Recurrent VTE in patients with thrombophilia after stopping anticoagulation: a systematic review and meta-analysis

Abstract The role of thrombophilia in clinical decision-making regarding secondary venous thromboembolism (VTE) prevention is still uncertain. Therefore, we aimed to investigate the association between hereditary and acquired thrombophilia and recurrent VTE after discontinuation of anticoagulation after initial VTE treatment. We conducted a systematic review and meta-analysis to evaluate the risk of recurrent VTE in patients with and without thrombophilia including factor V Leiden (FVL) mutation, prothrombin gene G20210A mutation (PTM), antithrombin deficiency (ATD), protein C deficiency (PCD), protein S deficiency (PSD), and antiphospholipid antibody syndrome (APS). Eligible studies included randomized trials and cohort studies reporting recurrent VTE after discontinuation of anticoagulation after completion of VTE treatment. Study-level incidence rates (IR) per 100 patient-years, IR ratios, and adjusted hazard ratio were calculated or extracted and pooled using random-effects models. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. A total of 51 studies (n = 34 623 patients; 42.3% female; 33.5% with unprovoked index VTE) were included. Thrombophilias, including APS, ATD, homozygous FVL, and compound heterozygous FVL/PTM, were associated with an approximately twofold to threefold increased risk of recurrent VTE, whereas heterozygous FVL or PTM mutations were associated with a 1.5-fold increased risk. Heterogeneity and the certainty in the evidence were predominantly moderate. Evidence regarding PSD and PCD was inconclusive. Both hereditary and acquired thrombophilia are associated with an increased risk of recurrent VTE after discontinuation of anticoagulation.