Download PDF
CC BY 4.0 · TH Open 2024; 08(01): e132-e140
DOI: 10.1055/s-0044-1782219
Original Article

Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry

Zygimantas Zaboras 
1   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
,
Camilla Tøvik Jørgensen
1   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
2   Department of Emergency Medicine, Østfold Hospital, Sarpsborg, Norway
,
Andreas Stensvold
3   Department of Oncology, Østfold Hospital, Sarpsborg, Norway
,
Heidi Hassel Pettersen
4   Department of Research, Østfold Hospital, Sarpsborg, Norway
,
Aleksandra Galovic Grdinic
5   Clinic of Internal Medicine, Østfold Hospital, Sarpsborg, Norway
,
Sigrid Kufaas Brækkan
6   Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
7   Department of Clinical Medicine, Thrombosis Research Group (TREC), UiT – The Arctic University of Norway, Tromsø, Norway
,
Waleed Ghanima
4   Department of Research, Østfold Hospital, Sarpsborg, Norway
5   Clinic of Internal Medicine, Østfold Hospital, Sarpsborg, Norway
8   Department of Hematology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
,
Mazdak Tavoly
4   Department of Research, Østfold Hospital, Sarpsborg, Norway
9   Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
› Author Affiliations Funding None.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce.

Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events.

Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous Thrombosis Registry in ØstfOLd HospitaL. Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment.

Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61–77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2–9.2) and 10.1 (95% CI 8.0–12.9) in CRNMB.

Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Keywords

cancer-associated thrombosis - venous thromboembolism - bleeding - anticoagulants - direct oral anticoagulants - low molecular weight heparin

Authors' Contributions

Z.Z. and W.G. planned the study. Z.Z. drafted the first version of the manuscript. Z.Z. performed and interpreted all statistical analyses with assistance from C.T.J. and S.K.B. W.G., M.T., C.T.J., and S.K.B. critically revised the content. All authors were responsible for carefully reading and approving the final draft of the manuscript.


Data Availability Statement

The data that support the findings of this study is available upon reasonable request from the corresponding author (Z.Z.).


Supplementary Material



Publication History

Received: 20 November 2023

Accepted: 05 February 2024

Article published online:
26 March 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Mulder FI, Horváth-Puhó E, van Es N. et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021; 137 (14) 1959-1969
    CrossrefPubMedGoogle Scholar
  • 2 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
    CrossrefPubMedGoogle Scholar
  • 3 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 5 (03) 632-634
    CrossrefPubMedGoogle Scholar
  • 4 Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thromb Res 2018; 164 (Suppl. 01) S112-S118
    CrossrefPubMedGoogle Scholar
  • 5 Sharman Moser S, Spectre G, Raanani P. et al. Cancer-associated venous thromboembolism in Israel: Incidence, risk factors, treatment, and health care utilization in a population based cohort study. Res Pract Thromb Haemost 2022; 6 (04) e12653-e12653
    CrossrefPubMedGoogle Scholar
  • 6 Prandoni P, Lensing AWA, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
    CrossrefPubMedGoogle Scholar
  • 7 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 6 (06) 401-410
    CrossrefPubMedGoogle Scholar
  • 8 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
  • 9 McBane II RD, Wysokinski WE, Le-Rademacher JG. et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost 2020; 18 (02) 411-421
    CrossrefPubMedGoogle Scholar
  • 10 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
  • 11 Raskob GE, van Es N, Verhamme P. et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
    CrossrefPubMedGoogle Scholar
  • 12 Lyman GH, Carrier M, Ay C. et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5 (04) 927-974
    CrossrefPubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 Streiff MB, Holmstrom B, Angelini D. et al. Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19 (10) 1181-1201
    PubMedGoogle Scholar
  • 15 Khorana AA, Noble S, Lee AYY. et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (09) 1891-1894
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Jørgensen CT, Tavoly M, Pettersen HH. et al. The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description. Res Pract Thromb Haemost 2022; 6 (05) E12770
    CrossrefPubMedGoogle Scholar
  • 18 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
    CrossrefPubMedGoogle Scholar
  • 19 Schulman S, Kearon C. 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 non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 20 Stępień K, Nowak K, Zalewski J, Undas A. Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and colorectal cancer: a single–center experience. Kardiol Pol 2019; 77 (12) 1186-1189
    CrossrefPubMedGoogle Scholar
  • 21 Bertoletti L, Gusto G, Khachatryan A. et al. Anticoagulant treatment patterns and outcomes in patients with venous thromboembolism and active cancer - a nationwide cohort study in France. Blood 2021; 138 (Suppl. 01) 670-670
    CrossrefPubMedGoogle Scholar
  • 22 Uppuluri EM, Burke KR, Haaf CM, Shapiro NL. Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants. J Oncol Pharm Pract 2019; 25 (02) 261-268
    CrossrefPubMedGoogle Scholar
  • 23 Kim S-A, Lee JH, Lee JY. et al. Treatment and bleeding complications of cancer-associated venous thromboembolism: a Korean population-based study. Thromb Haemost 2022; 122 (12) 2011-2018
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Phelps MK, Wiczer TE, Erdeljac HP. et al. A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - a real world experience. J Oncol Pharm Pract 2019; 25 (04) 793-800
    CrossrefPubMedGoogle Scholar
  • 25 Weitz JI, Haas S, Ageno W. et al; GARFIELD-VTE investigators. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE. J Thromb Thrombolysis 2020; 50 (02) 267-277
    CrossrefPubMedGoogle Scholar
  • 26 Stepien K, Nowak K, Zalewski J, Pac A, Undas A. Extended treatment with non-vitamin K antagonist oral anticoagulants versus low-molecular-weight heparins in cancer patients following venous thromboembolism. A pilot study. Vascul Pharmacol 2019; 120: 106567-106567
    CrossrefPubMedGoogle Scholar
  • 27 Moik F, Colling M, Mahé I, Jara-Palomares L, Pabinger I, Ay C. Extended anticoagulation treatment for cancer-associated thrombosis-Rates of recurrence and bleeding beyond 6 months: a systematic review. J Thromb Haemost 2022; 20 (03) 619-634
    CrossrefPubMedGoogle Scholar
  • 28 Yamashita Y, Morimoto T, Amano H. et al; COMMAND VTE Registry Investigators. Anticoagulation therapy for venous thromboembolism in the real world-from the COMMAND VTE Registry. Circ J 2018; 82 (05) 1262-1270
    CrossrefPubMedGoogle Scholar
  • 29 Ross JA, Miller MM, Rojas Hernandez CM. Comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus conventional anticoagulation for the treatment of cancer-related venous thromboembolism: a retrospective analysis. Thromb Res 2017; 150: 86-89
    CrossrefPubMedGoogle Scholar
  • 30 Awano N, Okano T, Kawachi R. et al. One-year incidences of venous thromboembolism, bleeding, and death in patients with lung cancer (Cancer-VTE Subanalysis). JTO Clin Res Rep 2022; 3 (09) 100392
    PubMedGoogle Scholar