Download PDF
Thromb Haemost 2017; 117(04): 809-815
DOI: 10.1160/TH16-11-0874
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin

Marjolein P.A. Brekelmans   *
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Luuk J.J. Scheres   *
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
2   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
,
Suzanne M. Bleker
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Barbara A. Hutten
3   Department of Clinical Epidemiology, Academic Medical Center, Amsterdam, the Netherlands
,
Anne Timmermans
4   Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, the Netherlands
,
Harry R. Büller
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Saskia Middeldorp
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 22 November 2016

Accepted after major revision: 14 January 2017

Publication Date:
13 November 2017 (online)

    Permissions and Reprints

Summary

Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7–2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8–6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5–11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/ warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.

Keywords

Anticoagulants - apixaban - warfarin - venous thromboembolism - abnormal - vaginal bleeding

* Both authors contributed equally to this manuscript.


 

  • References

  • 1 Bleker SM, Coppens M, Middeldorp S. Sex, thrombosis and inherited thrombophilia. Blood Rev 2014; 28: 123-133
    CrossrefPubMedGoogle Scholar
  • 2 Naess IA, Christiansen SC, Romundstad P. et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5: 692-699
    CrossrefPubMedGoogle Scholar
  • 3 Roach RE, Lijfering WM, Rosendaal FR. et al. Sex difference in risk of second but not of first venous thrombosis: paradox explained. Circulation 2014; 129: 51-56
    CrossrefPubMedGoogle Scholar
  • 4 van Es N, Coppens M, Schulman S. et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124: 1968-1975
    CrossrefPubMedGoogle Scholar
  • 5 Alotaibi GS, Almodaimegh H, McMurtry MS. et al. Do women bleed more than men when prescribed novel oral anticoagulants for venous thromboembolism? A sex-based meta-analysis. Thromb Res 2013; 132: 185-189
    CrossrefPubMedGoogle Scholar
  • 6 Ferreira M, Barsam S, Patel JP. et al. Heavy menstrual bleeding on rivaroxaban. Br J Haematol 2016; 173: 314-315
    CrossrefPubMedGoogle Scholar
  • 7 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: 749-753
    CrossrefPubMedGoogle Scholar
  • 8 Martinelli I, Lensing AW, Middeldorp S. et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016; 127: 1417-1425
    CrossrefPubMedGoogle Scholar
  • 9 Beyer-Westendorf J, Michalski F, Tittl L. et al. Vaginal bleeding and heavy menstrual bleeding during direct oral anti-Xa inhibitor therapy. Thromb Haemost 2016; 115: 1234-1236
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Beyer-Westendorf J, Michalski F, Tittl L. et al. 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 Hematol 2016; 3: e480-e488
    PubMedGoogle Scholar
  • 11 Agnelli G, Buller HR, Cohen A. et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799-808
    CrossrefPubMedGoogle Scholar
  • 12 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihaemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694
    CrossrefPubMedGoogle Scholar
  • 13 Bleker SM, Cohen AT, Buller HR. et al. Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin. Results from the AMPLIFY trial Thromb Haemost 2016; 116: 1159-1164
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Kadir RA, Edlund M, Von Mackensen S. The impact of menstrual disorders on quality of life in women with inherited bleeding disorders. Haemophilia 2010; 16: 832-839
    CrossrefPubMedGoogle Scholar
  • 15 Berntorp E, Follrud C, Lethagen S. No increased risk of venous thrombosis in women taking tranexamic acid. Thromb Haemost 2001; 86: 714-715
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Sundstrom A, Seaman H, Kieler H. et al. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database. Br J Obstet Gynecol 2009; 116: 91-97
    CrossrefPubMedGoogle Scholar
  • 17 Cohen H, Arachchillage DR, Beyer-Westendorf J. et al. Direct Oral Anticoagulants and Women. Semin Thromb Haemost 2016; 42: 789-797
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Vanassche T, Hirsh J, Eikelboom JW. et al. Organ-specific bleeding patterns of anticoagulant therapy: lessons from clinical trials. Thromb Haemost 2014; 112: 918-923
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Desai J, Kolb JM, Weitz JI. et al. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110: 205-212
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Zakherah MS, Sayed GH, El-Nashar SA. et al. Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnostic accuracy compared to alkaline hematin. Gynecol Obstet Invest 2011; 71: 281-284
    CrossrefPubMedGoogle Scholar