Introduction:
Factor XI (FXI) deficiency is a rare bleeding disorder with a prevalence of approximately one in one million in the general population but more prevalent in the Ashkenazi Jewish community, in whom 10% are heterozygous with mild deficiencies. An ever increasing number of women are referred to hematology specialists without a clear bleeding history but a mild FXI deficiency identified initially through genetic panel testing. For instance, direct-to-consumer genetic testing has become commonplace with certain platforms such as 23andMe receiving FDA authorization to specifically include genetic testing for the most common FXI polymorphisms (i.e. F283L, E117X, and IVS14+1G>A). Unlike other inherited bleeding disorders, FXI levels do not reliably correlate with bleeding severity. There is limited data to guide the appropriate management of mild FXI deficiency during delivery. Considering postpartum hemorrhage accounts for approximately 10% of maternal mortality, we evaluated delivery outcomes among women with mild factor XI deficiency.
Methods
We performed a matched, retrospective, case control single-institution analyses. Pregnant women were identified with mild factor XI deficiency with levels between 20-70%. The control population consisted of 200 women undergoing deliveries between 2016 and 2018 identified by successive medical record numbering. Primary postpartum hemorrhage (PPH) was defined as estimated blood loss (EBL) > 1000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after delivery.
Results
Among the 40 FXI deficient women there were 71 deliveries, and outcomes were compared with 200 controls deliveries. A similar percentage of deliveries in the FXI deficient women and controls were vaginal (63% versus 63%, P=1.0). The groups were well matched for age and number of primigravid deliveries. The median estimated blood loss were the same FXI and controls for vaginal deliveries (300 mL for both groups) and caesarean deliveries (800 mL for both groups). There were no PPH recorded among the 45 vaginal deliveries in women with factor XI deficiency compared with one of 125 deliveries in the control cohort.
In contrast, women with mild factor XI deficiency undergoing cesarean delivery were approximately 2-fold more likely to develop PPH relative to controls (odds ratio 2.73, 95% CI 1.02-7.26). The overall rates of PPH among those FXI women who underwent cesarean delivery was 38.4% (10 of 26 deliveries) compared with 18.7% (14 of 75 deliveries, p=0.04). No women in the FXI deficient cohort required RBC transfusions, while three women in the control cohort required red cell transfusions.
Prior history of hemorrhage was the best predictor of PPH following cesarean delivery. The majority of women who developed PPH following caesarean delivery had a prior history of hemorrhage (7 of 10). Only two of the women with PPH received prophylactic measures prior to delivery. Among the women 16 caesarean deliveries in the FXI deficiency group without PPH, significantly fewer had a history of bleeding (2 of 16, p=0.009).
Conclusions:
In this case control study, we did not observe any cases of PPH among women with FXI deficiency who underwent a vaginal delivery but noted a greater than 2-fold increase in PPH among those women who underwent a cesarean delivery. In those women with a bleeding history the risk of PPH following cesarean section the risk of PPH was nearly 10-fold higher compared to women without a history of hemorrhage supporting the role for prophylactic measures in this high-risk group.
Disclosures
Zwicker: Portola: Consultancy; Daiichi: Consultancy; Incyte: Research Funding; Seattle Genetics: Consultancy; Bayer: Consultancy; Parexel: Consultancy; Quercegen: Research Funding.
Factor XI Deficiency in Pregnancy and Risk of Postpartum Hemorrhage
