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.

Considerations  

• 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

References

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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.