Contrary to current guidance, antenatal factor IX levels increase in female carriers of hemophilia B

BACKGROUND: Current international hemophilia guidelines state that antenatal factor (F)IX (FIX) levels do not increase in carriers of hemophilia B (HB). However, the evidence base for this statement comes from 10 publications (many of which are isolated case reports) that included both baseline and antenatal plasma FIX coagulant activity (FIX:C) levels in a total of only 30 HB carriers. OBJECTIVES: To review the change, if any, in antenatal FIX:C levels in a large cohort of Irish HB carriers. METHODS: Following ethical approval, all parous HB carriers were identified from the Irish registry. All pregnancies and related clinical data (baseline and antepartum FIX levels, bleeding scores, genetic analysis) from 1999-2025 were recorded for each hemophilia carrier. RESULTS: Forty-nine parous HB carriers (87 pregnancies) were identified with baseline and antepartum plasma FIX:C levels. Overall, pregnancy was associated with a significant increase in plasma FIX:C levels in HB carriers compared with baseline (mean baseline FIX:C 0.54 IU/mL vs antepartum FIX:C 0.89 IU/mL, P < .0001). Importantly, a significant increase in plasma FIX:C levels was also observed in women with mild HB (n = 13, mean baseline FIX:C 0.27 IU/mL vs antepartum FIX:C 0.51 IU/mL, P = .0002). In all women with baseline FIX:C 0.30 to 0.49 IU/mL (n = 6, 12 pregnancies), FIX:C increased to >0.50 IU/mL, facilitating neuraxial anesthesia. CONCLUSIONS: Contrary to published guidance, FIX:C levels increase during pregnancy in carriers of HB. This work challenges current approaches and counseling provided to carriers of HB and highlights the importance of evaluating FIX:C levels to guide hemostatic management of delivery.