During the 10th ICTHIC, Professor Simon Noble (Cardiff University, UK) talked about the management of VTE in patients in palliative care. Here we report the key messages of his presentation.
The cancer journey changes over time, and the risk of VTE follows it, being higher during hospitalization, decreasing during remission, and rising again during metastasis development and end of life .
Although many guidelines exist on the management of cancer-associated thrombosis (CAT), no specific guidelines exist on the palliative care population. One systematic review and metanalysis looked at the management of VTE in patients with advanced cancer, but the conclusions are based on data from a healthier population .
Also, it is not easy to define a palliative care population, as palliative care has many meanings for the oncologist, general practitioner, and patient.
The World Health Organization (WHO) defines palliative care as an approach that “improves patients’ quality of life and of their families who are facing challenges associated with life-threatening illness, whether physical, psychological, social or spiritual.”
Although this definition highlights the holistic management that should be applied to a patient with an incurable disease, it does not give a precise definition of the palliative care population, which can be used as inclusion criteria for clinical studies .
CAT management in palliative care
The management of CAT in palliative care has to be guided by the evaluation of the available data on patients with CAT, even though the two populations are different The palliative care patients are not represented in these studies, and the collected data tends to be largely observational.
In CAT studies, primary outcomes tend to be VTE recurrence, bleeding, and, perhaps, overall survival. Most of the patients will have normal or near to normal hepatic and renal function, and they will be receiving systemic anti-cancer therapies, surgery, and radiotherapy .
There is a paradigm shift in palliative cancer patients from a cure to prolong life to a cure that assures the best quality of life possible through symptom control. Unfortunately, palliative patients generally have deranged biochemistry and are less likely to receive systemic anti-cancer therapies while likely receiving supportive medicine. Also, they would have an Eastern Cooperative Oncology Group (ECOG) performance status higher than 2, a prognosis of fewer than three months, and weight less than 40 kilos .
For these reasons, trials on patients with CAT do not adequately represent patients in palliative care.
CAT treatment of palliative care patients
Palliative cancer patients have an increased risk of thrombosis and markedly increased risk of bleeding. They are often nearing the end of life with many comorbidities. Hepatic and renal function will be variable and deteriorating. They have poorer oral absorption of drugs and multiple pharmacology, which carry a potential for drug-drug interactions .
Since specific data on drugs in palliative cancer patients do not exist, and treatment management is based on data extrapolations from advanced cancer studies.
What is known is that even with regular monitoring and control of the International Normalized Ratio (INR), advanced cancer patients have a higher rate of bleeding with warfarin . Also, palliative cancer patients might experience multiple drug-drug interactions with the subsequent requirement for frequent drug monitoring .
Clinical guidelines recommend using low molecular weight heparin (LMWH) for the management of patients with CAT. With LMWH, it is possible to monitor absorption levels and adjust the dose if necessary .
Although a daily injection might be challenging in a long-term perspective, qualitative studies in palliative care patients suggest that the daily injection is acceptable in the context of their disease and their experiences .
Recently, direct-oral anticoagulants (DOACs) have become an alternative CAT treatment in specific circumstances. However, no studies are available in the published literature about their use in palliative care treatment . Also, not much data is available in the use of DOACs in the lower extremes of the body weight curve, cerebral disease, or severe thrombocytopenia.
DOACs cannot be used in patients at high risk of bleeding (as advanced cancer patients and palliative care patients are), and caution is recommended for their use in gastrointestinal cancers. Also, since palliative cancer patients have poorer oral drug absorption, DOACs might not be the best drugs .
Anticoagulants and hospice
A study on 22 palliative care units (1199 patients) looked at clinically relevant bleeding rates, and it showed a rate of 9.8% (95% CI 8.3-11.6). Most of the population had cancer (91%) with metastatic disease (77.5%), and 48% of patients were receiving LMWH thromboprophylaxis and 5.7% therapeutic LMWH. The multivariate analysis suggested an association between bleeding complications and pharmacological thromboprophylaxis (HR 1.48, 95% CI, 1.02–2.15; P=0.04). However, the low number did not allow comparison of bleeding and full-dose anticoagulation .
In a case series of 457 patients with CAT and a broad spectrum of cancer diseases, 192 patients died over a year and a half following up. Of these, 50% continued anticoagulation until death and 11% until seven days before death. In addition, 7% of the patients who continued anticoagulation within seven days from death experienced clinically relevant non-major bleeding .
Thromboprophylaxis in the hospice
Thromboprophylaxis in the hospice is has been debated for some time. One of the reasons is that palliative care teams question its utility and whether the outcome measures used are relevant to a palliative care population.
A study recruited patients from five specialist palliative care units (excluding those with an estimated prognosis lower than five days) to test the prevalence of femoral deep vein thrombosis (DVT) within 48 h of admission. Patients underwent bilateral femoral vein ultrasonography on admission and weekly until death or discharge for a maximum of 3 weeks .
About a third of patients admitted with advanced cancer had a femoral DVT. However, no survival difference was registered between those who had thrombosis or received thromboprophylaxis and those who did not. Also, recurrent VTE symptoms were rarely reported .
As previously said, in advanced cancer patients, the risk of significant bleeding increases as death approaches. Also, primary and secondary prophylaxis and antiplatelet agents do increase bleeding risk too.
For all these reasons, it seems reasonable to stop anticoagulation as death approaches .
Prof Noble’s clinical practice.
“I treat the anticoagulant like any other drug with a patient approaching end of life, and I rationalize it,” said Prof Noble. “The question is always what is this medicine doing? If it supports a symptom, prevents it, or treats it, one can consider keeping the anticoagulation on. But I think that, at the end of life, symptoms attributable to VTE can be managed with other medicines, especially in patients who’ve been anticoagulated for some time.”
Palliative care patients are a peculiar category, and the main challenge lies in identifying who they are. Unfortunately, a definition of a palliative patient is very hard to obtain, pointing out the need for an individualized approach.
Palliative care should be symptom- and patient-focused rather than clot-focused. There should be a lower threshold for stopping anticoagulants as death approaches and a careful selection of patients who should receive thromboprophylaxis.
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7. Tardy B, Picard S, Guirimand F, et al. Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study. J Thromb Haemost. 2017;15(3):420-428. doi:10.1111/jth.13606
8. Noble S, Banerjee S, Pease NJ. Management of venous thromboembolism in far-advanced cancer: current practice [published online ahead of print, 2019 Jun 25]. BMJ Support Palliat Care. 2019;bmjspcare-2019-001804. doi:10.1136/bmjspcare-2019-001804
9. White C, Noble SIR, Watson M, 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 [published correction appears in Lancet Haematol. 2019 Jun;6(6):e294]. Lancet Haematol. 2019;6(2):e79-e88. doi:10.1016/S2352-3026(18)30215-1