PDF herunterladen
Hamostaseologie 2022; 42(05): 337-347
DOI: 10.1055/a-1891-8187
Review Article

Bleeding Issues in Women Under Oral Anticoagulation

Lida Kalmanti
1   Center of Thrombosis and Hemostasis, Johannes Gutenberg University Mainz, Mainz, Germany
,
Edelgard Lindhoff-Last
2   Cardioangiology Center Bethanienhospital, Coagulation Center and Coagulation Research Center, Frankfurt, Germany
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists. These findings come from retrospective or prospective single-center studies and post hoc analysis of regulatory studies in which HMB was not a predefined safety outcome. In most of these publications, there is a lack of information about the use of different contraceptive methods which can influence HMB. Another limitation is the various definitions of HMB, which makes comparison between studies regarding the incidences of HMB difficult.

Therefore, prospective studies are urgently needed to investigate the severity and duration of unaffected menstrual bleeding under oral anticoagulation independently of oral contraceptives or intrauterine devices. An ongoing multicenter German registry is aiming to compare the incidence of unaffected HMB in consecutive women of reproductive age (18–50 years) treated with different DOACs because of venous thromboembolism.

When HMB occurs during oral anticoagulation, management includes interruption or dose reduction of anticoagulation with the danger of recurrent venous thrombosis, switch to another oral anticoagulant, or additional use of the antifibrinolytic agent tranexamic acid with the potential risk of thrombosis. Concomitant use of either oral hormonal contraceptive therapy or hormone-releasing intrauterine systems can also reduce HMB.

Keywords

abnormal uterine bleeding - heavy menstrual bleeding - PBAC score - direct oral anticoagulants - venous thrombosis


