Thromb Haemost 2024; 124(04): 363-373
DOI: 10.1055/a-2191-7510
Stroke, Systemic or Venous Thromboembolism

Enoxaparin for Long-Term Therapy of Venous Thromboembolism in Patients with Cancer and Renal Insufficiency

Patricia Sigüenza
1   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
2   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
1   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
2   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
3   Fundació Institut Germans Trias i Pujol, Badalona, Barcelona, Spain
Conxita Falgá
4   Department of Internal Medicine, Hospital de Mataró, Spain
5   Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
Antoni Riera-Mestre
6   Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL.L'Hospitalet de Llobregat, Universitat de Barcelona, Barcelona, Spain
7   Department of Internal Medicine, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
8   Department of Medical and Surgical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
9   Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium
Ana Cristina Montenegro
10   Department of Vascular Medicine, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia
Cristina Barbagelata
11   Department of Internal Medicine, Hospital Universitario A Coruña, Coruña, Spain
Egidio Imbalzano
12   Division of Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Manuel Monreal
13   Faculty of Health Sciences, Universidad Católica San Antonio de Murcia, CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain
the RIETE Investigators › Author Affiliations


Background The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high risk of bleeding.

Methods We used the Registro Informatizado Enfermedad Tromboemb00F3lica (RIETE) registry to compare the 6-month incidence rates of (1) VTE recurrences versus major bleeding and (2) fatal pulmonary embolism (PE) versus fatal bleeding in three subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy.

Results From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild RI, 1,168 (41%) moderate RI, and 244 (8.6%) had severe RI. Overall, 68, 62, and 12%, respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences versus major bleeding (4.6 vs. 5.4%) and fatal PE versus fatal bleeding (1.3 vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1 vs. 6.3%), but fatal PE and fatal bleeding were close (1.8 vs. 1.2%). Among patients with severe RI, VTE recurrences were threefold less common than major bleeding (4.1 vs. 13%), but fatal PE was threefold more frequent than fatal bleeding (2.5 vs. 0.8%). During the first 10 days, fatal PE was fivefold more common than fatal bleeding (2.1 vs. 0.4%).

Conclusion Among cancer patients with severe RI, fatal PE was fivefold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

* A full list of the RIETE investigators is given in the [appendix].

Supplementary Material

Publication History

Received: 11 August 2023

Accepted: 12 October 2023

Accepted Manuscript online:
13 October 2023

Article published online:
15 November 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease. Chest 2016; 149 (02) 315-352
  • 2 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2020; 38 (05) 496-520
  • 3 Falanga A, Ay C, Di Nisio M. et al; ESMO Guidelines Committee. Electronic address: Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol 2023; 34 (05) 452-467
  • 4 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 2022; 23 (07) e334-e347
  • 5 Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation 2003; 107 (23, Suppl 1): I17-I21
  • 6 Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006; 144 (09) 673-684
  • 7 Buckley MM, Sorkin EM. Enoxaparin. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders. Drugs 1992; 44 (03) 465-497
  • 8 Brophy DF, Sica DA. Use of enoxaparin in patients with chronic kidney disease: safety considerations. Drug Saf 2007; 30 (11) 991-994
  • 9 Annex III: Summary of product characteristics, labelling and package leaflet. Accessed October 27, 2023, at:
  • 10 Bikdeli B, Jiménez D, Hawkins M. et al; RIETE Investigators. Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 2018; 118 (01) 214-224
  • 11 Trujillo-Santos J, Farge-Bancel D, Pedrajas JM. et al; RIETE Investigators. Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: the RIETECAT study. Res Pract Thromb Haemost 2022; 6 (04) e12736
  • 12 Gerlach AT, Pickworth KK, Seth SK, Tanna SB, Barnes JF. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy 2000; 20 (07) 771-775
  • 13 Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8 (01) 202-204
  • 14 Monreal M, Falgá C, Valle R. et al; RIETE Investigators. Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry. Am J Med 2006; 119 (12) 1073-1079
  • 15 Falgá C, Capdevila JA, Soler S. et al. Clinical outcome of patients with venous thrombo-embolism and renal insufficiency. Findings from the RIETE Registry. Thromb Haemost 2007; 98 (04) 771-776
  • 16 Trujillo-Santos J, Schellong S, Falgá C. et al; RIETE Investigators. Low-molecular-weight or unfractionated heparin in venous thromboembolism: the influence of renal function. Am J Med 2013; 126 (05) 425-434.e1
  • 17 Murgier M, Bertoletti L, Darmon M. et al. Frequency and prognostic impact of acute kidney injury in patients with pulmonary embolism. Data from the RIETE Registry. Int J Cardiol 2019; 291: 121-126
  • 18 Catella J, Bertoletti L, Mismetti P. et al; investigators of the RIETE registry. Severe renal impairment and risk of bleeding during anticoagulation for venous thromboembolism. J Thromb Haemost 2020; 18 (07) 1728-1737
  • 19 Chopard R, Jiménez D, Serzian G. et al. Renal dysfunction improves risk stratification and may call for a change in the management of intermediate- and high-risk acute pulmonary embolism: results from a multicenter cohort study with external validation. Crit Care 2021; 25 (01) 57
  • 20 Murgier M, Bertoletti L, Bikdeli B. et al; RIETE Investigators. Prognostic impact of acute kidney injury in patients with acute pulmonary embolism data from the RIETE registry. J Thromb Thrombolysis 2022; 54 (01) 58-66
  • 21 Trujillo-Santos J, Bergmann JF, Bortoluzzi C. et al; RIETE Investigators. Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism. J Thromb Haemost 2017; 15 (03) 429-438
  • 22 Thorevska N, Amoateng-Adjepong Y, Sabahi R. et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004; 125 (03) 856-863