Clinical Topic A-Z Clinical Speciality

Deep vein thrombosis

Deep vein thrombosis
D054556Venous Thromboembolism
D020246Venous Thrombosis
CardiovascularHaematology
2013-04-01Last revised in April 2013

Deep vein thrombosis - Summary

Deep vein thrombosis (DVT) is the formation of a thrombus (blood clot) in a deep vein, usually in the legs, which partially or completely obstructs blood flow.

DVT has an annual incidence of about 1 in 1000 people.

Continuing or intrinsic risk factors include:

Previous venous thromboembolism.

Cancer (known or undiagnosed).

Increasing age

Being overweight or obese

Male sex.

Heart failure.

Acquired or familial thrombophilia.

Chronic low-grade injury to the vascular wall (for example vasculitis, hypoxia from venous stasis, or chemotherapy).

Risk factors that temporarily raise the likelihood of DVT include:

Immobility.

Significant trauma or direct trauma to a vein (for example, intravenous catheter).

Hormone treatment (for example hormone replacement therapy).

Pregnancy and the postpartum period.

Dehydration.

The most serious complication is pulmonary embolism.

The possibility of DVT should be considered if typical symptoms and signs are present, especially if the person has risk factors. Typical signs and symptoms are:

Pain and swelling in one leg (occasionally both legs).

Tenderness, changes to skin colour and temperature, and vein distension.

Other conditions which may present with similar signs and symptoms include:

Physical trauma

Cardiovascular disorders such as superficial thrombophlebitis and post-thrombotic syndrome

Other conditions such as ruptured Baker’s cyst, cellulitis, and dependent oedema.

The two-level DVT Wells score should be used to assess the likelihood of DVT and inform further management.

For people who are likely to have DVT (based on the results of the two-level DVT Wells score), management includes:

Arranging referral for a proximal leg vein ultrasound scan to be carried out within 4 hours.

If a proximal leg vein ultrasound scan cannot be carried out within 4 hours of being requested, a blood sample should be taken for D-dimer testing; an interim 24-hour dose of a parenteral anticoagulant should be given; and a proximal leg vein ultrasound scan should be arranged (to be carried out within 24 hours of being requested).

For people who are unlikely to have DVT, a blood sample should be taken for D-dimer testing:

If the D-dimer test is positive, management options are as for people who are likely to have DVT.

If the D-dimer test is negative, an alternative diagnosis should be considered.

People with DVT require anticoagulant treatment in secondary care. On discharge they will require maintenance treatment with an oral anticoagulant drug for at least 3 months (provided there are no contraindications such as cancer or pregnancy) and compression stockings.

A person with DVT should be advised to:

Walk regularly after discharge from hospital.

Elevate the affected leg when sitting.

Refrain from extended travel, or travel by aeroplane, for at least 2 weeks after starting anticoagulant treatment.

Have I got the right topic?

192months3060monthsBoth

This CKS topic covers the identification and management of suspected deep vein thrombosis (DVT), and the subsequent prevention of venous thromboembolism (VTE).

This CKS topic does not cover the management of DVT and VTE in hospital, or the primary prevention of DVT. It does not cover the management of people with coagulation disorders or with recurrent DVT who require long-term anticoagulation.

There are separate CKS topics on Leg cramps, Leg ulcer - venous, and Thrombophlebitis - superficial. For information on prescribing issues associated with warfarin, see the CKS topic on Anticoagulation - oral. For information on the so-called 'economy class syndrome', see the CKS topic on DVT prevention for travellers. Information on the risk of VTE related to oestrogen therapy can be found in the CKS topics on Contraception - combined hormonal methods and Menopause.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in April 2013

December 2013 — minor update. Deleted duplicated text and removed reference to prescriptions in the CKS topic on Compression stockings.

April 2013 — reviewed. A literature search was conducted in March 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Based on the new NICE guideline: Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing, the recommendations for the management of suspected deep vein thrombosis has been revised to include the option of giving an interim 24-hour dose of parenteral anticoagulant if a proximal leg vein ultrasound scan cannot be carried out within 4 hours of being requested. See Management of suspected DVT for more information.

Previous changes

July 2011 — minor update. All references to the British Committee for Standards in Haematology (BCSH) guideline on oral anticoagulation with warfarin have been updated to reflect the latest guideline [Keeling et al, 2011]. Issued in September 2011.

June 2010 — minor update. The recommendation on the class of compression stockings to use to prevent the recurrence of deep vein thrombosis, or the development of post-thrombotic syndrome, has been updated. Issued June 2010.

January 2010 — minor update. Minor text change to the Basis for recommendation section on Management of suspected DVT, including clarification of why CKS recommends use of the Wells Clinical Prediction Rule in preference to other clinical prediction rules (when D-dimer testing is available in primary care). Issued in January 2010.

December 2008 to March 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations.

June 2007 — updated to include a link to the recent Patient Safety Alert from the National Patient Safety Agency (NPSA) on actions that can make anticoagulant therapy safer. Advice from the British Committee for Standards in Haematology on the management of patients on oral anticoagulants requiring dental surgery also included. Advice on managing interactions with warfarin also reformatted. Issued in June 2007.

July 2006 — minor update to include advice from the Commission on Human Medicines (CHM) regarding the potential interaction between warfarin and glucosamine. Issued in July 2006.

October–December 2005 — reviewed. Validated in March 2006 and issued in May 2006.

