Recurrent VTE in Pregnant Woman with Previous Personal History of VTE: A Systematic Review and Meta-Analysis

Introduction: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality during pregnancy and the postpartum periods. Despite that, the prevention and management of VTEs in pregnant patients remains an area of great debate, particularly among those with a personal VTE history. There is no solid evidence behind the current practice guidelines on the prevention of VTE in pregnancy as most data comes from studies focusing on non-pregnant patients or from small studies. It has been suggested that without low molecular weight heparin (LMWH) thromboprophylaxis, women with a personal history of VTE may have a 2% to 10% absolute risk of developing recurrent VTE during a subsequent pregnancy. We conducted a systematic review to evaluate the risk of VTE recurrence during pregnancy for pregnant patients with prior personal history of VTE and the effect of LMWH on such risk.

Materials and Methods: MEDLINE and EMBASE were searched between January 2000 to December 2020. We included studies that evaluated pregnant patients with previous personal VTE history (deep vein thrombosis (DVT) and pulmonary embolism (PE) only) that assessed venous thromboembolism recurrence and/or bleeding complication and/or pregnancy outcomes. Study selection and data extraction was conducted by 3 reviewers and discrepancies resolved by consensus. A meta-analysis of proportions was done through a Freeman-Tukey transformation using random effect models. Groups were analyzed according to prophylaxis strategy. Heterogeneity between studies was assessed by Cochrane Q and Higgins I ² analyses. Publication bias was assessed using Eggers' tests and funnel plot.

Results. Of 6934 potential studies, 27 were included in this systematic review. The studies included 3631 pregnant patients with a previous history of DVT or PE, regardless of the presence of thrombophilia. We found a wide variability in thromboprophylaxis practices which included mostly low molecular weight heparin using weight-based, risk category-based, anti-Xa based, fixed, or trimester-adjusted doses . In studies that categorized patients into provoked, estrogen associated and unprovoked, most patients had an estrogen-associated previous VTE.

The estimated pooled proportions of VTE recurrence were 2.7% (95% CI 1.8-3.7; I ² 55.5%) in patients who were consistently on anticoagulation during pregnancy (pre- and post-partum), 2.6% (95% CI 0.6-5.9; I ² not estimable) in patients who received anticoagulation in the postpartum period only, and 25.3% (95% CI 8.9-46.6; I ² 93.2%) in patients who were not on anticoagulation. No comparison could be done on the different dosage strategies due to the limited number of studies and wide variety of strategies. Due to limited data available, bleeding complications and pregnancy outcomes could not be assessed.

Conclusion. In patients with a previous VTE history receiving prophylactic anticoagulation (either both pre- and post-partum or post-partum only), the estimates of VTE recurrence were significantly lower than that for patients who did not receive prophylaxis, however, a direct comparison was not possible. The optimal thromboprophylaxis strategy remains unknown.