Background Patients with limited prognosis (expected to die within ~6 months) often have co-morbidities requiring the use of anticoagulation (AC), including atrial fibrillation (AF), history of embolic stroke, and venous thromboembolic (VTE) disease (1-3). Several studies have shown that the incidence of thromboembolism in these patients is as high as 50%. At the same time, most of these patients are also at high risk for bleeding complications (2). To date, there are no consensus guidelines regarding when AC should be continued or discontinued in patients with limited prognosis (4-6). This critical decision remains challenging for providers seeking to optimize the quality of life (QoL) of patients since they must weigh the potential catastrophic complications associated with bleeding versus those associated with new thromboembolic events (7). This Fast Fact discusses factors informing the use of AC in these patients. AC for valvular disease has many unique considerations and is not discussed here.
- In patients with a limited prognosis, especially when the focus is on optimizing QoL, the continued use of AC should be reassessed since the risk-benefit ratio of clotting to bleeding has likely changed (4,8,9). Moreover, continued use of AC may lead to unexpected bleeding events, which must be weighed against the risk of impaired QoL from new thromboembolic events, the burden of drug administration, drug cost, ease of monitoring, and the patient’s overall prognosis, values, and preferences (8,10).
- Patients with shorter prognoses often have risk factors for VTEs and strokes, including prolonged immobilization, recent major surgery, cancer, and heart failure. However, the true impact of VTEs and strokes on the morbidity and mortality of patients reaching the end of their lives is not fully understood due to the lack of clinical studies in this population (11,12).
- In addition to these risk factors, patients with limited prognosis are also at high risk of bleeding due to altered anticoagulant pharmacokinetics secondary to malnutrition and poor oral intake (13), extremes of body weight (13), thrombocytopenia (14), renal insufficiency (13), hepatic impairment (15), advanced age (15), and drug-drug and drug-disease interactions (15). Notably, though, studies suggest the benefit of AC largely outweighs the risk of fall-related bleeding; but the risk-benefit ratio is largely unknown in those with limited prognosis (16,17).
- Due to the inability to measure long-term outcomes in patients with a limited prognosis, there are minimal clinical data describing the efficacy of AC in this patient population. However, the usage of risk-scoring tools enables shared decision-making by weighing the risks and benefits of AC in different contexts. There are multiple different risk scoring tools available; examples are included in Table 1. Please also see Table 2 for drug options for anticoagulation.
|Table 1: Considerations for Continuing or Discontinuing AC at the end of life (18-23)|
|Disease||Risk scores for stroke or VTEs||Risk scores for bleeding||High-risk patients for stroke or VTEs||High-risk patients for bleeding|
|AF||CHA2DS2– VASc (18)||HAS-BLED, HEMORR2HAGES, ATRIA, ORBIT (18,19)||If CHA2DS2-VASc > HAS-BLED or CHA2DS2-VASc >7 and HAS-BLED <3: Consider continuing AC.||If CHA2DS2-VASc < HAS-BLED or CHA2DS2-VASc ≤7 and HAS-BLED score ≥3: Consider stopping AC.|
|Cancer||Khorana score CATSSCORE, PROTECHT (21,22)||CAT-BLEED, ACCP VTE, EINSTEIN, HAS-BLED, VTE BLEED (23)||If Khorana > CATBLEED or Patient has gastric or pancreatic cancer and CATBLEED < 14.2%: Consider continuing AC||If Khorana < CAT-BLEED or CAT-BLEED is ≥ 14.2%: Consider stopping AC|
|Both||In patients with significant nutritional impairments, impaired swallowing, and prognosis in the range of days to weeks (most patients who enroll in hospice care in the US), discontinuing AC given the low absolute risk of VTE should be strongly considered (5,13).|
|Table 2: Drug Options and Considerations|
|Drug Name||Indications||Considerations/Approximate Cost in 2023 USD (15,24)|