July 2005 — minor update to include prescribing information for compression stockings. Issued in July 2005.

July 2002 — reviewed. A scenario on Advice on risk of travel-related deep vein thrombosis was added. Validated in October 2002 and issued in December 2002.

February 2001 — reviewed to incorporate the recommendations of the Scottish Intercollegiate Guidelines Network (SIGN) guideline Antithrombotic Therapy (1999).

February 1999 — written. Validated in April 1999 and issued in August 1999.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 March 2013

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 March 2013.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Cheng, Y.J., Liu, Z.H., Yao, F.J., et al. (2013) Current and former smoking and risk for venous thromboembolism: a systematic review and meta-analysis. PLoS Medicine 10(9), e1001515. [Abstract] [Free Full-text]

Geersing, G.J., Zuithoff, N.P.A., Kearon, C., et al. (2014) Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ 348, g1340. [Free Full-text]

Sardar, P., Chatterjee, S., and Mukherjee, D. (2013) Efficacy and safety of new oral anticoagulants for extended treatment of venous thromboembolism: systematic review and meta-analyses of randomized controlled trials. Drugs 73(11), 1171-1182. [Abstract]

Schouten, H.J., Geersing, G.J., Koek, H.L., et al. (2013) Diagnostic accuracy of convention or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ 346, f2492. [Abstract] [Free Full-text]

Wasserlauf, G., Grandi, S.M., Filion, K.B., and Eisenberg, M.J. (2013) Meta-analysis of rivaroxaban and bleeding risk. American Journal of Cardiology 112(3), 454-460. [Abstract]

van der Hulle, T., Kooiman, J., den Exter, P.L., et al. (2014) Effectiveness and safety of novel oral anticoagulants compared with vitamin K-antagonists in the treatment of acute symptomatic venous thromboembolism - a systematic review and meta-analysis. Journal of Thrombosis and Haemostasis 12(3), 320-328. [Abstract]

Primary evidence

Randomized controlled trials published since the last revision of this topic:

Agnelli, G., Buller, H.R., Cohen, A., et al. (2013) Oral apixaban for the treatment of acute venous thromboembolism. New England Journal of Medicine 369(9), 799-808. [Abstract]

Kahn, S.R., Shapiro, S., Wells, P.S., et al. (2014) Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 383(9920), 880-888. [Abstract]

Schulman, S., Kakkar, A.K., Goldhaber, S.Z., et al. (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129(7), 764-772. [Abstract]

Observational studies published since the last revision of this topic:

Kamel, H., Navi, B.B., Sriram, N., et al. (2014) Risk of a thrombotic event after the 6-week postpartum period. New England Journal of Medicine epub ahead of print. [Abstract] [Free Full-text]

New policies

No new national policies or guidelines since 1 March 2013.

New safety alerts

No new safety alerts since 1 March 2013.

Changes in product availability

No changes in product availability since 1 March 2013.

Goals and outcome measures

Goals

To assess the likelihood of deep vein thrombosis (DVT) being present

To refer for same-day assessment, people who are considered to be at high risk of DVT

To manage people appropriately after discharge from hospital

Background information

Definition

What is it?

Deep vein thrombosis (DVT) is the term used to describe the formation of a thrombus (blood clot) in a deep vein, which partially or completely obstructs blood flow [National Clinical Guideline Centre, 2012a].

The thrombus can dislodge and travel in the blood, especially to the pulmonary arteries. This is known as a pulmonary embolism (PE). For more information, see the CKS topic on Pulmonary embolism.

Thrombosis usually affects the deep veins of the legs or pelvis, but may affect other sites such as the upper limbs and the intracranial and splanchnic veins [SIGN, 2010].

The National Institute for Health and Clinical Excellence (NICE) refers to DVT as provoked or unprovoked [National Clinical Guideline Centre, 2012a]:

Provoked DVT is DVT associated with a transient risk factor such as significant immobility, surgery, trauma, and pregnancy or puerperium. The combined contraceptive pill and hormone replacement therapy are also considered to be provoking risk factors. These risk factors can be removed, thereby reducing the risk of recurrence.

Unprovoked DVT is DVT occurring in the absence of a transient risk factor. The person may have no identifiable risk factor or a risk factor that is persistent and not easily correctable (such as active cancer or thrombophilia). Because these risk factors cannot be removed, the person is at an increased risk of recurrence.

The term 'venous thromboembolism' is used to describe any thromboembolic event occurring within the venous system, including DVT and PE [SIGN, 2010; McManus et al, 2011].

Incidence

How common is it?

Deep vein thrombosis has an annual incidence of about 1 in 1000 people.

[Tovey and Wyatt, 2003; Keeling et al, 2004; SIGN, 2010].

Risk factors

What are the risk factors?

Deep vein thrombosis (DVT) is more likely to occur in people with continuing or intrinsic risk factors, such as:

Previous venous thromboembolism.

Cancer (known or undiagnosed).

Age over 60 years.

Being overweight or obese.

Male sex.

Heart failure.

Severe infection [National Guideline Clearinghouse, 2012].

Acquired or familial thrombophilia.

Chronic low-grade injury to the vascular wall (for example from vasculitis, hypoxia from venous stasis, or chemotherapy).

Varicose veins [Muller-Buhl et al, 2012].

Smoking [Sweetland et al, 2013].

Risk factors that temporarily raise the likelihood of DVT include:

Immobility (for example following a stroke, operation, plaster cast, hospitalization, or during long-distance travel).

