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.