Background for Fast Fact #236     Venous thromboembolism (VTE) is a common complication of malignancy and has been associated with a poor prognosis (1). As the disease trajectory for cancer continues to evolve, there are nuances in the approach to VTE treatment for this subset of patients (2). This Fast Fact provides a primer to the approach to VTE in patients with serious illness, particularly those with advanced cancer.

Does anticoagulation for VTE improve outcomes? There is little randomized, placebo-controlled data on anticoagulation (AC) for the treatment of VTE (3). The only study comparing heparin and warfarin for acute pulmonary embolism (PE) versus no treatment found a decrease in mortality with a number needed to treat (NNT) of four (4).  Data from non-placebo-controlled trials show that AC for acute VTE decreases recurrence (5) and clot propagation (6).  Based on this evidence and clinical consensus, AC is recommended to decrease mortality and VTE recurrence in patients with a new VTE.

What is the best treatment for VTE for cancer patients? There are multiple types of AC medications.  The decision of which AC to choose is patient-specific and usually made by the oncologist or hematologist and a pharmacist. Broadly, current evidence-based guidelines recommend (7,8):

Does the evidence support AC for VTE in cancer patients with short prognoses? Despite advancements in VTE treatment, most studies exclude patients with an increased creatinine, a poor functional status, and a prognosis less than 3 months (see Fast Fact #13). Thus, there is little data to guide VTE care for patients with cancer in their final weeks to months of life (2). Clinicians must weigh the potential for symptom relief with adverse events such as bleeding that can be distressing to patients and families and the patient’s goals of care. A review of deceased patients with cancer associated thrombosis suggested the risk of bleeding to be significant as death approaches (9).  Furthermore, AC does not immediately lead to VTE resolution, a process that takes 3-6 months in patients with cancer.

Other considerations in the decision to treat acute VTE in cancer patients with short prognoses:       

1. The decision of whether to treat with AC or just treat symptomatically (no AC) is largely empiric and should be based on clinical judgment about prognosis, symptom burden, and patient preference.  For instance, for a patient with a prior history of VTE who remains ambulatory and who develops symptomatic VTE (e.g. a painful, swollen leg), providing AC may prevent symptomatic progression. If this same patient was already bedbound with a prognosis of weeks, it is doubtful AC would provide substantial benefit. Though current evidence-based guidelines recommend AC for incidental VTE in advanced cancer (6), there is no strong rationale for this recommendation when a patient has a prognosis of weeks and the patient’s primary goal of treatment is comfort.
2. If AC is chosen, then collaborate with the patient’s oncologist or hematologist and a clinical pharmacist to select the best agent and dose for that individual patient. In general, LWMH and DOACs do not require routine laboratory testing, have fewer drug-drug interactions, and are less diet dependent than warfarin, so they are usually preferred. LMWH and DOACs are more costly though than warfarin and may be more challenging for hospice agencies to cover.  For example, the cost of DOACs can range from $20-35/day; generic enoxaparin (a LMWH) costs approximately $13/day.  Warfarin by comparison costs only $0.35/day (however this does not include the cost of monitoring).
3. For patients who are on warfarin and suffer a catastrophic bleed, Vitamin K can provide an effective antidote. However, additional supportive treatments such as transfusion are often limited to acute care settings, as are any (expensive) antidotes for DOACs (10). See Fast Fact #41.

Bottom Line     The patient’s prognosis and preferences must be considered prior to starting anticoagulation therapy.  Clinicians should work with hospice agencies to determine an affordable plan to safely administer and monitor anticoagulation for acute VTE in hospice patients.  Clinicians should prepare patients who decide to initiate anticoagulation for discontinuing it once expected survival is short or worsening risks such as bleeding become apparent.

References 

1. Sorensen HT, Mellemkjoer L, Olsen JH and Baron JA.  Prognosis of cancers associated with venous thromboembolism.  N Eng J Med. 2000; 343(25):1846-1850.
2. Chin-Yee N, Tanuseputro P, Carrier M, Noble S.  Thromboembolic disease and end-of-life care: A narrative review.  Thrombosis Research.  175 (2019) 84-89.
3. McManus RJ, Fitzmaurice D, Murray ET and Taylor C. Thromboembolism. Clinical Evidence. 2009; 3(208). Retrieved Oct 8, 2009 from http://clinicalevidence.bmj.com/ceweb/conditions/cvd/0208/0208.jsp.
4. Barritt DW and Jordan SC.  Anticoagulant drugs in the treatment of pulmonary embolism:  a controlled trial. Lancet. 1960; 1:1309-1312.
5. Brandjes DP, Heijboer H, Büller HR, de Rijk M, Jagt H, ten Cate JW.  Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal vein thrombosis.  N Engl J Med. 1992; 327(21):1485-1489.
6. Belcaro G, Laurora G, Cesarone MR et al.  Prevention of the extension of distal deep venous thrombosis:  A randomized controlled trial with a 6 month follow up.  Minerva Med. 1997; 88(12):507-514.
7. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Guideline Update J Clin Onc 2023;41 (16) 3063-3071.
8. Kahale LA, Hakoum MB, Tsolakian IG et al.  Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer.  Cochrane Database Syst Rev. 2018; issue 66 CD006650.
9. Noble S, Banerjee S, Pease NJ.  Management of venous thromboembolism in far-advanced cancer: current practice.  BMJ Supportive & Palliative Care 2022;12:e834-837.
10. Levy JH, et al.  Reversal of direct oral anticoagulants: guidance from the SSC of the International Society on Thrombosis and Haemostasis.  Journal of Thrombosis and Haemostasis.  2024;22:2889-2899.

Author Affiliations:  University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History: Originally published December 2010; Copy-re-edited August 2015 by Sean Marks MD; reviewed and updated again by Heidi Ludtke MD in July 2025 whose content additions were significant enough to warrant being included as a coauthor.