|Warfarin||Non-valvular AF, DVT, PE||Inexpensive ($3/month) but often avoided, especially in the elderly, unless alternative options are contraindicated or cost prohibitive. Reasons to avoid include increased risk of bleeding compared to DOACs, drug monitoring burden, dietary restrictions, and drug-disease and drug-drug interactions.|
|Low molecular weight heparin (LMWH)||DVT, PE||Expensive ($600/month), subcutaneous (SC) route, bruising/bleeding associated with injections, patient administration education needed.|
|Unfractionated heparin (UFH)||Non-valvular AF, DVT, PE||Expensive (~$450/month), SC UFH can be an alternative in patients unable or unwilling to take LMWH, Warfarin, or DOACs. However, long-term anticoagulation with UFH has been inadequately studied, and thus not currently recommended (24).|
|Direct oral anticoagulants (DOAC)||Non-valvular AF, DVT, PE||Expensive ($300-460/month). Apixaban generally preferred due to lower bleeding risk & better safety data in chronic kidney disease. Dabigatran and edoxaban should be avoided in obese patients (>120 kg, BMI > 40). Rivaroxaban probably has the highest bleeding risk.|
Bottom line The decision to continue or discontinue AC should be individualized with shared decision-making. Risk calculators can provide data to help clinicians and patients in making decisions.
Resources: CHA2DS2-VASc Calculator, HAS-BLEDCalculator, HEMORR2HAGESCalculator, ATRIACalculator, ORBITCalculator, Khorana Score Calculator, CATSSCORECalculator, PROTECHT Score, ACCP VTE Score, EINSTEINScore, VTE BLEED Score, CAT-BLEED Score
1. Kim J, Parish AL. Polypharmacy and medication management in older adults. Nurs Clin North Am. Sep 2017;52(3):457-468. doi:10.1016/j.cnur.2017.04.007
2. Johnson MJ, McMillan B, Fairhurst C, et al. Primary thromboprophylaxis in hospices: the association between risk of venous thromboembolism and development of symptoms. J Pain Symptom Manage. Jul 2014;48(1):56-64. doi:10.1016/j.jpainsymman.2013.08.016
3. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. Feb 2012;141(2 Suppl):e152S-e184S. doi:10.1378/chest.11-2295
4. Huisman BAA, Geijteman ECT, Kolf N, et al. Physicians’ opinions on anticoagulant therapy in patients with a limited life expectancy. Semin Thromb Hemost. Sep 2021;47(6):735-744. doi:10.1055/s-0041-1725115
5. Kowalewska CA, Noble BN, Fromme EK, McPherson ML, Grace KN, Furuno JP. Prevalence and clinical intentions of antithrombotic therapy on discharge to hospice care. J Palliat Med. Nov 2017;20(11):1225-1230. doi:10.1089/jpm.2016.0487
6. Ouellet GM, Fried TR, Gilstrap LG, et al. Anticoagulant use for atrial fibrillation among persons with advanced dementia at the end of life. JAMA Internal Medicine. 2021;181(8):1121-1123. doi:10.1001/jamainternmed.2021.1819
7. Ko D, Lin KJ, Bessette LG, et al. Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020. JAMA Netw Open. 2022;5(11):e2242964. doi:10.1001/jamanetworkopen.2022.42964
8. Huisman BAA, Geijteman ECT, Arevalo JJ, et al. Use of antithrombotics at the end of life: an in-depth chart review study. BMC Palliat Care. 2021/07/16 2021;20(1):110. doi:10.1186/s12904-021-00786-3
9. Proietti M, Camera M, Gallieni M, et al. Use and prescription of direct oral anticoagulants in older and frail patients with atrial fibrillation: a multidisciplinary consensus document. J Pers Med. Mar 15 2022;12(3)doi:10.3390/jpm12030469
10. Zabrocka E, Sierko E. Thromboprophylaxis in the end-of-life cancer care: the update. Cancers (Basel). Mar 5 2020;12(3)doi:10.3390/cancers12030600
11. Anderson FA, Spencer FA. Risk Factors for Venous Thromboembolism. Circulation. 2003;107(23_suppl_1). doi:10.1161/01.CIR.0000078469.07362.E6
12. Chin-Yee N, Tanuseputro P, Carrier M, Noble S. Thromboembolic disease in palliative and end-of-life care: A narrative review. Thromb Res. 2019;175:84-89. doi:10.1016/j.thromres.2018.12.028
13. Holmes HM, Bain KT, Zalpour A, Luo R, Bruera E, Goodwin JS. Predictors of anticoagulation in hospice patients with lung cancer. Cancer. Oct 15 2010;116(20):4817-24. doi:10.1002/cncr.25284
14. Gillon S, Noble S, Ward J, et al. Primary thromboprophylaxis for hospice inpatients: who needs it? Palliat Med. 2011;25(7):701-705.
