British Geriatrics Society

Prophylaxis for Venous Thromboembolism

1. Executive and Lay Summary

Venous thromboembolism (blood clots) is a common occurrence in medical admissions, and can be significantly reduced through prophylaxis (preventive treatments). Unfortunately both the risks of thrombosis and of prophylaxis are increased in frail older people, and this means that careful risk assessment to weigh up risks and benefits in each patient is essential. Indeed the Department of Health has mandated risk assessment for thrombosis for all admissions. This guideline highlights the situations where the risk of treatment may outweigh the risk of thrombosis, and where prophylaxis may be viewed as an unwelcome burden. Perhaps surprisingly recent reviews by Cochrane and NICE have found that overall mortality in medical admissions is probably unaffected by thromboprophylaxis. Our hope is that this guideline will help geriatricians make better judgements of how to use thromboprophylaxis wisely and safely.

2. Introduction

Deep vein thrombosis is common during hospital admission, and pulmonary embolism can be fatal. In order to reduce preventable deaths, the Department of Health has mandated the assessment of Venous ThromboEmbolism (VTE) risk in all admissions [1], and NICE has published a thorough review of the evidence [2]. The key risk factors are age over 60, recent immobility due to illness, prior VTE, active cancer, COPD, heart failure, obesity and sepsis. Geriatric Medicine clearly manages patients with multiple risk factors, but also covers a wide casemix ranging from previously healthy individuals with a severe acute illness to those with multiple comorbidities admitted with worsening disability requiring medical treatment, rehabilitation or symptomatic care. Geriatricians are familiar with tailoring treatments to the individual. It is important that current VTE guidelines are applied appropriately: the risk of giving treatment might fail to respect the wishes or best interests of the patient, and risks might outweigh potential benefits. This guideline is written to assist practitioners apply national policy to individual patients.

3. Definitions / Terminology

It is estimated that 25,000 hospital deaths are due to pulmonary embolism, and 75% of these deaths are in medical patients. However, according to ONS statistics, pulmonary embolism is the underlying cause of death much less commonly – around 0.6% of all deaths – and this is unrelated to age [3]. The risk of VTE in medical admissions varies from 15% in general medical patients to 50% in stroke patients, while clinically significant PE occurs in 1% [4].. Fatal PE is an infrequent consequence of the far more frequent event of deep vein thrombosis (DVT). DVT often goes unnoticed, and can result in long-term leg complications of post-thrombotic syndrome.  This guideline is restricted to reviewing VTE prophylaxis in medical admissions. However, the precautionary principles could be applied to other settings, although the evidence-base for the benefits of each mode of prophylaxis is different for each setting, and this is fully explored in the NICE guideline.

4. The evidence-base for VTE prophylaxis in medical admissions

Prophylaxis has been reviewed by Cochrane [4] and NICE [2]. There are 5 RCT’s comparing Low Molecular Weight Heparin (LMWH) to placebo in the prevention of PE, and 4 comparing LMWH to Unfractionated heparin (UFH). Trials generally administered treatment for up to 10 days. LMWH treatment reduced the incidence of  DVT by 60%, and symptomatic PE by 39% compared to placebo (RR 0.61, 95%CI 0.25,1.5) [2]. Major haemorrhage was increased by LMWH vs placebo (RR 1.76, 95%CI 0.79, 3.26) but is less than with UFH. For every 400 patients treated with LMWH, one symptomatic PE is prevented at the cost of two serious haemorrhages. Minor haemorrhage is increased from around 2% to 3.7% [2]. All cause mortality is not significantly affected by thromboprophylaxis (RR 0.94, 0.80, 1.09), being swamped by much larger alternative causes, and so the evidence for preventable deaths in the context of medical admissions is weak.

Older people are more sensitive to the effects of warfarin, but sensitivity to heparin is less clear: heparin is metabolised by the liver, but also excreted unchanged by the kidney. The major trials excluded patients with creatinine >150, and so the safety profile in older people with renal failure is unknown. [Accumulation is acknowledged by Dalteparin SPC, although no dose reduction recommended; Enoxaparin’s SPC advises halving the dose where GFR is <30mls/min]

The optimal duration of thromboprophylaxis has had very limited attention from RCT’s -  DVT can develop up to 6 weeks after an acute illness. Published trials have been in a casemix with rapid recovery of mobility. Prolonged prophylaxis for 4 weeks after the recovery of immobility was beneficial in one study (“EXCLAIM” [5]) which has never been fully reported because of concerns regarding methodology. Probably because of the lack of published evidence, LMWH’s are recommended  for up to 14 days according to their Summary of Product Characteristic (SPC).

NICE recommended that only those who have recent immobilisation are considered at risk – patients who are wheelchair bound or bed-bound are not thought to be at high risk of PE when admitted. It is believed that the risk of DVT and PE diminishes over time following immobilisation. This has been studied mainly in spinal injuries, but also in Parkinson’s Disease and Multiple sclerosis [6]. The mechanism for reduced risk is thought to be due to contraction of the venous pooling over time. This occurs after 3 months of immobility.

