Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape

Submitted: 12 January 2024
Accepted: 13 February 2024
Published: 29 February 2024
Abstract Views: 1211
PDF: 199
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Cancer is a leading cause of morbidity and mortality worldwide. It is also one of the strongest risk factors for venous thromboembolism (VTE), reported in approximately 20% of all cases of VTE diagnosed. The thrombotic effect of cancer and its treatments, however, is highly variable among patients and changes over the course of their cancer. Anticoagulant therapy remains the cornerstone of VTE treatment, but it is associated with a substantial rate of VTE recurrence and the potential for serious bleeding. The risk of bleeding in patients with cancer is also dependent on the cancer type and its treatments, often revealing underlying tumor invasion of mucosal or parenchymal tissues, and treatment complications such as thrombocytopenia or coagulopathy. Over the past few decades, efforts to improve the efficacy and safety of anticoagulant therapy for the treatment and prevention of cancer-associated thromboembolism have resulted in changes in the standard of practice. This evolution has been made possible largely through the development of new anticoagulants. This review will reflect on the major advances in the treatment of cancer-associated thrombosis and offer insights on how to address unmet needs in this field.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Ferlay J, Colombet M, Soerjomataram I, Parkin DM, et al. Cancer statistics for the year 2020: an overview. Int J Cancer 2021.
Cohen AT, Katholing A, Rietbrock S, et al. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost 2017;117:57-65.
Mahajan A, Brunson A, Adesina O, et al. The incidence of cancer-associated thrombosis is increasing over time. Blood Adv 2022;6:307-20.
Mulder FI, Horvath-Puho E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021;137:1959-69.
Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009;27:4839-47.
Frere C, Font C, Esposito F, et al. Incidence, risk factors, and management of bleeding in patients receiving anticoagulants for the treatment of cancer-associated thrombosis. Support Care Cancer 2022;30:2919-31.
Hirsh J, Eikelboom JW, Chan NC. Fifty years of research on antithrombotic therapy: achievements and disappointments. Eur J Intern Med 2019;70:1-7.
Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1960;1: 1309-12.
Levine M, Hirsh J. The diagnosis and treatment of thrombosis in the cancer patient. Semin Oncol 1990;17:160-71.
Sutherland DE, Weitz IC, Liebman HA. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol 2003;72:43-52.
Chan A, Woodruff RK. Complications and failure of anticoagulation therapy in the treatment of venous thromboembolism in patients with disseminated malignancy. Aust N Z J Med 1992;22:119-22.
van Dongen CJ, van den Belt AG, Prins MH, Lensing AW. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 2004:CD001100.
Khorana AA, Streiff MB, Farge D, et al. Venous thromboembolism prophylaxis and treatment in cancer: a consensus statement of major guidelines panels and call to action. J Clin Oncol 2009;27:4919-26.
Akl EA, Kahale L, Barba M, et al. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev 2014:CD006650.
Khorana AA, McCrae KR, Milentijevic D, et al. Current practice patterns and patient persistence with anticoagulant treatments for cancer-associated thrombosis. Res Pract Thromb Haemost 2017;1:14-22.
Athanazio RA, Ceresetto JM, Marfil Rivera LJ, et al. direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: a latin american perspective. Clin Appl Thromb Hemost 2022;28:10760296221082988.
Chew TW, Gau CS, Wen YW, et al. Epidemiology, clinical profile and treatment patterns of venous thromboembolism in cancer patients in Taiwan: a population-based study. BMC Cancer 2015;15:298.
Rahme E, Feugere G, Sirois C, et al. Anticoagulant use in patients with cancer associated venous thromboembolism: a retrospective cohort study. Thromb Res 2013;131:210-7.
van Doormaal FF, Raskob GE, Davidson BL, et al. Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials. Thromb Haemost 2009;101:762-9.
Schulman S, Goldhaber SZ, Kearon C, et al. Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer. Thromb Haemost 2015;114:150-7.
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;38:496-520.
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;5:927-74.
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;124:1968-75.
Carrier M, Cameron C, Delluc A, Castellucci L, Khorana AA, Lee AY. Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis. Thromb Res 2014;134: 1214-9.
Rossel A, Robert-Ebadi H, Combescure C, et al. Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: a systematic review and network meta-analysis. PLoS One 2019;14:e0213940.
Carrier M, Blais N, Crowther M, et al. Treatment algorithm in cancer-associated thrombosis: updated Canadian expert consensus. Curr Oncol 2021;28:5434-51.
Frere C, Farge D, Schrag D, et al. Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials. J Hematol Oncol 2022;15:69.
Ageno W, Vedovati MC, Cohen A, et al. Bleeding with apixaban and dalteparin in patients with cancer-associated venous thromboembolism: results from the Caravaggio Study. Thromb Haemost 2021;121:616-24.