Significant trauma or direct trauma to a vein (for example intravenous catheter).

Hormone treatment (for example oestrogen-containing contraception or hormone replacement therapy).

Pregnancy and the postpartum period.

Dehydration.

[SIGN, 2010; National Clinical Guideline Centre, 2012a]

Complications

What are the complications?

The most serious complication of deep vein thrombosis (DVT) is death due to pulmonary embolism (PE).

Other complications of DVT include:

Post-thrombotic syndrome — a chronic venous hypertension causing limb pain, swelling, hyperpigmentation, dermatitis, ulcers, venous gangrene, and lipodermatosclerosis. It affects 20–40% of people after DVT of the lower limbs and can be debilitating with significant impact on quality of life. For more information, see the CKS topic on Leg ulcer - venous.

[Tovey and Wyatt, 2003; Keeling et al, 2004; National Clinical Guideline Centre, 2012a]

Diagnosis

Diagnosis of deep vein thrombosis

When to suspect DVT

When should I suspect deep vein thrombosis?

Consider the possibility of deep vein thrombosis (DVT) if typical symptoms and signs are present, especially if the person has risk factors such as previous venous thromboembolism and immobility:

Typical signs and symptoms of DVT are:

Pain and swelling in one leg, although both legs may be affected.

Tenderness, changes to skin colour and temperature, and vein distension.

Carry out a physical examination and review the person's general medical history to exclude an alternative cause for the symptoms and signs.

Use the two-level DVT Wells score to assess the likelihood of DVT and inform further management.

Basis for recommendation

Basis for recommendation

These recommendations are based mainly on a National Clinical Guideline Centre guideline (commissioned by the National institute for health and Care Excellence [NICE]): Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing [National Clinical Guideline Centre, 2012a].

The recommendation to use the Wells score as a clinical prediction guide is also supported by the Scottish Intercollegiate Guideline Network [SIGN, 2010] and other experts:

Individual symptoms and signs are, on their own, poor predictors of the presence or absence of deep vein thrombosis (DVT). The diagnosis of DVT should be made using a clinical prediction guide such as the Wells Clinical Prediction Rule, which is scored using the sum of the most sensitive and specific risk factors and signs [Goodacre et al, 2005].

A positive Homans' sign (pain in the calf or popliteal region on passive, abrupt, forceful dorsiflexion of the ankle with the knee in a flexed position) is no longer used in the assessment of DVT, as it is insensitive and nonspecific, can be painful, and there is a theoretical possibility of dislodging a thrombus [Tovey and Wyatt, 2003; Goodacre et al, 2005].

The Wells Clinical Prediction Rule (referred to as the Wells score by NICE) is a clinical tool which was originally developed in 1997 following a cohort study (n = 593) which identified the most important risk factors in people with DVT [Wells et al, 1997].

Although there are several versions of the Wells score available, NICE recommends the two-level DVT Wells score which was described in 2003 following a randomized controlled trial (RCT, n = 566) that validated the test [Wells et al, 2003]. According to NICE, compared with other versions, the two-level DVT Wells score is more relevant, up to date, and consistent with their latest understanding of venous thromboembolism risks [National Clinical Guideline Centre, 2012a].

The two-level DVT Wells score [National Clinical Guideline Centre, 2012a]:

Takes into account previous DVT, which is a major risk factor for subsequent DVT. People who had had a previous DVT were excluded from the original cohort study.

Has a simplified scoring system, allocating people to one of two groups, 'likely' or 'unlikely'. The original rules allocated people to three groups, with an additional group described as being at moderate or intermediate risk (in practice, management of this group in primary care does not differ from those who are considered to be at high risk). According to NICE, this simplified scoring system is much easier to be implemented correctly because there is less chance of confusion about what to do with the moderate group in the old system.

Has a longer duration of risk after surgery (12 weeks compared with 4 weeks in the original version).

Differential diagnosis

What else might it be?

Only about a third of people with clinical suspicion of deep vein thrombosis (DVT) have the condition. Other conditions which may present with similar signs and symptoms include:

Physical trauma, for example:

Calf muscle tear or strain.

Haematoma (collection of blood) in the muscle.

Sprain or rupture of the Achilles tendon.

Fracture.

Cardiovascular disorders, for example:

Superficial thrombophlebitis — see the CKS topic on Thrombophlebitis - superficial.

Post-thrombotic syndrome — see the CKS topic on Leg ulcer - venous.

Venous obstruction or insufficiency, or external compression of major veins (for example by a fetus during pregnancy, or cancer).

Arteriovenous fistula and congenital vascular abnormalities.

Acute limb ischaemia.

Vasculitis.

Heart failure — see the CKS topic on Heart failure - chronic.

Other conditions include:

Ruptured Baker's cyst (a Baker's cyst forms behind the knee from an out-pouching of the synovial membrane of the knee joint, and is a common complication of arthritis) — see the CKS topic on Baker's cyst.

Cellulitis (commonly mistaken as DVT) — see the CKS topic on Cellulitis - acute.

Dependent (stasis) oedema.

Lymphatic obstruction.

Septic arthritis.

Cirrhosis.

Nephrotic syndrome.

Compartment syndrome.

Basis for recommendation

Basis for recommendation

This information is from review articles [Anand et al, 1998; Gorman et al, 2000; Tovey and Wyatt, 2003] and an American guideline summary published by the US Department of Health and Human Services [National Guideline Clearinghouse, 2012].

