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

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 following initial VTE treatment. A systematic review and meta-analysis was conducted 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, protein C and protein S deficiencies (ATD, PCD, PSD), and antiphospholipid antibody syndrome (APS). Eligible studies included randomized trials and cohort studies reporting recurrent VTE after discontinuation of anticoagulation following completion of VTE treatment. Study-level incidence rates (IR) per 100 patient-years, incidence rate ratios (IRR), and adjusted hazard ratio (aHR) were calculated or extracted and pooled using random-effects models. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A total of fifty-one 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 2-3-fold increased risk of recurrent VTE whereas heterozygous FVL or PTM mutations were associated with a 1.5-fold increased risk. Heterogeneity and the certainty of evidence was 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.