophilia B with the 31008 C→T mutation
Author(s) -
SHARATHKUMAR A.,
HARDESTY B.,
GREIST A.,
SALTER J.,
KERLIN B.,
HEIMAN M.,
SULKIN M.,
SHAPIRO A.
Publication year - 2009
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2008.01792.x
Subject(s) - medicine , haemophilia a , haemophilia , haemophilia b , gastroenterology , pediatrics , surgery
Summary. 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.