Venous thromboembolism and bleeding rates in pregnant and postpartum patients with sickle cell disease

Abstract Background: Venous thromboembolism (VTE) and postpartum hemorrhage (PPH) are major causes of increased maternal morbidity observed in people with sickle cell disease (SCD). The reported incidence of VTE in pregnant and postpartum patients with SCD is 2-17% compared to 0.05-0.12% antepartum and 0.07-0.2% postpartum in the general population. The odds of PPH are ~2x greater in patients with SCD compared to Black patients without SCD, raising concern about routine thromboprophylaxis during and after pregnancy. Existing data on VTE and bleeding risks have significant limitations with a wide range of reported VTE incidence and limited reporting of anticoagulant thromboprophylaxis or aspirin (ASA) use, SCD phenotype, and pregnancy characteristics. We report results from a regional, retrospective cohort describing rates of VTE, bleeding, and thromboprophylaxis use in pregnant and postpartum patients with SCD. Methods: We performed an IRB-approved electronic medical record analysis that included all patients with SCD and one or more pregnancies between 2015 and 2025 at the integrated Mass General Brigham hospital system. Demographics, medication use, laboratory data, pregnancy and SCD characteristics, and VTE and bleeding events during pregnancy and the postpartum period—defined as time of conception to 90 days postpartum—were recorded. Primary objectives were to determine rates of VTE, bleeding, and thromboprophylaxis use. Continuous variables were summarized as median with interquartile range (IQR), and categorical variables as proportions (95% confidence intervals [CI]); group comparisons for categorical data used chi-square tests. Results: Forty eligible patients with 60 pregnancies were identified and included in the analytic cohort. 70% (28/40) identified as Black or African American and 18% (7/40) identified as Hispanic. Median age at delivery was 33.8 years (IQR: 27.4-36.7), and median pre-pregnancy BMI was 24.7 kg/m2 (IQR: 22.7-28.4). Genotypes included HbSS (63%, 25/40), HbSC (23%, 9/40), HbSβ0(8%, 3/40), HbSβ+(5%, 2/40), and HbS/Quebec-Chori (3%, 1/40). Antepartum or postpartum thromboprophylaxis was prescribed in only 15% (95% CI: 7-29%, 9/60) of pregnancies, predominantly for history of VTE (n=8/9). ASA was prescribed in 68% (95% CI: 49-93%, 41/60) of pregnancies. VTE occurred in 17% (95% CI: 8-31%, 10/60) of pregnancies. Of the VTE events, 90% (9/10) included a pulmonary embolism diagnosis, and 50% (5/10) occurred postpartum (median: 7 days; IQR: 3-15). At the time of VTE diagnosis, 3 patients were taking ASA and 1 was prescribed 40mg enoxaparin daily. All were subsequently treated with anticoagulation at therapeutic dosing. There was no difference in rate of VTE by Hb genotype (p=0.12). No arterial thromboses or deaths were reported. Red blood cell (RBC) transfusion was administered in 67% (95% CI: 48-91%, 40/60) of pregnancies with 52% (95% CI: 35-73%, 31/60) receiving at least one RBC unit within 72 hours of delivery. Of deliveries with reported estimated blood loss (EBL) data, 57% (95% CI: 38-83%, 28/49) had EBL ≥500mL, and 20% (95% CI: 10-38%, 10/49) had EBL ≥1000mL (current EBL criteria for PPH). Major or clinically relevant non-major bleeding occurred in 7% (95% CI: 2-17%, 4/60) of pregnancies with 75% (3/4) of events occurring in patients receiving therapeutic anticoagulation for treatment of pregnancy-associated VTE. Bleeding impacted 30% (3/10) of therapeutic anticoagulation prescriptions. Discussion: This report characterizes VTE events, bleeding events, and thromboprophylaxis use in a cohort of pregnant and postpartum patients with SCD at a large, academic referral center. VTE occurred in 17% of patients in this cohort, much higher than the typically reported incidence in the general population. Frequency of reported EBL ≥1000mL during delivery (current EBL criteria for PPH) and of transfusions within 72 hours of delivery was also high. Antepartum or postpartum thromboprophylaxis was prescribed infrequently and predominantly used in patients with prior VTE history. These data emphasize the high risk of both thrombosis and bleeding in pregnant and postpartum patients with SCD, complicating routine thromboprophylaxis use. Ongoing multicenter data collection will allow for improved estimates of VTE and bleeding as well as identification of associated risk factors which will inform the design of a randomized controlled trial to evaluate the efficacy and safety of thromboprophylaxis in this population.