Venous thromboembolism (VTE) may include a deep vein thrombosis (DVT) or a pulmonary embolism (PE). The incidence of VTEs in terminal phase palliative care patients is often difficult to determine, which may be because the focus in this setting is symptom management rather than diagnosis and undertaking further investigations – also noting that subclinical VTEs may be asymptomatic. The forms of VTE prophylaxis available include compression stockings (such as TEDS), unfractionated heparin, or low molecular weight heparin such as enoxaparin. There is limited evidence for the role of compression stockings in terminal phase palliative care patients. If pharmacological VTE prophylaxis was indicated, enoxaparin may be preferred to unfractionated heparin due to its once-daily dosing (compared to bd-tds with unfractionated heparin). The decision to use VTE prophylaxis in a palliative care patient is a difficult one in that many patients are at greater risk of thrombosis, as well as at a greater risk of bleeding.
In terms of risk factors to consider for thrombosis:
- If patients have cancer, the metastatic cancer itself is a risk factor for thrombosis, noting that the type of cancer is relevant – some types of primary cancers have a higher risk of thrombosis such as lung, pancreatic or haematological cancers, whereas other cancers such as prostate cancer may have a lower risk
- Dehydration (particularly as patients approach the terminal phase and oral intake decreases)
- Age > 60
- Reduced mobility (which will continue to reduce further in the terminal phase)
- If there is concurrent infection
In terms of risk factors to consider for bleeding:
- Active bleeding would be a contraindication. Platelet levels should be considered, for example, a decrease of 30-50% of the initial platelet count, or platelets < 50 x 109/L may be a contraindication to VTE prophylaxis. Consideration of the possibility of heparin-induced thrombocytopenia as an adverse effect should also be considered.
- Significant liver impairment – also consider factors such as previous/current alcohol abuse
- Significant renal impairment – if VTE prophylaxis is indicated, a dose reduction would be appropriate (e.g. enoxaparin 20mg daily for creatinine clearance < 30mL/minute)
- Severe malnutrition may increase bleeding risk. For patients with low body weight (males < 57kg and females < 45kg), guidelines suggest to reduce the dose of enoxaparin to 20mg daily (if VTE prophylaxis is indicated)
- Anaemia (common in palliative care patients) may increase bleeding risk
- A recent study by Tardy et al looked at the bleeding risk of hospice patients (the majority of whom had metastatic cancer) and found that while the incidence of VTEs was low, there was quite a high incidence of significant bleeding in this patient group (9.8%), and it was identified that bleeding was associated with VTE prophylaxis (p=0.04, HR = 1.48 (1.02-2.15))
One of the main goals of palliative care therapy is improving symptoms as well as quality of life for patients. It is noted that the conditions resulting from a thrombotic event may cause unpleasant or distressing symptoms for patients such as painful swollen legs (DVT) or tachycardia/dyspnoea (PE). In addition, if it is a thrombotic event that ends up causing a patient’s death, these distressing symptoms may be present for a number of hours prior to death. However, it is also noted that end-of-life medications may be used for the management of such symptoms (e.g. morphine for dyspnoea or pain), in the event that this does occur. This is in contrast to if a patient experienced a catastrophic haemorrhage as a result of VTE prophylaxis therapy, which may be equally (or more) distressing for patients and there are no medications appropriate to provide ‘symptom relief’. Another consideration in terms of quality of life is that patients may find the daily subcutaneous enoxaparin injection uncomfortable or painful, or they may simply prefer to minimise their medication burden at the end stage of life.
The prognosis or trajectory of a palliative care patient should be considered in the prescribing of VTE prophylaxis (for example, if they have days versus weeks or months to live). The risks versus benefits of using VTE prophylaxis, as well as not using VTE prophylaxis, should be explained to the patient and ultimately their preferences will guide the decision making. Ideally, patients would have considered their preferences for VTE prophylaxis ahead of time, and have this documented on their advanced health directive, however, this would often not be the case. If the patient’s preference was to have VTE prophylaxis, this decision should be re-assessed regularly during their hospital/hospice admission, particularly if their clinical state changes with regards to the factors discussed above.
- Clexane and Clexane Forte (Enoxaparin Sodium) Australian approved product information. Macquarie Park: Sanofi-aventis. Approved August 2020.
- Fernandes CJ, Morinaga LTK, Alves JL Jr, Castro MA, Calderaro D, Jardim CVP et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev. 2019; 28(151):pii:180119.
- Gade IL, Braekkan SK, Naess IA, Hansen JB, Cannegieter SC, Overvad K et al. The impact of initial cancer stage on the incidence of venous thromboembolism: the Scandinavian Thrombosis and Cancer (STAC) Cohort. J Thromb Haemost. 2017; 15(8): 1567-75.
- Hedman C, Frisk G, Björkhem-Bergman L. Deprescribing in Palliative Cancer Care. Life 2022; 12(5): 613.
- Huisman BAA, Geijteman ECT, Arevalo JJ, Dees MK, van Zuylen L, Szadek KM et al. Use of antithrombotics at the end of life: an in-depth chart review study. BMC Palliat Care. 2021; 20(1): 110.
- Hull RD, Garcia DA, Burnett AE. Heparin and LMW heparin: Dosing and adverse effects. Wellesley, Massachusetts. UpToDate; 2022.
- Janus N. Is anaemia another bleeding risk in cancer-associated thrombosis? Blood 2020; 136(1): 15.
- Noble S. Venous thromboembolism and palliative care. Clin Med (Lond). 2019; 19(4): 315-8.
- Tardy B, Picard S, Guirimand F, Chapelle C, Danel Delerue M, Celarier T, et al. Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study. J Thromb Haemost. 2017; 15(3):420-8.
- Zabrocka E, Wojtukiewicz MZ, Sierko E. Thromboprophylaxis in cancer patients in hospice. Adv Clin Exp Med. 2018; 27(2): 283-9.