The risk of major bleeding in patients with factor V Leiden or prothrombin G20210A gene mutation while on extended anticoagulant treatment for venous thromboembolism

J Thromb Haemost. 2023 Mar;21(3):553-558. doi: 10.1016/j.jtha.2022.12.021. Epub 2022 Dec 30.

Abstract

Background: Thrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants.

Objectives: To assess whether thrombophilia is protective against bleeding.

Methods: This multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers).

Results: Of 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03).

Conclusion: This study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.

Keywords: anticoagulants; bleeding; factor V leiden; prothrombin G20210a thrombophilia; thrombophilia.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants
  • Factor V / genetics
  • Hemorrhage / complications
  • Humans
  • Mutation
  • Prospective Studies
  • Prothrombin / genetics
  • Risk Factors
  • Thrombophilia* / genetics
  • Venous Thromboembolism* / epidemiology

Substances

  • factor V Leiden
  • Factor V
  • Prothrombin
  • Anticoagulants

Supplementary concepts

  • Thrombophilia, hereditary

Grants and funding