Management

Management

Scenario: Management : covers the management of people with deep vein thrombosis.

Scenario: Management

Scenario: Management of deep vein thrombosis

192months3060monthsBoth

Management of suspected DVT

How should I manage suspected deep vein thrombosis?

Refer immediately for same-day assessment and management, if deep vein thrombosis (DVT) is suspected in a woman who is pregnant or has given birth within the past 6 weeks.

For all other people with suspected DVT, use the two-level DVT Wells score to assess the probability of a DVT.

Score one point for each of the following:

Active cancer (treatment ongoing, within the last 6 months, or palliative).

Paralysis, paresis, or recent plaster immobilization of the legs.

Recently bedridden for 3 days or more, or major surgery within the last 12 weeks requiring general or local anaesthetics.

Localized tenderness along the distribution of the deep venous system (such as the back of the calf).

Entire leg is swollen.

Calf swelling by more than 3 cm compared with the asymptomatic leg (measured 10 cm below the tibial tuberosity).

Pitting oedema (greater than on the asymptomatic leg).

Collateral superficial veins (non-varicose).

Previously documented DVT.

Subtract two points if an alternative cause is considered more likely than DVT.

The risk of DVT is likely if the score is two points or more, and unlikely if the score is one point or less.

For people who are likely to have DVT (based on the results of the two-level DVT Wells score):

Refer for a proximal leg vein ultrasound scan to be carried out within 4 hours. If a proximal leg vein ultrasound scan cannot be carried out within 4 hours of being requested:

Take a blood sample for D-dimer testing.

Give an interim 24-hour dose of a parenteral anticoagulant (note that the weight of the person will be required to calculate the dose of parenteral anticoagulant). For more information on prescribing parenteral anticoagulants, see the section on Parenteral anticoagulants in prescribing information.

Arrange for a proximal leg vein ultrasound scan (to be carried out within 24 hours of being requested).

For people who are unlikely to have DVT (based on the results of the two-level DVT Wells score), offer D-dimer testing:

If the D-dimer test is positive, refer for a proximal leg vein ultrasound scan to be carried out within 4 hours. If a proximal leg vein ultrasound scan cannot be carried out within 4 hours of being requested:

Give an interim 24-hour dose of a parenteral anticoagulant (note that the weight of the person will be required to calculate the dose of parenteral anticoagulant). For more information on prescribing parenteral anticoagulants, see the section on Parenteral anticoagulants in prescribing information.

Arrange for a proximal leg vein ultrasound scan (to be carried out within 24 hours of being requested).

If the D-dimer test is negative, consider an alternative diagnosis to explain symptoms.

Basis for recommendation

Basis for recommendation

These recommendations are based mainly on a National Clinical Guideline Centre guideline (commissioned by the National institute for health and Care Excellence [NICE]): Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing [National Clinical Guideline Centre, 2012a; NICE, 2012a], a Scottish Intercollegiate Guidelines Network (SIGN) guideline: Prevention and management of venous thromboembolism [SIGN, 2010], and an evidence-based review article produced by the British Committee for Standards in Haematology (BCSH) [Keeling et al, 2004].

Referral of pregnant and postpartum women

Referral recommendations are based on expert opinion of the Royal College of Obstetricians and Gynaecologists [RCOG, 2010]. Referral for objective testing for deep vein thrombosis (DVT) is required because it is not possible to accurately assess the risk of DVT in primary care based on the usual methods of assessment because:

The Wells Clinical Prediction Rule can not be used to assess DVT risk in pregnant women.

The usefulness of D-dimer testing is limited by a high rate of false positive results in pregnancy.

Management of suspected DVT based on results of the two-level Wells score

These recommendations are based on a guideline commissioned by NICE [NICE, 2012a].

The recommendations are also consistent with recommendations in an evidence-based American guideline which states that [Kearon et al, 2012]:

In people with a high clinical suspicion of acute VTE, treatment with parenteral anticoagulants should be commenced while awaiting the results of diagnostic tests.

In people with an intermediate clinical suspicion of acute VTE, treatment with parenteral anticoagulants should be commenced if the results of diagnostic tests are expected to be delayed for more than 4 hours.

However, in people with a low clinical suspicion of acute VTE, not treating with parenteral anticoagulants is suggested while awaiting the results of diagnostic tests provided test results are expected within 24 hours.

The Wells score

The Wells Clinical Prediction Rule (referred to as the Wells score by NICE) is a clinical tool which was originally developed in 1997 following a cohort study (n = 593) which identified the most important risk factors in people with DVT [Wells et al, 1997].

Although there are several versions of the Wells score available, NICE recommends the two-level DVT Wells score which was described in 2003 following a randomized controlled trial (RCT, n = 566) that validated the test [Wells et al, 2003]. According to NICE, compared with other versions, the two-level DVT Wells score is more relevant, up to date, and consistent with their latest understanding of VTE risks [NICE, 2012a].

The two-level DVT Wells score [NICE, 2012a]:

Takes into account previous DVT, which is a major risk factor for subsequent DVT. People who had had a previous DVT were excluded from the original cohort study.

Has a simplified scoring system, allocating people to one of two groups, 'likely' or 'unlikely'. The original rules allocated people to three groups, with an additional group described as being at moderate or intermediate risk (in practice, management of this group in primary care does not differ from those who are considered to be at high risk). NICE states that 'when a dichotomous scoring system is used (likely/unlikely), these are much easier to be implemented correctly because there is less chance of confusion about what to do with the moderate group in the old system'.