Kraaijpoel N, Di Nisio M, Mulder FI, et al. Clinical impact of bleeding in cancer-associated venous thromboembolism: results from the Hokusai VTE cancer study. Thromb Haemost 2018;118:1439-49.
Wang TF, Khorana AA, Agnelli G, et al. Treatment of cancer-associated thrombosis: recent advances, unmet needs, and future direction. Oncologist 2023;28:555-64.
Abdulla A, Davis WM, Ratnaweera N, et al. A meta-analysis of case fatality rates of recurrent venous thromboembolism and major bleeding in patients with cancer. Thromb Haemost 2020;120:702-13.
Weitz JI, Chan NC. Novel antithrombotic strategies for treatment of venous thromboembolism. Blood 2020;135:351-9.
Santagata D, Donadini MP, Ageno W. Factor XI inhibitors for the prevention of cardiovascular disease: a new therapeutic approach on the horizon? Blood Rev 2023;62:101119.
Salomon O, Gailani D. A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors. J Thromb Haemost 2022;20:32-8.
Ray WA, Chung CP, Murray KT, et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA 2018;320:2221-30.
Joseph P, Glynn R, Lonn E, et al. Rosuvastatin for the prevention of venous thromboembolism: a pooled analysis of the HOPE-3 and JUPITER randomized controlled trials. Cardiovasc Res 2022;118:897-903.
Stopa JD, Zwicker JI. The intersection of protein disulfide isomerase and cancer associated thrombosis. Thromb Res 2018;164:S130-S5.
Beckman JD, DaSilva A, Aronovich E, et al. JAK-STAT inhibition reduces endothelial prothrombotic activation and leukocyte-endothelial proadhesive interactions. J Thromb Haemost 2023;21:1366-80.
Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017;130:1499-506.
Carney BJ, Wang TF, Ren S, et al. Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study. Blood Adv 2021;5: 5546-53.
Cohen O, Caiano LM, Levy-Mendelovich S. Cancer-associated splanchnic vein thrombosis: clinical implications and management considerations. Thromb Res 2024;234:75-85.
Sanfilippo KM, Moik F, Candeloro M, et al. Unanswered questions in cancer-associated thrombosis. Br J Haematol 2022;198:812-25.
Yamashita Y, Morimoto T, Muraoka N, et al. Edoxaban for 12 months versus 3 months in patients with cancer with isolated distal deep vein thrombosis (ONCO DVT study): an open-label, multicenter, randomized clinical trial. Circulation 2023;148:1665-76.
Mahe I, Agnelli G, Ay C, et al. extended anticoagulant treatment with full- or reduced-dose apixaban in patients with cancer-associated venous thromboembolism: rationale and design of the API-CAT Study. Thromb Haemost 2022;122:646-56.
Otero R, Solier-Lopez A, Sanchez-Lopez V, et al. Biomarkers of venous thromboembolism recurrence after discontinuation of low molecular weight heparin treatment for cancer-associated thrombosis (HISPALIS-Study). Cancers (Basel) 2022;14.
Schmidt RA, Al Zaki A, Desilet N, et al. Patient characteristics and long-term outcomes beyond the first 6 months after a diagnosis of cancer-associated venous thromboembolism. Thromb Res 2020;188:106-14.
White C, Noble SIR, Watson M, et al. Prevalence, symptom burden, and natural history of deep vein thrombosis in people with advanced cancer in specialist palliative care units (HIDDen): a prospective longitudinal observational study. Lancet Haematol 2019;6:e79-e88.
Candeloro M, Guman NAM, Kraaijpoel N, Di Nisio M. Risk assessment models for thrombosis and anticoagulant related bleeding in ambulatory cancer patients. Semin Thromb Hemost 2021;47:972-81.
Tawil N, Bassawon R, Rak J. Oncogenes and clotting factors: the emerging role of tumor cell genome and epigenome in cancer-associated thrombosis. Semin Thromb Hemost 2019;45:373-84.
Michaels L. Cancer incidence and mortality in patients having anticoagulant therapy. Lancet. 1964;2:832-5.
Zacharski LR, Henderson WG, Rickles FR, et al. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. JAMA 1981;245:831-5.
Smorenburg SM, Vink R, Otten HM, Swaneveld F, Buller HR. The effects of vitamin K-antagonists on survival of patients with malignancy: a systematic analysis. Thromb Haemost 2001;86:1586-7.
Montroy J, Lalu MM, Auer RC, et al. The efficacy and safety of low molecular weight heparin administration to improve survival of cancer patients: a systematic review and meta-analysis. Thromb Haemost 2020;120:832-46.
Mousa SA, Petersen LJ. Anti-cancer properties of low-molecular-weight heparin: preclinical evidence. Thromb Haemost 2009;102:258-67.
Chiasakul T, Zwicker JI. The impact of warfarin on overall survival in cancer patients. Thromb Res 2022;213:S113-S9.
Datta T, Brunson A, Mahajan A, et al. Racial disparities in cancer-associated thrombosis. Blood Adv 2022;6:3167-77.
Wiredu C, Haynes N, Guerra C, Ky B. Racial and ethnic disparities in cancer-associated thrombosis. Thromb Haemost 2022;122:662-5.
da Costa WL, Jr., Guffey D, Oluyomi A, et al. Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations. Am J Hematol 2022;97:1044-54.
Noble S, Prout H, Nelson A. Patients’ experiences of LIving with CANcer-associated thrombosis: the PELICAN study. Patient Prefer Adherence 2015;9:337-45.
Lee LH, Nagarajan C, Tan CW, Ng HJ. Epidemiology of cancer-associated thrombosis in Asia: a systematic review. Front Cardiovasc Med 2021;8:669288.

How to Cite

Lee, A. Y. (2024). Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape. Bleeding, Thrombosis and Vascular Biology, 3(s1). https://doi.org/10.4081/btvb.2024.111