Anticoagulation in Cancer Patients: a Summary of Pitfalls to Avoid
- 128 Downloads
Purpose of Review
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients, and its management is often associated with complications including risk of recurrent VTE and bleeding. Here, we review the current data on pitfalls during anticoagulation in cancer patients and measures necessary to avoid them.
Although low-molecular-weight heparin monotherapy has been the standard of treatment for several years, emerging data for direct oral anticoagulants (DOACs) are leading to new paradigms in treatment. Reports of recent randomized trials suggest a lower risk of recurrent thrombosis but higher risk of bleeding, particularly in gastrointestinal cancer patients, with DOACs. Careful patient selection and individualization of therapy based on risk of bleeding as well as recurrent VTE are keys.
Problems like bleeding, recurrence, thrombocytopenia, drug-drug interactions, renal impairment, nausea-vomiting along with concerns about adherence arise during anticoagulation in cancer patients. However, with adequate pre-treatment assessment, correct anticoagulant selection and proper monitoring during anticoagulation, these issues can be addressed safely and effectively.
KeywordsCancer VTE Thromboembolism Anticoagulation Thromboprophylaxis Pitfalls Bleeding Thrombocytopenia Chemotherapy LMWH VKA DOAC Adherence Renal insufficiency Drug-drug interactions
Compliance with Ethical Standards
Conflict of Interest
Harsh K. Patel declares that he has no conflict of interest.
Alok A. Khorana has received compensation from Bayer, Sanofi, Parexel, Halozyme Therapeutics, Pfizer, Seattle Genetics, Pharmacyclics, PharmaCyte Biotech, AngioDynamics, LEO Pharma, TriSalus, and Medscape/WebMD for service as a consultant; has received travel support from Bayer, Sanofi, Parexel, Janssen, Halozyme Therapeutics, Pfizer, Seattle Genetics, AngioDynamics, LEO Pharma, and Medscape/WebMD; and is the Co-Chair of the CASSINI Steering Committee, as well as the National Coordinator for the MARINER trial, both of which are funded by Janssen.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines)
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Gussoni G, Frasson S, La Regina M, Di Micco P, Monreal M. Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry. Thromb Res. 2013;131(1):24–30. https://doi.org/10.1016/j.thromres.2012.10.007.CrossRefPubMedGoogle Scholar
- 11.Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33(6):654–6. https://doi.org/10.1200/JCO.2014.59.7351.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Farge D, Bounameaux H, Brenner B, Cajfinger F, Debourdeau P, Khorana AA, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):452–66. https://doi.org/10.1016/S1470-2045(16)30369-2.CrossRefGoogle Scholar
- 15.• Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost. 2018;16:1891–4. https://doi.org/10.1111/jth.14219 This guidance document from ISTH emphasizes an individualized approach to choice of anticoagulation in treatment of cancer-associated VTE. CrossRefPubMedGoogle Scholar
- 17.Streiff MB, Milentijevic D, McCrae K, Yannicelli D, Fortier J, Nelson WW, et al. Effectiveness and safety of anticoagulants for the treatment of venous thromboembolism in patients with cancer. Am J Hematol. 2018;93(5):664–71. https://doi.org/10.1002/ajh.25059.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.van der Wall SJ, Klok FA, den Exter PL, Barrios D, Morillo R, Cannegieter SC, et al. Continuation of low-molecular-weight heparin treatment for cancer-related venous thromboembolism: a prospective cohort study in daily clinical practice. J Thromb Haemost. 2017;15(1):74–9. https://doi.org/10.1111/jth.13563.CrossRefPubMedGoogle Scholar
- 23.Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, 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):2017–23. https://doi.org/10.1200/JCO.2018.78.8034.CrossRefPubMedGoogle Scholar
- 24.• Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378(7):615–24. https://doi.org/10.1056/NEJMoa1711948 The study was one of two randomized trials to evaluate the benefit of a DOAC, rivaroxaban, compared to dalteparin monotherapy in treatment. CrossRefPubMedGoogle Scholar
- 25.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;150:86–9. https://doi.org/10.1016/j.thromres.2016.12.016.CrossRefPubMedGoogle Scholar
- 27.Carrier M, Khorana AA, Zwicker JI, Noble S, Lee AYY. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost. 2013;11(9):1760–5. https://doi.org/10.1111/jth.12338.CrossRefPubMedGoogle Scholar
