Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors.

ABSTRACT

INTRODUCTION: Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status. AIMS: To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIXC) levels in HB carriers and assess the ratio of FIXC to other Vitamin K dependent factors (FIIC, FVIIC, FXC) as an indicator of HB carrier status. METHODS: In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIXC were described and the relationship between FIXC levels in carriers and severity of familial HB was analysed. Ratios of FIXC to FIIC, FVIIC, FXC were calculated. RESULTS: Seventy-two female HB carriers (median age 34 years; IQR 24-43) were included. Median aPTT and FIXC levels were 33.0 s [IQR 30.0-37.0] and 57 IU/dL [IQR 43-74]. Fifteen carriers (21%) had mild HB (FIXC levels of 10-40 IU/dL). FIXC levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIXC to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75. CONCLUSION: aPTT and FIXC levels were unreliable in diagnosing HB carrier status. A low ratio of FIXC to other Vitamin K dependent factors may be a useful marker of HB carrier status.