The Risk of Bleeding in Pregnant Women with Acute Venous Thromboembolism Treated with Anticoagulants

Introduction Women are at an increased risk of venous thromboembolism (VTE) during pregnancy and the postpartum period. VTE, which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), complicates 1 to 2 of 1000 pregnancies and is an important cause of maternal morbidity and mortality. The risk of VTE during pregnancy is increased five to ten-fold compared to the non-pregnant woman of comparable age. During pregnancy, subcutaneous weight-adjusted low-molecular-weight-heparin (LMWH) is the standard anticoagulation therapy for acute VTE. Women receive a minimum of 3 months of LMWH with treatment generally extended throughout pregnancy and for at least 6 weeks following delivery given the additional increased VTE risk during the postpartum period.

Variable estimates are reported in the literature pertaining to the risk of bleeding in pregnant patients treated with therapeutic anticoagulation. The risk of major bleeding, as defined by the study, ranges between 2.9 and 30.0% according to a recent systematic review of the literature. The ability to make inference is limited by the small number of patients included in the studies and the substantial heterogeneity of bleeding definitions used. The paucity of data doesn't allow healthcare providers to accurately estimate the risk of bleeding in this population and prevents adequate patient counselling. As such, we conducted a population-based cohort study to evaluate the risk of bleeding events among pregnant women with acute VTE treated with LMWH anticoagulants.

Methods We conducted a retrospective cohort study using data from electronic healthcare databases from the province of Quebec, Canada, including the Régie de l'assurance maladie du Québec (RAMQ), the Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière (Med-Echo) and the Institut de la statistique du Québec (ISQ). From an inception cohort of Quebec residents with a diagnosis of incident VTE between January 1, 1998, and December 31, 2015, we created a study cohort of pregnant women diagnosed with VTE during pregnancy who received a prescription for LMWH within 15 days of the incident event. When the gestational age of pregnant women was not available in the database, a previously described algorithm was used to extrapolate the date of conception according to the delivery outcome. Women were followed until an inpatient diagnosis of bleeding within 30 days of delivery or censoring due to discontinuation of LMWH use, cessation of medication coverage eligibility, death, or the end of the study period. Major bleeding was defined as a hospitalization for bleeding within the study period.

Results Of the 325,560 patients included in the inception VTE cohort, 259 pregnant patients remained after the exclusion criteria were applied. The mean age of patients was 29 years-old, 80.9% of patients had a DVT and 19.5% had a PE. 72.6% of patients received Dalteparin, while the other patients received Tinzaparin or Enoxaparin. In total, 20 patients (7.7%) experienced bleeding requiring hospitalization during the study period, 5 of which were antepartum bleeding events (1.9%). The incidence rate of major bleeding was 310.5 per 1,000 person-years (95% CI 189.6-479.5). There was no bleeding-related or all-cause related mortality in this cohort.

Conclusion This study provides a population-derived estimate of bleeding in pregnant women treated with therapeutic anticoagulation for VTE during pregnancy. This study has some limitations. First, data is not available for women who do not use medical services during pregnancy, those who give birth outside a hospital setting. However, given the free universal healthcare system in the province of Quebec, the effect of this on our result is expected to be minimal. Second, the RAMQ database provides information on individuals adherent to the RAMQ drug plan and welfare recipients, but not on individuals who are covered by private insurance. This may affect the generalizability of our study findings if socioeconomic status is an effect modifier. Our results show that Dalteparin is the most used LMWH in pregnancy. This study provides an estimate of bleeding events that are clinically significant and require hospitalization. Further studies are needed to evaluate the factors associated with increased bleeding in this patient population.

No relevant conflicts of interest to declare.