For patients with contra-indications to LMWH, consideration may be given to anti-embolism stockings. NICE concluded that it was unknown whether the benefits outweighed the harm in medical patients as there have been no studies, although there is clear evidence from CLOTS trial that stockings are ineffective in stroke patients [7], and cause harm through cutaneous adverse events. The risk of harm will be higher in patients with peripheral vascular disease, which will be common in an older population.

5. Precautions in managing older people

The foreword to the NICE guideline describes the balance of risk and benefit in this whole area:
“It is a clinical problem which requires a meticulously researched and analysed evidence base. The potential health gains for the optimal strategy are great. An individual team will have patients who suffer PE and patients whose recovery is complicated by a treatment related bleed. The clinical difficulty is that both fatal pulmonary embolism and major bleeding have low event rates affecting fewer than one in a hundred patients.”

Unfortunately that evidence-base does not exist for most patients seen by geriatricians.

Contra-indications for thromboprophylaxis are in the DH checklist, and include bleeding disorders and low platelet count, and apply regardless of age of patient.

The following issues in geriatric medicine require special consideration:

A.    Many older patients are confused in hospital, either from delirium or dementia, and will be unable to give consent to treatment. This will usually mean that the consultant must assume responsibility of making a best interests judgement on the value of treatment on behalf of the patient.

B.    The skin in older people is frequently more fragile, and easily bruised. Older people are probably more likely to suffer from local bruising and minor haemorrhages at the injection site. This may cause pain and discomfort, in a patient who is perhaps unable to understand the reason for the treatment, and this may undermine rehabilitation.

C.    Some patients are near end-of-life where their admission and treatment have goals of relieving symptoms and not necessarily prolonging life. For these people, injections are an additional unwelcome burden.

D.    There may be accumulation of LMWH’s in moderate to severe renal failure despite dose adjustment recommended in the SPC’s, which will increase the risk of haemorrhage over time. Prophylaxis dose should probably be halved where eGFR is <30mls/min.

E.    Patients who are usually immobile have less chance of benefiting from prophylaxis. It may be difficult to ascertain prior mobility status.

F.    Patients who are at risk of multiple falls will have an enhanced risk of serious bruising from prophylaxis.

G.    Mortality risk from PE and from major haemorrhage are both increased in older people.

H.    Prolonged prophylaxis in medical patients increases the haemorrhage risk without (at present) evidence for further benefit, and is currently off-licence. 

I.    Anti-embolism stockings should only be used with caution and skin integrity must be carefully and regularly monitored.

J.    Extra caution should be taken with patients admitted to Community Hospitals, where for example blood tests may be less frequent or not undertaken on the day of admission. It is important ensure that contra-indications to prophylaxis are carefully identified and reviewed.

6. Responsibilities / Role of the Geriatrician

The geriatrician has a duty to ensure non-ageist practices, and all patients must have a risk assessment undertaken on admission to hospital. National guidance has mandated the risk assessment [1], but not mandated the action that is to be undertaken. The geriatrician must weigh up for each individual the relative risks and potential benefits of thromboprophylaxis, as for every other drug on the prescription chart. This should include consideration of the following:

A.    Level of risk – seriousness of the acute medical condition, combination of risk factors.

B.    Capacity to benefit – previously immobile patient; end-of-life or very frail patients for symptomatic care.
Where a decision is made to continue prophylaxis beyond one week, it will be important to monitor the patient carefully for

• The development of bruises, especially if causing distress
• Platelet count and haemoglobin.

Documentation of the decision making process is essential.

7. Audit

Hospitals are required to audit regularly their adherence to thromboprophylaxis regimes. Geriatricians should ensure that such audits are able to identify not only whether a risk assessment was carried out, but also whether treatment was judged inappropriate. Attention should be given to recording factors such as prior immobility and symptom-only care.

8. Training

Departments  of geriatric medicine should train their juniors who are working in the acute take on the principles of weighing up risks and benefits for thromboprophylaxis

9. Recommendations

Geriatricians should ensure high quality risk assessment of VTE for all patients under their care. They should be informed of the risks and benefits of thromboprophylaxis, and take responsibility for its appropriate use. Local policies should ensure that prophylaxis is not administered where the risks and burden may outweigh potential benefit. 

10. References

1. Department of Health. Venous thromboembolism Risk Assessment. March 2010. Gateway reference 10278
2. Venous thromboembolism: reducing the risk of venous thromboembolism in patients admitted to hospital. National Clinical Guideline Centre Jan 2010. http://guidance.nice.org.uk/CG92
3. Office for National Statistics. Mortality Statistics 2008. http://www.statistics.gov.uk/downloads/theme_health/DR2008/DR_08.pdf
4. Alikhan R, Cohen AT Heparin for the prevention of venous thromboembolism in general medical patients Cochrane Database of Systematic Reviews 2009 Issue 3.
5. Hull RD, Schellong SM, Tapson VF et al Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility. XXI Congress of the International Society on Thrombosis and Haemostasis Geneva 2007.
6. Gaber T A-Z K  Significant reduction of the risk of venous thromboembolism in all longterm immobile patients a few months after the onset of immobility. Medical Hypotheses 2005;64:1173-6.
7. CLOTS Trials collaboration. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke: a multicentre, randomised controlled trial. Lancet 2009;373:1958-66.