Has a longer duration of risk after surgery (12 weeks compared with 4 weeks in the original version).

D-dimer test

The formation of thrombus is normally followed by an immediate fibrinolytic response, resulting in generation of plasmin which causes the release of fibrin degradation products (predominantly containing D-dimer) into the circulation. A negative D-dimer assay therefore implies that thrombosis is not occurring and thus has a role in excluding a diagnosis of DVT (along with clinical scores and imaging). Although a positive D-dimer result can indicate thrombosis, other possible causes of a raised D-dimer include liver disease, inflammation, malignancy, pregnancy, trauma, and recent surgery [National Guideline Clearinghouse, 2012].

D-dimer tests have relatively high sensitivity but low specificity (false positive results are common). Therefore, whilst a negative D-dimer may be useful in excluding DVT, a positive D-dimer is of no diagnostic value, but merely mandates further testing.

A negative D-dimer test is good enough to exclude the diagnosis of DVT in people with an unlikely pre-test clinical probability, but it is not good enough to exclude the diagnosis of DVT in those with a likely pre-test probability.

Follow up for DVT

How should I follow up a person with confirmed deep vein thrombosis?

Provided there are no contraindications (such as pregnancy or cancer), people who have been diagnosed with deep vein thrombosis (DVT) will require maintenance treatment with an oral anticoagulant drug (warfarin or rivaroxaban) following acute treatment.

Ensure adequate monitoring — see the CKS topic on Anticoagulation - oral.

Specialists will make clinical decisions such as the choice of anticoagulant and the duration of treatment.

Treatment is usually continued for at least 3 months, but duration may be longer depending on whether the DVT was unprovoked (no obvious, transient risk factor identified) or provoked (caused by an identifiable, transient, major risk factor).

For warfarin, the usual strategy is to aim for an international normalized ratio (INR) target of 2.5, keeping within the range of 2.0–3.0. Rivaroxaban does not require any coagulation monitoring or regular dose adjustments.

Ensure that people with unprovoked DVT are investigated for the possibility of an undiagnosed cancer if they are not already known to have cancer (see Investigations for cancer for more information).

Ensure that people with unprovoked DVT have been offered thrombophilia testing, as appropriate (see Thrombophilia testing for more information).

Most people who are diagnosed with DVT require below-knee compression stockings.

Class 3 (25 mmHg to 35 mmHg) are recommended. However, class 2 stockings (18 mmHg to 24 mmHg) may be used if class 3 stockings are poorly tolerated.

Compression stockings are recommended for a duration of 2 years (unless there are contraindications). However, people with established post-phlebitic symptoms will probably benefit from ongoing use of compression stockings (that is, for more than 2 years).

A spare pair of compression stockings should be prescribed at any one time so that the person has a pair to wear when the other one is being washed.

The prescription for compression stockings should be renewed every 3–6 months or according to the manufacturer's instructions. Ideally the leg should be re-measured each time to ensure correct fit.

For more information on using compression stockings, see the CKS topic on Compression stockings.

Advise the person:

To engage in regular walking exercise after they are discharged from hospital (unless a specialist advises against this).

That the affected leg should be elevated when sitting.

That extended travel, or travel by aeroplane, should be delayed until at least 2 weeks after starting anticoagulant treatment. Travel within 2 weeks of a DVT is not recommended without seeking advice from a specialist. For more information, see the section on Recent DVT in the CKS topic on DVT prevention for travellers.

Investigations for cancer and thrombophilia testing

Investigations for cancer and thrombophilia testing

Investigation for cancer

The National Institute of Health and Clinical Excellence (NICE) recommends that people diagnosed with unprovoked deep vein thrombosis (DVT) who are not already known to have cancer should be offered the following investigations for cancer:

A physical examination (guided by the person's full history).

A chest X-ray.

Blood tests (full blood count, serum calcium, and liver function tests).

Urinalysis.

NICE advises that further investigations for cancer with an abdomino-pelvic CT scan (and a mammogram for women) should be considered in all people aged over 40 years of age with a first unprovoked DVT who do not have signs or symptoms of cancer based on initial investigation.

Thrombophilia testing

NICE recommends that if it is planned to stop anticoagulation treatment:

Testing for antiphospholipid antibodies should be considered in people who have had unprovoked DVT.

Testing for hereditary thrombophilia should be considered in people who have had unprovoked DVT and who have a first-degree relative who has had DVT.

Thrombophilia testing should not be offered:

To people who are continuing anticoagulation treatment.

To people who have had provoked DVT.

To first-degree relatives of people with a history of DVT and thrombophilia.

[National Clinical Guideline Centre, 2012a; NICE, 2012a]

Basis for recommendation

Basis for recommendation

These recommendations are based mainly on a National Clinical Guideline Centre guideline (commissioned by the National institute for health and Care Excellence [NICE]): Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing [National Clinical Guideline Centre, 2012a; NICE, 2012a] and a guideline produced by the Scottish Intercollegiate Guidelines Network: Prevention and management of venous thromboembolism [SIGN, 2010].

Anticoagulant drugs

CKS found no direct evidence from placebo controlled trials to support the use of anticoagulants in the treatment of deep vein thrombosis (DVT); however, this practice is widely accepted in clinical practice [Cundiff et al, 2006] and there is consensus across guidelines regarding the principles of treatment, although details of implementation vary [British Committee for Standards in Haematology, 2005; SIGN, 2010; National Clinical Guideline Centre, 2012a].

