Factor XI (FXI) deficiency is a rare bleeding disorder. In the general population, prevalence is estimated to be 1:1 million people for the homozygous presentation (PMID: 25100430). Nonetheless, in individuals of Ashkenazi and Iraqi Jewish ancestry, the prevalence of heterozygous cases is approximately 8% (PMID: 7811996). However, these numbers may be underestimates, as some patients are asymptomatic and, so, not accounted for. Pregnant women are a special population, as FXI deficiency may pose an increased risk during pregnancy and delivery. This study describes the experience of a General Hematology Outpatient Service to which pregnant women with FXI deficiency are referred. This case series aims to describe the clinical course of these patients, and any complications and interventions they may have experienced during pregnancy and delivery.
This retrospective study identified a group of 49 patients with FXI deficiency who were evaluated by a single practitioner at the Hematology Outpatient Service at Mount Sinai West, in New York City, between October 2016 and February 2020. Patients were found to be FXI deficient on routine genetic screening early in their obstetric care. Their charts were reviewed, including epidemiological data, notes from Hematology and Obstetric Clinics and from the admission for delivery and laboratory results. Four patients were excluded from the final analysis: 3 who were not pregnant, and 1 who did not have FXI deficiency. Patients were seen in by the Hematology Service at least once during their pregnancy. FXI activity was measured at least twice during pregnancy: at the initial visit, and at about gestational week 37. The data were analyzed to obtain the mean and standard deviation for the most relevant clinical parameters. A comparison between FXI activity at the first visit and at last visit near term was made with a paired T-test.
The included group of 45 patients presented a mean age at delivery of 34.09 years (range 26-45 years). Genetic data was available for 42 patients, with 2.38% being homozygous. Ethnicities were described for 39 patients, and 71.79% were identified as Ashkenazi Jewish. Among 39 patients who had their FXI gene (gene NM_000128.3) mutations described, the c.901T>C, p.F301L mutation was present in 61.54% of them. The mean FXI activity measured in the first appointment was 60.18%, (range 4-220%), while the mean FXI activity in week 37 of pregnancy was 52.08% (range 13-118%). When comparing the FXI activity on the first appointment and around week 37, no statistically significant difference was found (p=0.17). Four patients received preventive interventions on delivery. One patient was treated with Tranexamic Acid (TXA) and Fresh Frozen Plasma (FFP) transfusion due to a FXI activity of 21% on week 37, and received general anesthesia. Two patients received transfusion of FFP alone: 1 of them due to an elevated aPTT (57.4s) on delivery date, with no anesthesia on delivery; and the other one as a preventive measure in a patient with a FXI of 45% on week 37, but who was planned for a neuraxial block. A FXI activity of 40% is the cutoff for a neuraxial block by the Anesthesiology Department at our hospital. One patient was treated with TXA due to a borderline FXI activity of 42% and a personal history of bleeding on surgical procedures. She had an opioid patient-controlled analgesia on delivery. For the detailed data regarding mean blood loss on delivery, postpartum blood loss, and complete Hematologic and Obstetric data, see tables 1 and 2, and figures 1 and 2. Figure 3 presents a data comparison between the 2 most common genotypes observed.
In our case series, no patient experienced bleeding complications during pregnancy or delivery. Monitoring FXI levels and aPTT throughout pregnancy and before delivery remains as the standard medical care (PMID: 27699729). The difference between FXI levels earlier in pregnancy and near delivery was not statistically significant, as noted in previous studies (PMID: 15199489). Checking FXI activity throughout pregnancy may not be necessary, and one measurement might be enough. Further study might be able to answer this question, as the optimal management of these patients remains a work in progress. Evidence for a reliable threshold FXI activity at which neuraxial anesthesia could be safely performed will be a valuable finding. Continuation of our study will allow for further data regarding the management of FXI deficient pregnant women.
Disclosures
No relevant conflicts of interest to declare.
Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction
