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National Clinical Guideline Centre – Acute and Chronic Conditions (UK). Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. London: Royal College of Physicians (UK); 2010. (NICE Clinical Guidelines, No. 92.)

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Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital.

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26Cancer

26.1. Introduction

Active cancer is an additional risk factor for VTE and the prothrombotic tendency varies with tumour type556. Furthermore, many surgical procedures are carried out as part of curative or palliative cancer treatment.

Whilst the increased bleeding risk of cancer patients receiving full anticoagulation is well recognised when compared to non cancer patients, there has been no evidence identified suggesting this is the case with primary thromboprophylaxis. However the studies reviewed excluded those at highest risk of bleeding. Based on the clinical evidence standard contraindications to VTE prophylaxis should apply to this group.

This chapter deals with two populations:

  • cancer patients admitted to hospital with an acute illness which may or may not be due to their cancer diagnosis
  • cancer patients admitted to hospital for oncological treatment.

For patients with cancer who are undergoing surgery, refer to guidance provided for the specific types of surgery in chapters 9 to 18.

26.2. Evidence of methods of prophylaxis

26.2.1. Summary of comparisons identified for any outcome

A number of studies reported on the use of VTE prophylaxis in general medical patients, and most of these trials 45,121,141,191,350,387,390,395,418,579 included some cancer patients within their population, although the proportion of patients included varied. The full review of these studies is detailed in chapter 23 and details on the proportion of cancer patients included can be found in the evidence tables (Appendix D).

All included RCTs were either individually critically appraised to be of a high quality (level 1+ or level 1++) or came from systematic reviews of RCTs which had been critically appraised to be of a high quality (level 1+ or level 1++).

Although a number of studies have been completed which investigate the potential anti-cancer properties of anticoagulants, only studies reporting VTE outcomes were included in this review. Only one study was identified which met these criteria which compared adjusted low dose warfarin (target INR 1.3–1.9) against no prophylaxis in women with metastatic breast carcinoma 398. The average duration of prophylaxis in this study was 180 days.

Figure 26-56. Number of studies which compared various types of prophylaxis methods.

Figure 26-56Number of studies which compared various types of prophylaxis methods

Numbers in boxes indicate the number of RCTs for each comparison. Boxes shaded grey indicates areas where no studies were identified.

GCS – anti-embolism/graduated compression stockings; IPCD/FID – intermittent pneumatic compression devices or foot impulse devices; LMWH – low molecular weight heparin; UFH – unfractionated heparin; Asp (HD) – high dose aspirin (>300mg), Asp (LD) - low dose aspirin (< 300mg); mech – mechanical prophylaxis (i.e. anti-embolism/graduated compression stockings, intermittent pneumatic compression devices or foot impulse devices); pharm – pharmacological prophylaxis

26.2.3. Additional information

26.2.3.2. Other outcomes

No studies reported chronic thromboembolic pulmonary hypertension or post-thrombotic syndrome.

26.3. Network meta-analysis results

Network meta-analysis was not completed for this population.

26.4. Cost-effectiveness evidence

No cost-effectiveness model was created for this population.

26.5. Patient views

One study qualitative study was conducted among 28 cancer patients receiving palliative care in the UK492. This study recruited patients who received LMWH for at least 5 days, and recruitment stopped when theme saturation was achieved. The study found that patients were aware of the purpose of subcutaneous LMWH thromboprophylaxis, and they understood that death could be a consequence of VTE. The potential benefit of reducing the risk of VTE was balanced against potential side effects (bruising was quoted) and patients found it acceptable to receive the LMWH injections492 (Evidence table 62, Appendix D).

Patient views about specific prophylaxis agents are within section 6.6.

26.6. Summary of evidence

Table 26-137Summary of evidence from network meta-analysis results for DVT, symptomatic pulmonary embolism and major bleeding outcomes

Intervention(s)Comparison(s)Intervention favoured
DVTSymp PEMB
Prophylaxis vs no prophylaxis
VKAnil-Not sigNot sig
Cost-effectiveness
No cost-effectiveness model was completed for this population

The prophylaxis strategy which is significantly more effective in reducing DVT or symptomatic PE; or resulting in significantly less major bleeding is stated in bold. Not sig = not a statistically significant difference ‘-’ = not reported. MB = Major bleeding

