Introduction Factor XI deficiency is an autosomal recessive bleeding disorder that poses challenges in peripartum management due to the poor correlation between FXI levels and bleeding risk. Neuraxial anesthesia (NA) is less frequently administered to women with FXI < 0.4 IU/mL compared to those ≥ 0.4 IU/mL due to bleeding concerns. Risk assessment and hemostatic strategies for safe anesthesia remain controversial. Additionally, postpartum hemorrhage (PPH) is described in 11–22% of cases, but guidance on effective prevention is limited.

Methods We conducted a retrospective chart review of pregnant women with FXI deficiency who gave birth at Mount Sinai Hospital, Toronto, between January 1, 2002, and December 31, 2024 to determine the factor XI levels at which NA was administered and rates of PPH. Patients were identified using ICD-10 codes and FXI levels from the coagulation laboratory. FXI deficiency was defined as FXI activity <0.70 IU/mL or a confirmed FXI gene mutation. Patients were categorized as severe (<0.15 IU/mL), moderate (0.15–0.39 IU/mL), or mild (0.40–0.70 IU/mL) deficiency. Data collection included age, ethnicity, parity, delivery mode, type of anesthesia (NA or general anesthesia (GA), estimated blood loss, use of hemostatic agents (e.g., FXI concentrate, Fresh frozen plasma (FFP), Tranexamic acid (TXA), Red blood cells (RBC), and FXI levels (baseline and post-treatment if available). Bleeding phenotype was assessed using the Bolton-Maggs classification. PPH was defined as ≥1000 mL blood loss or signs of hypovolemia within 24 hours (primary) or up to 12 weeks (secondary). Continuous variables were summarized as mean (SD) or median (IQR); categorical variables as counts and percentages. The study was approved by the local Research Ethics Board.

Results We identified 20 women with FXI deficiency who had 35 deliveries (13 cesarean, 22 vaginal), with a median FXI level of 0.38 IU/mL. Deliveries occurred in patients with severe (<0.15 IU/mL, n=13), moderate (n=5), and mild (n=17) deficiencies. FXI genotype was homozygous in 15%, heterozygous in 25%, and unknown in 60%. FXI deficiency was diagnosed by family history (6%), ethnic screening (27%), bleeding investigation (51%, with 30% due to history of obstetric bleeding), and was unknown in 17%.

Overall, NA was used in 31/35 (89%) deliveries. Of the 22 vaginal deliveries, 21 (95.4%) received NA, and one received remifentanil patient-controlled analgesia (PCA) due to personal choice. Of the 13 cesarean deliveries, 10 received NA and 3 had GA: one declined NA on the background of limited FXI concentrate availability, one refused FXI replacement and NA was avoided in a patient with Ehlers-Danlos syndrome due to the additional bleeding risk. FXI replacement (FFP or factor XI concentrate) was administered in 14 deliveries (12 severe, 2 moderate; median baseline FXI 0.07 IU/mL, IQR 0.058 IU/ml). Mean dose of FXI concentrate (n=13) was 24 IU/kg (range 13.8–40.2) and FXI level increased by a mean of 1.7 IU/dL per IU/kg, SD 0.4 IU/dL. Post-replacement FXI levels (n=8) ranged from 0.23 to 0.68 IU/mL. No bleeding or thrombotic complications occurred.

In this cohort, 20/35 (57%) had a bleeding phenotype. Five PPH events occurred, with 4 primary and 1 secondary. Three women with PPH had a known bleeding phenotype. PPH severity varied, with a higher median blood loss (660 mL) in PPH cases compared to those without (425 mL), and three women required RBC. Two patients required reoperation and one required readmission due to secondary PPH. Additionally, epidural catheters were retained longer in one patient due to postoperative bleeding and in three patients due to low factor XI levels during the postpartum period (range 0.04-0.37 IU/ml).

Conclusions In this report 37% had severe FXI deficiency and 57% had a bleeding phenotype. NA was offered to nearly all patients, contrasting with reports of up to 33% exclusion due to FXI levels. Replacement to target FXI levels of 0.3–0.4 IU/mL enabled safe NA without supratherapeutic levels or thromboembolic events. Two patients with FXI levels of 0.28 and 0.27 IU/ml without a bleeding phenotype also received NA without bleeding complications, supporting a case-by-case approach regarding eligibility for NA. Our PPH rate was 14%, within the previously reported 11–22% range, and did not correlate with FXI levels. No PPH occurred in patients receiving FXI concentrate.

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2025
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