Usual practice is to give at least 3 months of treatment for a first venous thromboembolism (VTE) [National Clinical Guideline Centre, 2012a; NICE, 2012a; RDTC, 2012]. Following this, a decision is made on how long to continue treatment for [National Clinical Guideline Centre, 2012a; National Guideline Clearinghouse, 2012].

The National Clinical Guideline Centre found evidence suggesting that compared with 3 months treatment, 6 months oral anticoagulant treatment may be no more effective at reducing VTE related mortality, but slightly more effective at preventing recurrent VTE after treatment. Major bleeding, fatal bleeding, and intracranial bleeding were reported in the 6 months treatment groups [National Clinical Guideline Centre, 2012a].

The authors of a Cochrane systematic review (search date: October 2005) comparing long-term anticoagulation treatment with short-term treatment pointed out that whilst the absolute risk of recurrent VTE decreases with time, the harms associated with anticoagulation remain constant and are more likely with long-term treatment [Hutten and Prins, 2006].

Rivaroxaban is a direct inhibitor of activated factor X (factor Xa) indicated for the treatment of DVT, and prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT in adults [ABPI Medicines Compendium, 2013a]. It is a black triangle drug, still under intensive post-marketing surveillance by the Medicines and Healthcare products Regulatory Agency (MHRA).

Following a technology appraisal, NICE recommends rivaroxaban as an option for treating DVT after a diagnosis of acute DVT in adults [NICE, 2012b].

The Regional Drug and Therapeutic Centre state that rivaroxaban may be considered if warfarin is contraindicated or not tolerated, or if monitoring of the international normalized ratio (INR) is impractical [RDTC, 2012].

Investigations for undiagnosed cancer

This recommendation is based on NICE who state that although offering baseline tests such as physical examination, history, chest X-ray, and blood tests is associated with some costs, offering these tests has been shown to detect about half of all cancers [National Clinical Guideline Centre, 2012a].

NICE did not find any clinical trials comparing testing with no testing; however, one randomized controlled trial showed that performing these tests detects cancer in about 10% of people with a first episode of unprovoked VTE.

In addition, evidence from a large Swedish population-based study (n = 62,000) suggests that unprovoked VTE results in a significant increase in the risk of cancer within the first 1–2 years, with a standardised incidence ratio of 4.4. This is equivalent to approximately 11% of all people.

Thrombophilia testing

These recommendations are based on the expert opinion of the NICE guideline development group (GDG) after consideration of evidence for thrombophilia prevalence, relative risk of VTE recurrence for different types of thrombophilia, and effectiveness of treatment at preventing recurrences [National Clinical Guideline Centre, 2012a]. No clinical trials comparing testing with no testing were found.

Compression stockings

There is good evidence from randomized controlled trials (RCTs) that the use of compression stockings can significantly reduce the risk of a recurrent episode of DVT, especially when they are combined with other treatments (for example anticoagulants) [Sachdeva et al, 2010]. Stockings may also help prevent post-thrombotic syndrome, a possible complication of DVT.

NICE recommends graduated compression stockings with an ankle pressure greater than 23 mmHg, which most closely corresponds to British Standard class 3 stockings (25 mmHg to 35 mmHg). However, CKS recognizes that class 3 stockings are often poorly tolerated. In this instance, it is preferable to use class 2 stockings (18 mmHg to 24 mmHg), which tend to be better tolerated, rather than forego the use of stockings completely.

NICE recommends below-knee stockings because there is no evidence from RCTs about the effectiveness of thigh length stockings. Furthermore, thigh length stockings can be more difficult to fit and often roll down creating a tourniquet effect. However, they advise that clinical judgment, patient preference, and adherence should be considered when deciding on stocking length, for example some people may prefer full length stockings.

Lifestyle advice

Experts advise that an early return to walking may help reduce the risk of further DVT and improve circulation in the affected limb [SIGN, 2010; Kearon et al, 2012; National Clinical Guideline Centre, 2012a; National Guideline Clearinghouse, 2012], although there is a lack of objective evidence to prove this. Evidence from an observational study suggests that it is relatively safe, although there is a lack of evidence of efficacy.

If odema and pain are severe, return to walking may need to be deferred [Kearon et al, 2012].

CKS recommends elevating the leg whilst at rest as a comfort measure.

The British Committee for Standards in Haematology state that people with a recent DVT who are on anticoagulant treatment are at low risk of further clots but advice should be taken if flying within 2 weeks of a new DVT [British Committee for Standards in Haematology, 2005].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Parenteral anticoagulants

Parenteral anticoagulants

The parenteral anticoagulants licensed for the treatment of deep vein thrombosis are [BNF 65, 2013]:

Low molecular weight heparins (dalteparin, enoxaparin, and tinzaparin).

Fondaparinux, a synthetic pentasaccharide that inhibits activated factor X.

See the sections on Prescribing issues - dalteparin, Prescribing issues - enoxaparin, Prescribing issues - tinzaparin, or Prescribing issues - fondaparinux for more information on prescribing a 24-hour dose of these anticoagulants.

Prescribing issues - dalteparin

What should I be aware of when prescribing dalteparin?

Dalteparin should be administered subcutaneously.

