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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.)

31Patients requiring antiplatelet agents and anticoagulants for other reasons

31.1. Antiplatelet agents

Aspirin, clopidogrel and dipyridamole are prescribed for their anti-platelet actions. Aspirin has been shown to be beneficial to patients with arterial blood vessel disease at a dose of 75mg daily. At this dose it has minimal anti-thrombotic effect. Even at high doses (greater than 300mg daily) it is less efficient at reducing the risk of VTE formation than standard pharmacological methods. Clopidogrel although prescribed predominantly for its antiplatelet effect in the treatment of acute coronary syndromes and following stent insertion is not licensed for VTE prophylaxis as a single agent and is less cost effective than standard pharmacological methods (chapters 9-1). Dipyridamole is used as an adjunct to anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. It is also licensed for secondary prevention of ischaemic stroke and transient ischaemic attacks. There are no trials regarding its efficacy in the prophylaxis of VTE.

Patients admitted to hospital whilst taking these medicines are required to have assessment of their VTE risk performed (chapter 5). Patients who have a clinical need for their anti-platelet agents should continue to take their medication. Patients who are assessed as being at increased risk of VTE should receive appropriate prophylaxis with low molecular weight heparin (LMWH) or fondaparinux, once the bleeding risk is reviewed and has been established as low. Mechanical methods can be used where appropriate or if the bleeding risk is considered to be too high for additional pharmacological prophylaxis.

31.2. Recommendations and link to evidence

RecommendationDo not regard aspirin or other antiplatelet agents as adequate prophylaxis for VTE.
RecommendationConsider offering additional mechanical or pharmacological VTE prophylaxis to patients who are having antiplatelet agents to treat other conditions and who are assessed to be at increased risk of VTE (see section 5.9). Take into account the risk of bleeding (see Box 2) and of comorbidities such as arterial thrombosis.
Recommendationfrom 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 – 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 (such as heart disease, metabolic, endocrine or respiratory pathologies, acute infectious diseases or inflammatory conditions)
  • Personal history or a 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)
Recommendation–from section 5.9Assess all patients for risk of bleeding before offering pharmacological VTE prophylaxis *. Do not offer pharmacological VTE prophylaxis to patients with any of the risk factors for bleeding shown in Box 2, unless the risk of VTE outweighs the risk of bleeding.
*Consult the summary of product characteristics for the pharmacological VTE prophylaxis being used or planned for further details.
Box 2-Bleeding Risk Factors
  • Active bleeding
  • Acquired bleeding disorders (such as acute liver failure)
  • Concurrent use of anticoagulants known to increase the risk of bleeding (such as warfarin with INR higher than 2)
  • Lumbar puncture/epidural/spinal anaesthesia expected within the next 12 hours
  • Lumbar puncture/epidural/spinal anaesthesia within the previous 4 hours
  • Acute stroke
  • Thrombocytopenia (platelets less than 75 × 109/l)
  • Uncontrolled systolic hypertension (230/120 mmHg or higher)
  • Untreated inherited bleeding disorders (such as haemophilia and von Willebrand’s disease)
Relative values of different outcomesThe outcomes considered important by the Guideline Development Group (GDG) 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).
Additionally patients who are receiving antiplatelet agents are likely to have additional comorbidities, such as a high arterial side thrombosis risk. These factors meant that the GDG felt that although existing antiplatelet agents should not be stopped, additional thromboprophylaxis should be considered to ensure that patients are adequately protected.
Trade off between clinical benefit and harmsThe risks of developing VTE may be high and these need to be weighed up against the risks of possible side effects such as bleeding which is increased if antiplatelet agents are also being used.
Economic considerationsThere is no relevant cost-effectiveness evidence specifically for this population subgroup.
In four out of five of the population subgroups that we modelled, there was enough evidence to include aspirin (Chapters 9 to 12). In all four models, aspirin alone was one of the least effective strategies at increasing quality adjusted life years (QALYs) and least cost-effective. Conversely low molecular weight heparin (LMWH) was consistently one of the most effective and cost-effective strategies. Mechanical prophylaxis in population subgroups where there is evidence, also seems to be more effective and cost-effective than aspirin alone.
Two of our models (Chapters 9 and 10) considered the combination of high dose aspirin and unfractionated heparin. In both cases the strategy reduced QALYs compared with no prophylaxis and hence the combination was neither effective nor cost-effective. This was due to a very high bleeding increase, as estimated from our network meta-analysis. However, these studies did use very high doses of aspirin (sometimes up to 1000mg per day).
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 evidence for adding other pharmacological agents to aspirin is very sparse. There are two studies in general surgery patients where all patients received high dose aspirin (>300mg per day) and patient in one arm of the trial also received UFH. These trials reported a significant decrease in DVT events and a significant increase in major bleeding (Forest plots 149151, Appendix E).
There were five studies in patients undergoing surgery (2 general surgery, 1 elective hip replacement surgery, 2 mixed surgery) which compared the addition of high dose aspirin (>300mg per day) to a background of UFH, which was received by patients in both arms of the study. The combined results of these studies do not report any statistically different findings for DVT, PE or major bleeding (Forest plots 161163, Appendix E).
In addition, two studies in stroke patients which add UFH or LMWH to aspirin (unknown dose). Combining these studies showed that LMWH and aspirin had a statistically significant reduction in DVT events without significant increase in bleeding compared with UFH and aspirin (chapter 24, Forest plots 183186, Appendix E).
Other considerationsThe GDG found it difficult to identify situations where it was clear that pharmacological thromboprophylaxis should be used in addition to antiplatelet agents and felt that healthcare professionals should use guidance provided in the BNF or summary of product characteristics for the agents being used or those which are planned. Individual assessment of the risks and benefits is key and this is likely to require clinical judgement.
For patients in whom additional pharmacological thromboprophylaxis was deemed inappropriate but who are considered at high risk of VTE, mechanical methods (such as anti-embolism stockings, intermittent pneumatic compression devices) can be considered as an alternative which does not increase the risk of bleeding. Where mechanical methods are provided they should be used in line with the recommendations in section 6.7.

