Management of VTE and thromboprophylaxis in palliative care

It is acknowledged that cancer patients have a higher risk of developing pulmonary embolism (PE) and deep vein thrombosis (DVT) than the rest of the population due to the over-secretion and activation of thrombotic chemicals such as thrombin, tissue factor and factor VIIa1. The risk increases as the disease progresses. The Department of Health risk assessment for VTE in hospitals(2) should be applied to all patients being admitted and is a three-step process looking at i. mobility ii. patient-related factors increasing thrombosis risk and iii. patient-related factors increasing bleeding risk. It is for use in surgical and medical patients and active cancer or cancer treatment is included as a thrombosis risk, but other than that, the stage of disease or prognosis is not taken into account so it is not suitable for patients being admitted to a hospice.

Estimates of prevalence vary widely and there is a marked difference between that of clinically apparent VTE (around 15%) and asymptomatic VTE (50%)(3). The second figure mirrors that found on post-mortem. Although these figures are taken from older studies, they continue to be quoted in more recent papers so are still regarded as appropriate(4).

Not all DVTs result in PE and it seems that many patients are unaware of having the problem. Therefore it is difficult to find a consensus on whether all cancer patients should be offered prophylaxis as it involves an injection, which could be considered overly interventionalist.

There was also a time in the not so distant past when a fatal pulmonary embolism was regarded as not being a ‘bad death’. Opinions have switched over the last decade as clinicians acknowledged that death from a PE can be both painful and distressing. Some patients have reported that apart from the physical aspect, VTE can also be a source of significant psychological distress: some cancer patients described it as worse than their cancer experiences(5). This has led to palliative care clinicians considering thromboprophylaxis for those at highest risk but the area remains controversial. On the one hand we now have a section in the 2018 NICE guidance 2018(6) on VTE prophylaxis in palliative care, and on the other a 2019 comment article was published in The Lancet(7) where the authors query whether the high prevalence is a justification for treatment as many patients did not report symptoms.

Current NICE guidance NG89

 1.7.1 Consider pharmacological VTE prophylaxis for people who are having palliative care. Take into account temporary increases in thrombotic risk factors, risk of bleeding, likely life expectancy and the views of the person and their family members or carers (as appropriate).

• Use LMWH as first-line treatment
• If LMWH is contraindicated, use fondaparinux sodium

1.7.2 Do  not offer VTE prophylaxis to people in the last days of life.

1.7.3 For recommendations on shared decision-making in the last days of life, see the NICE guideline on care of dying adults in the last days of life (2018).

1.7.4 Review VTE prophylaxis daily for people who are having palliative care, taking into account the views of the person, their family members or carers (as appropriate) and the multidisciplinary team.

The latter article looked primarily at a longitudinal study by White et al(8) where 343 patients with advanced cancer in hospice units had ultrasound examinations on admission and each subsequent week and clinical signs and risk factors were recorded. Nearly a third had a detectable DVT on admission although most were symptomatic and the detection was not related to survival. It also quotes guidelines from the American Society of Clinical Oncology, which has declared that anticoagulation is of uncertain benefit in patients receiving end-of-life care. The argument for or against hinges on whether patients experience additional symptoms such as fatigue in the presence of a PE. As Zabrocka and Sierco(4) succinctly observe: in cancer VTE studies the primary outcome is often survival, whereas in palliative care, quality of life is the most relevant outcome.

Prescribing anticoagulants can often pose clinical uncertainty. Since low molecular weight heparins (LMWH) have become the treatment of choice for prophylaxis the complications of initiating and monitoring warfarin are removed, but the use of daily injections may seem inappropriate. The lack of licensed recommendations for longer-term medical use of some of the LMWHs can lead prescribers to question their suitability and there is a potential for increasing bleeding risk in susceptible patients. The introduction of the direct-acting oral anticoagulant drugs may eventually replace LMWHs but, as in so many cases, the evidence for their efficacy and tolerability in palliative care patients is not yet sufficiently robust.

The NICE guidance section 1.7 suggests ‘considering’ VTE prophylaxis for palliative care patients. It advises taking into account temporary increases in thrombotic risk factors, risk of bleeding, likely life expectancy and the views of the person and those close to them. It states VTE prophylaxis should not be offered in the last days of life. First-line treatment is currently LMWH and second is fondaparinux.

Professor Simon Noble has long had a deep interest in this topic and along with Professor Miriam Johnson has tried to clarify this clinical conundrum. Their 2010 editorial in Palliative Medicine(9) was entitled ‘Finding the evidence for thromboprophylaxis in palliative care: first let us agree on the question’. They discuss the need to define the palliative care patient, identify the true prevalence and natural history of VTE, develop appropriate outcome measures, identify the clinical and symptom burden, find a consensus on what outcome difference would be required to change thromboprophylaxis practice and, importantly, look at the cost effectiveness.

As part of this strategy, Professor Noble and a team of UK palliative care registrars from Newcastle instigated a one-day audit and evaluation of many UK hospices last month. They asked clinicians to record patient details, bleed history, medication, lab results and VTE risk assessment score.

Several of the hospices we support took part in this audit, with our pharmacists assisting in some, and they have submitted their results to the study group based in Newcastle. They stated their outcome measures and will publish the results in time.

Outcome measures for the UKPRC one-day audit

1. To record the number of patients with a documented VTE risk assessment.
2. To record the number of patients with NICE compliant thromboprophylaxis.
3. To detail the scope of non-compliance practice to identify patterns and areas to focus on as part of an improvement programme.
4. To explore the breadth of risk factors for VTE and contraindications to thromboprophylaxis in the palliative care inpatient population.

Some of the hospices took this opportunity to look at the current methods they had for risk assessments and realised they needed a more formalised and clearly documented decision-making process. We look forward to increasing our knowledge base on this complex and very specific therapeutic area.