The recommended dose of dalteparin for the treatment of deep vein thrombosis is:

For the single-dose injections [ABPI Medicines Compendium, 2013c; BNF 65, 2013]:

Body weight less than 46 kg — 7,500 units once daily.

Body weight 46–56 kg — 10,000 units once daily.

Body weight 57–68 kg — 12,500 units once daily.

Body weight 69–82 kg — 15,000 units once daily.

Body weight 83 kg and over — 18,000 units once daily.

Dalteparin is contraindicated [ABPI Medicines Compendium, 2013c; ABPI Medicines Compendium, 2013d]:

In people with current (or history of) heparin-induced thrombocytopenia.

In people with acute gastroduodenal ulcer; cerebral haemorrhage; known haemorrhagic diathesis (a condition causing a predisposition to bleed) or other active haemorrhage; serious coagulation disorders; acute or sub-acute septic endocarditis; haemorrhagic pericardial effusion and haemorrhagic pleural effusion; and injuries to and operations on the central nervous system, eyes, and ears.

In people who have suffered a recent (within 3 months) stroke, unless due to systemic emboli.

More detailed information on prescribing dalteparin is available in the British National Formulary (BNF) (www.bnf.org) and the relevant Summary of Product Characteristics listed in the electronic Medicines Compendium (eMC) (www.medicines.org.uk) [ABPI Medicines Compendium, 2013c; ABPI Medicines Compendium, 2013d].

Prescribing issues - enoxaparin

What should I be aware of when prescribing enoxaparin?

Enoxaparin should be administered subcutaneously.

The recommended dose of enoxaparin for the treatment of deep vein thrombosis is 1.5 mg/kg (150 units/kg) once daily [ABPI Medicines Compendium, 2013e; BNF 65, 2013].

Enoxaparin is contraindicated [ABPI Medicines Compendium, 2013e]:

In people with current (or history of) heparin-induced thrombocytopenia.

In people with acute bacterial endocarditis.

In people with active major bleeding, and conditions with a high risk of uncontrolled bleeding, including including recent haemorrhagic stroke and thrombocytopenia in people with a positive in-vitro aggregation test in the presence of enoxaparin.

In people with active gastric or duodenal ulceration.

In breastfeeding women.

More detailed information on prescribing enoxaparin is available in the British National Formulary (BNF) (www.bnf.org) and the relevant Summary of Product Characteristics listed in the electronic Medicines Compendium (eMC) (www.medicines.org.uk) [ABPI Medicines Compendium, 2013e].

Prescribing issues - tinzaparin

What should I be aware of when prescribing tinzaparin?

Tinzaparin should be administered subcutaneously.

The recommended dose of tinzaparin for the treatment of deep vein thrombosis is 175 units/kg once daily [ABPI Medicines Compendium, 2011; BNF 65, 2013].

Tinzaparin is contraindicated [ABPI Medicines Compendium, 2011]:

In people with current (or history) of heparin-induced thrombocytopenia.

In people with generalised or local haemorrhagic tendency, including uncontrolled severe hypertension; severe liver insufficiency; active peptic ulcer; acute or subacute septic endocarditis; intracranial haemorrhage; or injuries and operations on the central nervous system, eyes and ears.

In women with an impending miscarriage.

In breastfeeding women.

More detailed information on prescribing tinzaparin is available in the British National Formulary (BNF) (www.bnf.org) and the relevant Summary of Product Characteristics listed in the electronic Medicines Compendium (eMC) (www.medicines.org.uk) [ABPI Medicines Compendium, 2011].

Prescribing issues - fondaparinux

What issues should I be aware of when prescribing fondaparinux?

Fondaparinux should be administered subcutaneously.

The recommended dose of fondaparinux for the treatment of deep vein thrombosis is [ABPI Medicines Compendium, 2013b; BNF 65, 2013]:

Body weight less than 50 kg — 5 mg every 24 hours.

Body weight 50–100 kg — 7.5 mg every 24 hours.

Body weight over 100 kg — 10 mg every 24 hours.

Fondaparinux is contraindicated in people with [ABPI Medicines Compendium, 2013b]:

Active clinically significant bleeding.

Acute bacterial endocarditis.

Severe renal impairment (creatinine clearance less than 20 ml/minute).

More detailed information on prescribing fondaparinux is available in the British National Formulary (BNF) (www.bnf.org) and the relevant Summary of Product Characteristics listed in the electronic Medicines Compendium (eMC) (www.medicines.org.uk) [ABPI Medicines Compendium, 2013b].

Evidence

Evidence

Supporting evidence

Predicting who is at risk

Evidence on predicting who is at risk of deep vein thrombosis

The National Clinical Guideline Centre (commissioned by the National Institute for Health and Clinical Excellence [NICE]) reviewed the clinical and economic evidence for the effectiveness of the deep vein thrombosis (DVT) Wells score and the D-dimer test in ruling out DVT in people with suspected DVT [National Clinical Guideline Centre, 2012a; NICE, 2012a]. A summary of the evidence is presented below.

For a full version of the clinical and economic evidence, see Appendix E and Appendix F respectively in the guideline Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing: Appendices A–M (pdf) [National Clinical Guideline Centre, 2012b].

DVT Wells score

Clinical evidence

Twenty six studies (n = 13,086), of moderate quality, showed that the sensitivity for the DVT Wells score ranged from 77% to 98%, and the specificity ranged from 37% to 58%. For the purpose of ruling out DVT:

The sensitivity scores suggest that 2 to 23 out of 100 people with DVT will be missed with a DVT Wells score. This implies that the test can be considered in conjunction with another test.

