In his talk “Management of Blood Clots in Palliative Cancer Patients,” delivered within the context of the ICTHIC webinar titled “Challenges in the management of fragile CAT patients (older patient population & palliative care),” professor Jay Easaw aimed to achieve four goals: explain the importance of managing blood clots, discuss the challenges of managing patients with venous thromboembolism (VTE) in the palliative care setting, explore the role of thromboprophylaxis in palliative patients, and compare the treatments of VTE (DOAC vs. LMWHs) in palliative patients.
You can also watch Jay Easaw’s lecture in the video below and the full webinar recording here.
VTE in cancer patients
VTE is a condition characterized by the formation of blood clots in the veins, typically occurring in the deep veins of the legs (DVT) or as a pulmonary embolism when the clot travels to the lungs. DVT refers specifically to the formation of blood clots in the deep veins, often in the lower limbs. These clots can obstruct blood flow and cause symptoms such as pain, swelling, and redness in the affected area. If left untreated, DVT can lead to serious complications, including pulmonary embolism [1]. As reported in the article by Khorana and colleagues, VTE is more frequently observed in cancer patients when compared to individuals without cancer [2]. Furthermore, cancer patients who develop VTE have poorer outcomes and experience higher mortality rates compared to cancer patients who do not develop VTE [3].
The challenges of managing (VTE) in the palliative care setting
Palliative care is a specialized form of medical care that focuses on enhancing patients’ quality of life and alleviating their suffering [4]. The scope of palliative care extends from providing palliative chemotherapy for patients with incurable stage IV cancer to offering support for patients nearing the end of life.
“The challenge that we experience in palliative care patients is quite significant when it comes to trying to prevent and treat blood clots,” – said Professor Easaw. The optimal use of anticoagulants in palliative care settings has limited evidence [5], primarily due to the challenges associated with studying VTE in this population. Clinical trials often struggle to recruit a sufficient number of participants to achieve statistical power, resulting in contradictory findings across studies. Furthermore, supporting studies tend to exclude patients with poor performance status or a life expectancy of less than three months. Finally, there is a limited understanding of how anticoagulants function in patients nearing the end of life, where the risks of bleeding and recurrent thrombosis are known to be elevated [6].
To prevent and treat VTE, anticoagulant medications are commonly used. From Professor Easaw’s speech, it can be inferred that for patients diagnosed with VTE, low molecular weight heparin (LMWH) is the preferred treatment option due to its lower recurrence rates during treatment. Direct oral anticoagulants (DOACs) have not yet been established as effective or safe in oncology patients and are currently not recommended for managing cancer-associated thrombosis. Warfarin, although less favored, can be considered in situations where LMWH is contraindicated.
The role of thromboprophylaxis in palliative patients
The issue of the utility of thromboprophylaxis in patients undergoing palliative care was addressed in the study conducted by White and colleagues [7], in which the incidence of DVT in 273 cancer patients admitted to a Specialized Palliative Care Unit (SPCU) was evaluated, and no significant relationship between thromboprophylaxis and the development of DVT was found. According to the recommendations from the U.K. National Institute for Health and Care Excellence (NICE), thromboprophylaxis should be taken into consideration for patients admitted to SPCUs who have temporary risk factors for thrombosis. However, NICE advises against administering thromboprophylaxis to patients admitted specifically for end-of-life care [8].
VTE Treatment in palliative cancer patient
To discuss the treatment of VTE, professor Easaw presented the example of a 73-year-old male with metastatic gastric cancer diagnosed with a symptomatic DVT in hospice. Regarding this patient, two questions need to be addressed: 1) Should he be treated? 2) If so, what is the most appropriate treatment?
The potential options provided by the professor are as follows: LMWH (e.g., dalteparin, enoxaparin, tinzaparin), DOAC (e.g., apixaban, edoxaban, rivaroxaban), IVC filter and observation.
Although there are studies comparing LMWH and DOAC in cancer patients, there is limited data available regarding the use of these drugs in palliative care, further exacerbated by the lack of animal studies in this context. LMWHs reduce both the formation of blood clots and bleeding in cancer patients. Three studies conducted on non-palliative cancer patients compared the efficacy of DOACs with that of LMWHs and found no statistically significant differences. However, these studies discouraged the use of DOACs in patients with gastric cancer [9-11]. The explanation lies in the fact that DOACs require absorption in the gastric tract, in the stomach or in the distal small bowel or ascending colon. Also, DOACs require a functional liver, so they are not recommended for patients with hepatic impairment [12]. Another complication in the use of anticoagulants in cancer patients is their potential interaction with chemotherapy agents (this aspect is further discussed in professor McFarlane’s talk).
Conclusion
In conclusion, both LMWH and DOACs can be used in the treatment of VTE in cancer patients. LMWH is easier to prescribe, but some patients may have reservations about receiving injections. On the other hand, DOACs require close monitoring. When it comes to the question of whether to treat VTE in palliative patients or not, there is no straightforward answer. The decision to treat or not to treat a patient in palliative care requires the evaluation of the specific situation of the patient.
References
- Stone, J., et al., Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther, 2017. 7(Suppl 3): p. S276-s284.
- Khorana, A.A., N. Mackman, and A. Falanga, Cancer-associated venous thromboembolism. 2022. 8(1): p. 11.
- Timp, J.F., et al., Epidemiology of cancer-associated venous thrombosis. Blood, 2013. 122(10): p. 1712-23.
- Sepúlveda, C., et al., Palliative Care: the World Health Organization’s global perspective. J Pain Symptom Manage, 2002. 24(2): p. 91-6.
- Cai, R., et al., Thromboprophylaxis for inpatients with advanced cancer in palliative care settings: A systematic review and narrative synthesis. Palliative Medicine, 2019. 33(5): p. 486-499.
- Noble, S., S. Banerjee, and N.J. Pease, Management of venous thromboembolism in far-advanced cancer: current practice. 2022. 12(e6): p. e834-e837.
- White, C., 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. The Lancet Haematology, 2019. 6(2): p. e79-e88.
- Noble, S., Venous thromboembolism in palliative care patients: what do we know? Thromb Res, 2020. 191 Suppl 1: p. S128-s132.
- Raskob, G.E., et al., Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med, 2018. 378(7): p. 615-624.
- Young, A.M., 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): p. 2017-2023.
- Agnelli, G., et al., Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med, 2020. 382(17): p. 1599-1607.
- Qamar, A., et al., Oral Anticoagulation in Patients With Liver Disease. J Am Coll Cardiol, 2018. 71(19): p. 2162-2175.