26.7. Recommendations and link to evidence

RecommendationOffer pharmacological VTE prophylaxis to patients with cancer who are assessed to be at increased risk of VTE (see Section 5.9). Choose any one of:
  • LMWH*
  • UFH (for patients with renal failure).
Start pharmacological prophylaxis as soon as possible after risk assessment has been completed. Continue until the patient is no longer at increased risk of VTE.
*At the time of publication (January 2010) some types of LMWH do not have UK marketing authorisation for VTE prophylaxis in medical patients. Prescribers should consult the summary of product characteristics for the individual LMWH. Informed consent for off-label use should be obtained and documented.
Recommendation –from section 5.9Regard medical patients as being at increased risk of VTE if they:
  • have had or are expected to have significantly reduced mobility for 3 days or more, or
  • are expected to have ongoing reduced mobility relative to their normal state and have one or more of the risk factors in Box 1.
Box 1 –Risk Factors for VTE
  • Active cancer or cancer treatment
  • Age over 60 years
  • Critical care admission
  • Dehydration
  • Known thrombophilias
  • Obesity (BMI over 30 kg/m2)
  • One or more significant medical comorbidities (for example: heart disease; metabolic, endocrine or respiratory pathologies; acute infectious diseases; inflammatory conditions)
  • Personal history or first-degree relative with a history of VTE
  • Use of hormone replacement therapy
  • Use of oestrogen-containing contraceptive therapy
  • Varicose veins with phlebitis
  • For women who are pregnant or have given birth within the previous 6 weeks see Chapter 30 (Pregnancy and up to 6 weeks post partum)
Relative values of different outcomesThe outcomes identified as important by the Guideline Development Group were thromboembolic events (asymptomatic and symptomatic DVT, symptomatic pulmonary embolism and fatal pulmonary embolism), bleeding events (major bleeding, fatal bleeding and stroke) and other long term events occurring as a result of VTE (chronic thromboembolic pulmonary hypertension and post thrombotic syndrome).
The Guideline Development Group noted that although the reduction of risk of fatal events was the most important outcome, when the evidence was reviewed for general medical patients there was not enough evidence to conclude that prophylaxis reduced all cause mortality.
In the absence of this evidence the Guideline Development Group identified symptomatic VTE and bleeding events as the most important outcomes.
Trade off between clinical benefit and harmsThe benefit of reducing VTE events is balanced with the potential harms of bleeding due to anticoagulation.
Economic considerationsAn economic model was developed for general medical patients. The model concluded that LMWH and UFH were the most cost-effective strategies in general medical patients.
However, the cost-effectiveness of drug prophylaxis in cancer patients is harder to assess because although these patients have increased risk of VTE they might also have an increased risk of bleeding. Furthermore, the QALYs gained might be less for cancer patients if their life expectancy is low even in the absence of a VTE.
Quality of evidenceAll included RCTs were either individually critically appraised to be of a high quality (level 1+ or level 1++) or came from systematic reviews of RCTs which had been critically appraised to be of a high quality (level 1+ or level 1++).
The quality of the evidence specific to cancer patients was low. Although 92% (12/13) RCTs of prophylaxis in general medical patients included some patients with cancer, there was only one study which provided results specifically for this population 579. This showed that LMWH reduced VTE events by approximately 50% compared with no prophylaxis, although this was not statistically significant, probably due to the small numbers of patients included (72 cancer patients).
The quality of the studies for general medical patients has been discussed elsewhere (chapter 23).
Other considerationsNone
RecommendationDo not routinely offer pharmacological or mechanical VTE prophylaxis to patients with cancer having oncological treatment who are ambulant.
Relative values of different outcomesThe outcomes identified as important by the Guideline Development Group were thromboembolic events (asymptomatic and symptomatic DVT, symptomatic pulmonary embolism and fatal pulmonary embolism), bleeding events (major bleeding, fatal bleeding and stroke) and other long term events occurring as a result of VTE (chronic thromboembolic pulmonary hypertension and post thrombotic syndrome).
The Guideline Development Group agreed that reducing the risk of symptomatic VTE balanced against the risk of major bleeding were the most important outcomes.
Trade off between clinical benefit and harmsThe benefit of reducing VTE events is balanced with the potential harms of bleeding due to anticoagulation.
Economic considerationsThere was no economic model developed for this population.
The GDG considered that, as with other patient groups, if these patients are ambulant the risk of VTE is not large enough to justify the adverse events and costs of prophylaxis.
Quality of evidenceAll included RCTs were either individually critically appraised to be of a high quality (level 1+ or level 1++) or came from systematic reviews of RCTs which had been critically appraised to be of a high quality (level 1+ or level 1++).
There was only one study investigating prophylaxis for the reducing the risk of VTE in patients undergoing treatment for cancer 398. This was a small study (n=315) of people undergoing treatment for breast cancer and so these data may not be applicable to other populations. Likewise, this was an ambulant population with prophylaxis provided over 180 days. Additionally, this study was published more than 10 years ago and since then treatment methods have changed.
Other considerationsIf these patients have central venous catheters, more guidance for this population can be found in Chapter 27.

26.7.1. Other recommendations of relevance

The specific recommendations for patients with cancer in this chapter should be read in conjunction with other relevant recommendations presented elsewhere in the guideline. These are:

26.8. Recommendations for research

The current evidence for thromboprophylaxis in hospitalised cancer patients is based on studies in general medical patients that had included cancer patients. Therefore a study to identify best practice within the cancer population alone should be conducted.

Recognition that some cancers are more thrombogenic than others, supports a view that this should be done in specific cancer groups. Such cancer groups worthy of consideration include myeloma, pancreatic, lung, ovarian and primary brain.

New oral anticoagulant agents such as dabigatran and rivaroxaban should be evaluated in the general cancer population.

26.9. Summary of recommendations

  • Offer pharmacological VTE prophylaxis to patients with cancer who are assessed to be at increased risk of VTE (see Section 5.9). Choose one of the following:
    Start pharmacological prophylaxis as soon as possible after risk assessment has been completed. Continue until the patient is no longer at increased risk of VTE.
  • Regard medical patients as being at increased risk of VTE if they:
    • have had or are expected to have significantly reduced mobility for 3 days or more, or
    • are expected to have ongoing reduced mobility relative to their normal state and have one or more of the risk factors shown in Box 1.
  • Do not routinely offer pharmacological or mechanical VTE prophylaxis to patients with cancer having oncological treatment who are ambulant.
Box Icon

Box 1

Risk factors for VTE. Active cancer or cancer treatment Age over 60 years

Footnotes

1

At the time of publication (January 2010) some types of LMWH do not have UK marketing authorisation for VTE prophylaxis in medical patients. Prescribers should consult the summary of product characteristics for the individual LMWH. Informed consent for off-label use should be obtained and documented.

Copyright © 2010, National Clinical Guideline Centre - Acute and Chronic Conditions.

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Bookshelf ID: NBK116533

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