- 30.Carrier M, Cameron C, Delluc A, Castellucci L, Khorana A, Lee AYY. Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis. Thromb Res. 2014;134(6):1214–9. https://doi.org/10.1016/j.thromres.2014.09.039.CrossRefPubMedGoogle Scholar
- 31.Kahale LA, Hakoum MB, Tsolakian IG, et al. Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer (review). Cochrane Database Syst Rev. 2018;6:CD006650. https://doi.org/10.1002/14651858.CD006650.pub5.www.cochranelibrary.com.CrossRefPubMedGoogle Scholar
- 35.Samuelson Bannow BR, Lee AYY, Khorana AA, et al. Management of anticoagulation for cancer-associated thrombosis in patients with thrombocytopenia: a systematic review. Res Pract Thromb Haemost. 2018;(April):1–6. https://doi.org/10.1002/rth2.12111
- 36.• Samuelson Bannow BT, Lee A, Khorana AA, et al. Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost. 2018;16(6):1246–9. https://doi.org/10.1111/jth.14015 This ISTH guidance article provides advice regarding thrombocytopenia in cancer VTE and its effective management. CrossRefPubMedGoogle Scholar
- 39.• Bauersachs R, Lee AYY, Kamphuisen PW, et al. Renal Impairment, recurrent venous thromboembolism and bleeding in cancer patients with acute venous thromboembolism—analysis of the CATCH study. Thromb Haemost. 2018;118(5):914–21. https://doi.org/10.1055/s-0038-1641150 This is one of few articles that focus on the incidence and outcomes of anticoagulating cancer patients with renal insufficiency derived from a large study cohort. CrossRefPubMedGoogle Scholar
- 42.Kooiman J, den Exter PL, Cannegieter SC, le Cessie S, del Toro J, Sahuquillo JC, et al. Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer-associated venous thromboembolism during anticoagulant treatment. J Thromb Haemost. 2013;11(11):1968–76. https://doi.org/10.1111/jth.12411.CrossRefPubMedGoogle Scholar
- 43.Woodruff S, FeugÃ ¨r G, Abreu P, Heissler J, Ruiz MT, Jen F. A post hoc analysis of dalteparin versus oral anticoagulant (VKA) therapy for the prevention of recurrent venous thromboembolism (rVTE) in patients with cancer and renal impairment. J Thromb Thrombolysis. 2016;42(4):494–504. https://doi.org/10.1007/s11239-016-1386-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 46.•• Riess H, Ay C, Bauersachs R, et al. Use of direct oral anticoagulants in patients with cancer: practical considerations for the management of patients with nausea or vomiting. Oncologist. 2018;23(7):822–39. https://doi.org/10.1634/theoncologist.2017-0473 This consensus statement provides information regarding how best to manage DOAC therapy in patients with nausea and emesis. CrossRefPubMedGoogle Scholar
- 48.• 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(1):14–22. https://doi.org/10.1002/rth2.12002 This paper provides clinical practice information regarding persistence with anticoagulant therapy. CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Cajfinger F, Debourdeau P, Lamblin A, Benatar V, Falvo N, Benhamou Y, et al. Low-molecular-weight heparins for cancer-associated thrombosis: adherence to clinical practice guidelines and patient perception in TROPIQUE, a 409-patient prospective observational study. Thromb Res. 2016;144:85–92. https://doi.org/10.1016/j.thromres.2016.06.005.CrossRefPubMedGoogle Scholar
- 51.Sevestre MA, Belizna C, Durant C, Bosson JL, Vedrine L, Cajfinger F, et al. Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: the CARMEN study. J Mal Vasc. 2014;39(3):161–8. https://doi.org/10.1016/j.jmv.2014.03.001.CrossRefPubMedGoogle Scholar
- 52.Noble S, Matzdorff A, Maraveyas A, Pisa G, Pisa G. Assessing patients’ anticoagulation preferences for the treatment of cancer-associated thrombosis using conjoint methodology. Haematologica. 2015;100(11):1486–92. https://doi.org/10.3324/haematol.2015.127126.CrossRefPubMedPubMedCentralGoogle Scholar
- 53.Kaatz S, Fu AC, AbuDagga A, LaMori J, Bookhart BK, Damaraju CV, et al. Association between anticoagulant treatment duration and risk of venous thromboembolism recurrence and bleeding in clinical practice. Thromb Res. 2014;134(4):807–13. https://doi.org/10.1016/j.thromres.2014.07.027.CrossRefPubMedGoogle Scholar
- 56.Spirk D, Ugi J, Korte W, Husmann M, Hayoz D, Baldi T, et al. Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer the SWIss venous ThromboEmbolism registry (SWIVTER) II. Thromb Haemost. 2011;105(6):962–7. https://doi.org/10.1160/TH11-01-0002.CrossRefPubMedGoogle Scholar
- 62.Yano R, Kurokawa T, Tsuyoshi H, et al. Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin. Ann Pharmacother. 2011;45(10). https://doi.org/10.1345/aph.1Q290.