Publikationsverlauf

Eingereicht: 05. Februar 2022

Angenommen: 28. Juni 2022

Artikel online veröffentlicht:
02. November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Zakherah MS, Sayed GH, El-Nashar SA, Shaaban MM. Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnostic accuracy compared to alkaline hematin. Gynecol Obstet Invest 2011; 71 (04) 281-284
    CrossrefPubMedGoogle Scholar
  • 2 Jacobson-Kelly AE, Samuelson Bannow BT. Abnormal uterine bleeding in users of rivaroxaban and apixaban. Hematology (Am Soc Hematol Educ Program) 2020; 2020 (01) 538-541
    CrossrefPubMedGoogle Scholar
  • 3 Higham JM, O`Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97 (08) 734-739
    CrossrefPubMedGoogle Scholar
  • 4 Rodeghiero F, Tosetto A, Abshire T. et al; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
    Google Scholar
  • 5 Pathare A, Al Omrani S, Al Hajri F, Al Obaidani N, Al Balushi B, Al Falahi K. Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire. Int J Lab Hematol 2018; 40 (02) 175-180
    CrossrefPubMedGoogle Scholar
  • 6 Samuelson Bannow B. Management of heavy menstrual bleeding on anticoagulation. Hematology (Am Soc Hematol Educ Program) 2020; 2020 (01) 533-537
    CrossrefPubMedGoogle Scholar
  • 7 Klok FA, Schreiber K, Stach K. et al. Oral contraception and menstrual bleeding during treatment of venous thromboembolism: expert opinion versus current practice: combined results of a systematic review, expert panel opinion and an international survey. Thromb Res 2017; 153: 101-107
    CrossrefPubMedGoogle Scholar
  • 8 Huq FY, Tvarkova K, Arafa A, Kadir RA. Menstrual problems and contraception in women of reproductive age receiving oral anticoagulation. Contraception 2011; 84 (02) 128-132
    CrossrefPubMedGoogle Scholar
  • 9 Själander A, Friberg B, Svensson P, Stigendal L, Lethagen S. Menorrhagia and minor bleeding symptoms in women on oral anticoagulation. J Thromb Thrombolysis 2007; 24 (01) 39-41
    CrossrefPubMedGoogle Scholar
  • 10 Martinelli I, Lensing AW, Middeldorp S. et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016; 127 (11) 1417-1425
    CrossrefPubMedGoogle Scholar
  • 11 Agnelli G, Becattini C, Meyer G. et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020; 382 (17) 1599-1607
    CrossrefPubMedGoogle Scholar
  • 12 Huisman MV, Ferreira M, Feuring M, Fraessdorf M, Klok FA. Less abnormal uterine bleeding with dabigatran than warfarin in women treated for acute venous thromboembolism. J Thromb Haemost 2018; 16 (09) 1775-1778
    CrossrefPubMedGoogle Scholar
  • 13 Scheres L, Brekelmans M, Ageno W. et al. Abnormal vaginal bleeding in women of reproductive age treated with edoxaban or warfarin for venous thromboembolism: a post hoc analysis of the Hokusai-VTE study. BJOG 2018; 125 (12) 1581-1589
    CrossrefPubMedGoogle Scholar
  • 14 De Crem N, Peerlinck K, Vanassche T. et al. Abnormal uterine bleeding in VTE patients treated with rivaroxaban compared to vitamin K antagonists. Thromb Res 2015; 136 (04) 749-753
    CrossrefPubMedGoogle Scholar
  • 15 Bryk AH, Piróg M, Plens K, Undas A. Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K antagonists and the risk of recurrent venous thromboembolism. Vascul Pharmacol 2016; 87: 242-247
    CrossrefPubMedGoogle Scholar
  • 16 Beyer-Westendorf J, Michalski F, Tittl L, Hauswald-Dörschel S, Marten S. Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series. Lancet Haematol 2016; 3 (10) e480-e488
    CrossrefPubMedGoogle Scholar
  • 17 Myers B, Webster A. Heavy menstrual bleeding on rivaroxaban - comparison with apixaban. Br J Haematol 2017; 176 (05) 833-835
    CrossrefPubMedGoogle Scholar
  • 18 Young AM, Marshall A, Thirlwall J. et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-2023
    CrossrefPubMedGoogle Scholar
  • 19 Boonyawat K, Lensing AWA, Prins MH. et al. Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: comparison of high- and low-dose rivaroxaban with aspirin. Res Pract Thromb Haemost 2021; 5 (02) 308-313
    CrossrefPubMedGoogle Scholar
  • 20 Male C, Lensing AWA, Palumbo JS. et al; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7 (01) e18-e27
    CrossrefPubMedGoogle Scholar
  • 21 Brekelmans MP, Scheres LJ, Bleker SM. et al. Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin. Thromb Haemost 2017; 117 (04) 809-815
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 22 Godin R, Marcoux V, Tagalakis V. Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism. Vascul Pharmacol 2017; 93–95: 1-5
    CrossrefPubMedGoogle Scholar
  • 23 Weaver J, Shoaibi A, Truong HQ. et al. Comparative risk assessment of severe uterine bleeding following exposure to direct oral anticoagulants: a network study across four observational databases in the USA. Drug Saf 2021; 44 (04) 479-497
    CrossrefPubMedGoogle Scholar
  • 24 Steffel J, Verhamme P, Potpara TS. et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
    CrossrefPubMedGoogle Scholar
  • 25 Hamulyák EN, Wiegers HMG, Scheres LJJ. et al. Heavy menstrual bleeding on direct factor Xa inhibitors: rationale and design of the MEDEA study. Res Pract Thromb Haemost 2020; 5 (01) 223-230
    CrossrefPubMedGoogle Scholar
  • 26 Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011; 343: d6423
    CrossrefPubMedGoogle Scholar
  • 27 Franik S, Bauersachs R, Beyer-Westendorf J. et al. Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020). Geburtshilfe Frauenheilkd 2021; 81 (02) 152-182
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 O'Brien SH. Evaluation and management of heavy menstrual bleeding in adolescents: the role of the hematologist. Hematology (Am Soc Hematol Educ Program) 2018; 2018 (01) 390-398
    CrossrefPubMedGoogle Scholar
  • 29 Stewart A, Cummins C, Gold L, Jordan R, Phillips W. The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review. BJOG 2001; 108 (01) 74-86
    PubMedGoogle Scholar
  • 30 Mansour D. Modern management of abnormal uterine bleeding: the levonorgestrel intra-uterine system. Best Pract Res Clin Obstet Gynaecol 2007; 21 (06) 1007-1021
    CrossrefPubMedGoogle Scholar
  • 31 Meaidi A, Mørch L, Torp-Pedersen C, Lidegaard O. Oral tranexamic acid and thrombosis risk in women. EClinicalMedicine 2021; 35: 100882
    CrossrefPubMedGoogle Scholar
  • 32 Ferreira M, Barsam S, Patel JP. et al. Heavy menstrual bleeding on rivaroxaban. Br J Haematol 2016; 173 (02) 314-315
    CrossrefPubMedGoogle Scholar