15. Chen A, Stecker E, Warden BA. Direct oral anticoagulant use: a practical guide to common clinical challenges. Journal of the American Heart Association. 2020;9(13):e017559. doi:doi:10.1161/JAHA.120.017559
16. Hagerty, T, Rich, MW. Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance. Cleve Clin J Med. Jan 2017;84(1):35-40; DOI: 10.3949/ccjm.84a.16016
17. Shanah L, Kabashneh S, Alkassis S, Ali H, Mir T. Use of Anticoagulants in Patients With Non-Valvular Atrial Fibrillation Who Are at Risk of Falls. Cureus. 2020 Sep 9;12(9):e10336. doi: 10.7759/cureus.10336. PMID: 33052296; PMCID: PMC7546592.
18. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. Feb 1 2021;42(5):373-498. doi:10.1093/eurheartj/ehaa612
19. Gao X, Cai X, Yang Y, Zhou Y, Zhu W. Diagnostic Accuracy of the HAS-BLED Bleeding Score in VKA- or DOAC-Treated Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Systematic Review. Frontiers in Cardiovascular Medicine. 2021-November-22 2021;8doi:10.3389/fcvm.2021.757087
20. Lindsay J, Dooley M, Martin J, et al. The development and evaluation of an oncological palliative care deprescribing guideline: the ‘OncPal deprescribing guideline’. Support Care Cancer. 2015;23(1):71-78.
21. Bao Y, Wan X, Fu J, Wu B. The risk of venous thromboembolism in cancer patients receiving chemotherapy: a meta-analysis with systematic review. Ann Transl Med. Feb 2021;9(4):277. doi:10.21037/atm-20-3292
22. Moik F, Englisch C, Pabinger I, Ay C. Risk assessment models of cancer-associated thrombosis – Potentials and perspectives. Thrombosis Update. 2021/12/01/ 2021;5:100075. doi:https://doi.org/10.1016/j.tru.2021.100075
23. de Winter MA, Dorresteijn JAN, Ageno W, et al. Estimating bleeding risk in patients with cancer-associated thrombosis: evaluation of existing risk scores and development of a new risk score. Thromb Haemost. May 2022;122(5):818-829. doi:10.1055/s-0041-1735251
24. Prandoni P, Carnovali M, Marchiori A; Galilei Investigators. Subcutaneous Adjusted-Dose Unfractionated Heparin vs Fixed-Dose Low-Molecular-Weight Heparin in the Initial Treatment of Venous Thromboembolism. Arch Intern Med. 2004 May 24;164(10):1077-83. doi: 10.1001/archinte.164.10.1077.
Version History: originally edited by Drew A Rosielle MD, first electronically published in April 2023
Authors’ Affiliations: Wake Forest School of Medicine (RH, JB, JG), West Virginia University School of Medicine (ES), and Duke University School of Medicine (MH).
Conflicts of Interest: Dr. Gabbard is supported by the National Institute on Aging of the National Institutes of Health under Award Number K23AG070234. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know!
Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.