The incidence of major bleeding in adult patients with urogenital and gynecological cancer being treated with direct oral anticoagulants (DOACs): a systematic review

J Thromb Thrombolysis. 2024 Apr;57(4):630-637. doi: 10.1007/s11239-024-02956-5. Epub 2024 Mar 1.


Background: Direct oral anticoagulants (DOACs) are the mainstay of treatment for venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF), with or without an underlying cancer. Patients with cancer have a 2-3-fold increase in risk for bleeding complications compared to non-cancer patients taking anticoagulant therapy, however the incidence of bleeding for urogenital and gynecological cancers on DOACs are uncertain.

Aims: To assess the bleeding risk associated with the use of DOACs in patients with urogenital and/or gynecological cancers.

Method: We conducted a systematic review of randomized controlled trials (RCTs) and prospective cohort studies to address the safety of DOACs for VTE and AF when used in patients with urogenital and/or gynecological malignancy. The primary outcomes assessed were major and clinically relevant non-major (CRNMB) bleeding, with minor bleeding considered as a secondary outcome. MEDLINE, EMBASE and COCHRANE Central Registry of Controlled Trials were searched up to and including Oct 28, 2022. The study protocol was registered in PROSPERO (CRD42022370981). Studies were independently assessed for inclusion and data extracted in duplicate.

Result: Seven studies met our inclusion criteria (Fig. 1): 2 RCTs and 5 prospective cohort studies. A total of 676 patients treated with DOACs were included, 628 (92.8%) had VTE and 48 (7.1%) had AF. In patients with VTE treated with DOACs, the pooled major bleeding rate was 2.1%, 95% confidence intervals (CI) 0.9-3.3% (Fig. 2). Pooled estimates could not be determined for AF patients given small event and patient numbers.

Conclusion: Major bleeding rates in urogenital and/or gynecological cancer patients treated with DOACs are similar to that of the general cancer population.

Keywords: Bleeding; Cancer-associated venous thromboembolism; Direct oral anticoagulant; Gynecologic cancer; Systematic review; Urogenital cancer.

Publication types

  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / therapeutic use
  • Hemorrhage / chemically induced
  • Humans
  • Incidence
  • Neoplasms* / complications
  • Venous Thromboembolism* / drug therapy


  • Anticoagulants