31.3. Anticoagulant agents

Patients who are admitted who are already receiving anticoagulation therapy, or who are started on full dose anti-coagulation using heparin, do not require additional pharmacological VTE prophylaxis. Patients (including those admitted taking oral thrombin or oral Xa inhibitors) should still have a VTE assessment performed (section 5.9). Treatment should be continued unless a clinical contraindication has arisen. If treatment is stopped the patients are at risk of VTE and they should be considered for VTE prophylaxis accordingly.

31.3.1. Warfarin bridging

Some patients admitted to hospital for surgical procedures will already be receiving warfarin. Healthcare professionals involved in their care will be required to make decisions about whether to, and when to stop, the warfarin and replace with other anticoagulant agents such as low molecular weight heparin. Warfarin bridging was not prioritised for a full systematic review. However, the guideline development group considered it to be an important and complex area which will involve the assessment of risks and benefits for each patient. An example of a strategy for warfarin bridging is included in Appendix H. When unsure of the appropriate action to take, healthcare professionals should consult colleagues with specialist knowledge in this area.

31.4. Recommendations and link to evidence

RecommendationDo not offer additional pharmacological or mechanical prophylaxis for VTE to patients who are taking vitamin K antagonists and who are within their therapeutic range, providing anticoagulant therapy is continued.
Relative values of different outcomesThe outcomes considered important by the GDG 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).
Trade off between clinical benefit and harmsThe risk of developing venous thromboembolism is weighed against the increase risk in bleeding caused by pharmacological prophylaxis.
Economic considerationsThere is no relevant cost-effectiveness evidence specifically for this population subgroup.
Vitamin K antagonists (VKA) are shown to be an effective and cost-effective strategy in several groups of patient (Chapters 9 to 12). In the case of patients already on VKAs, they can obtain the benefits of prophylaxis without any additional drug and monitoring costs.
Quality of evidenceThere is evidence across a number of different populations that vitamin K antagonists are effective at reducing the risk of VTE.
Other considerationsDoses of anticoagulants used for treatment are usually higher than for prophylaxis use and so are likely to be suitable for reducing VTE risk although they will increase bleeding risk. .
RecommendationDo not offer additional pharmacological or mechanical prophylaxis for VTE to patients who are having full anticoagulant therapy (for example, fondaparinux sodium, LMWH or UFH).
Relative values of different outcomesThe outcomes considered important by the GDG 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).
Trade off between clinical benefit and harmsThe risk of developing venous thromboembolism is weighed against the increase risk in bleeding caused by pharmacological prophylaxis.
Economic considerationsThere is no relevant cost-effectiveness evidence specifically for this population subgroup.
These drugs have been shown to be an effective and cost- effective strategy in several groups of patient (Chapters 9 to 12 and 23). In the case of patients already on these drugs, they can obtain the benefits of prophylaxis without any additional drug and costs.
Quality of evidenceThere is evidence across a number of different populations that LMWH, UFH and fondaparinux are all effective at reducing the risk of VTE.
Other considerationsDoses of anticoagulants used for treatment are usually higher than for prophylaxis use and so are likely to be suitable for reducing VTE risk although they will increase bleeding risk. .

31.4.1. Other recommendations of relevance

The specific recommendations for patients already using antiplatelets and/or anticoagulants in this chapter should be read in conjunction with other relevant recommendations presented elsewhere in the guideline. These are:

31.5. Recommendations for research

A top priority research recommendation was identified for the use of prophylactic-dose anticoagulants in stroke patients (section 2.3.4).

31.6. Summary of recommendations

  • Do not regard aspirin or other antiplatelet agents as adequate prophylaxis for VTE.
  • Consider offering additional mechanical or pharmacological VTE prophylaxis to patients who are having antiplatelet agents to treat other conditions and who are assessed to be at increased risk of VTE (see section 5.9). Take into account the risk of bleeding (see Box 2) and of comorbidities such as arterial thrombosis.
  • 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 in Box 1

  • Regard surgical and trauma patients as being at increased risk of VTE if they meet one of the following criteria:
    -

    surgical procedure with a total anaesthetic and surgical time of more than 90 minutes, or 60 minutes if the surgery involves the pelvis or lower limb

    -

    acute surgical admission with inflammatory or intra-abdominal condition

    -

    expected significant reduction in mobility

    -

    have one or more risk factors shown in Box 1.

  • Assess all patients for risk of bleeding before offering pharmacological VTE prophylaxis. Do not offer pharmacological VTE prophylaxis to patients with any of the risk factors for bleeding shown in Box 2, unless the risk of VTE outweighs the risk of bleeding.
  • Do not offer additional pharmacological or mechanical prophylaxis for VTE to patients who are taking vitamin K antagonists and who are within their therapeutic range, providing anticoagulant therapy is continued.
  • Do not offer additional pharmacological or mechanical prophylaxis for VTE to patients who are having full anticoagulant therapy (for example, fondaparinux sodium, LMWH or UFH).
Box Icon

Box 2

Risk factors for bleeding. Active bleeding Acquired bleeding disorders (such as acute liver failure)

Box Icon

Box 1

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

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

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

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