The specificity scores suggest that 42 to 63 out of 100 people without DVT will be identified as having the condition. This implies that this test is not suitable for the purpose of confirming the presence of DVT without further diagnostic testing.

Limitations of the evidence included:

The wide range of sensitivity values observed; this could have been contributed by the underlying heterogeneity of the study settings and study populations.

Failure to clearly report the type of scores and scoring systems used in some studies.

The fact that most studies used the original Wells score.

Economic evidence

Economic analysis showed that using the DVT Wells scoring system is a component of a cost-effective diagnostic strategy. The cost of performing a Wells score was assumed to be equivalent to 5 minutes of hospital consultant time (£6.83) in addition to the time taken to assess the patient’s general history and conduct further examination.

The economic evidence had potentially serious limitations and partial applicability.

D-dimer test

Clinical evidence

Eight studies (rated as very low quality) involving over one thousand people showed that the sensitivity for D-dimer tests ranged from 75% to 100%, and the specificity ranged from 26% to 83%. For the purpose of ruling out DVT:

The sensitivity scores suggest that 0 to 25 of 100 people with DVT will be missed with a D-dimer test. This implies that the D-dimer test can be considered for ruling out DVT in conjunction with another test, but not on its own.

The specificity scores suggest that 17 to 74 of 100 people without DVT will be identified as having DVT. This implies that this test is not suitable for confirming the presence of DVT.

A meta-analysis identified 97 studies (rated as low quality) which showed that the 95% CI for sensitivity for all D-dimer tests ranged from 90% to 91%, and the specificity ranged from 54% to 55%. For the purpose of ruling out DVT:

The sensitivity scores suggest that 9 to 10 of 100 people with DVT will be missed with all D-dimer tests. This implies that these tests can be considered for ruling out DVT in conjunction with another test.

The specificity scores suggest that 45 to 46 of 100 people without DVT will be identified as having DVT. This implies that these tests are not suitable for confirming the presence of DVT.

The majority of the evidence base for NICE's recommendations came from a large meta-analysis which pooled 97 diagnostic studies. The main limitation of this evidence is that this is a form of 'average' sensitivity of all D-dimer tests. The actual sensitivity of tests varies between about 80% to more than 90%, depending on the specific type of technology used in the tests.

Economic evidence

Economic analysis showed that D-dimer testing is a component of a cost-effective diagnostic strategy. The cost of performing a D-dimer test was calculated as the cost of whole-blood agglutination D-dimer (£12.16) or laboratory-based D-dimer (£13.11), plus 5 minutes of hospital consultant time (£6.83).

Anticoagulants

Evidence on anticoagulants for deep vein thrombosis

CKS found no evidence from placebo-controlled trials to support the use of anticoagulants for deep vein thrombosis (DVT), and future trials are unlikely for ethical reasons. Anticoagulants are therefore recommended on the basis of their historical usage and pharmacological properties. The National Clinical Guideline Centre (commissioned by the National Institute for Health and Clinical Excellence [NICE]) found evidence that, compared with 3 months' treatment, 6 months' oral anticoagulant treatment may be no more effective at reducing venous thromboembolism (VTE) related mortality, but slightly more effective at preventing recurrent VTE after treatment. Major bleeding, fatal bleeding, and intracranial bleeding were reported in the 6 month treatment groups [National Clinical Guideline Centre, 2012a; NICE, 2012a].

Use of anticoagulants

A Cochrane systematic review (search date: May 2008) identified two RCTs (n = 113) that compared the use of an anticoagulant with a nonsteroidal anti-inflammatory drug in the treatment of DVT [Cundiff et al, 2006].

The trials were too small to determine any differences in mortality, occurrence of pulmonary emboli, or DVT progression or return between the treatment groups.

The authors estimated that future trials would require 8000 participants in order to detect a significant difference between placebo and anticoagulants in reducing the incidence of pulmonary embolism. It is unlikely that such a trial will ever be conducted for ethical reasons.

Duration of treatment

The National Clinical Guideline Centre identified eight studies comparing 3 months' oral anticoagulation treatment with 6 months' treatment in people with DVT. A summary of the results are shown in Table 1.

Evidence from cost effectiveness studies showed that the cost-effectiveness of long-term treatment depends on the type of initial VTE episode, the risk of VTE recurrence and the risk of major bleeding.

Following an initial unprovoked DVT episode, long-term treatment is not cost-effective unless the risk of VTE recurrence is increased and the risk of major bleeding is not elevated.

For a full version of the clinical and economic evidence reviewed by the National Clinical Guideline Centre, see Appendix E.8.2 and Appendix I respectively in the guideline Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing: Appendices A–M (pdf) [National Clinical Guideline Centre, 2012b].

Table 1 . Clinical summary of evidence for 6 months oral anticoagulation compared with 3 months oral anticoagulation.
Outcome 6 months 3 months Relative risk (95% CI) Absolute effect
VTE recurrence* 28/400 (7%) 32/389 (8.2%) RR 0.85 (0.52 to 1.39) 12 fewer per 1000 (from 39 fewer to 32 more)
Major bleeding* 8/380 (2.1%) 0/369 (0%) RR 16.51 (0.96 to 285) -
All cause mortality* 21/400 (5.3%) 17/389 (4.4%) RR 1.2 (0.64 to 2.24) 9 more per 1000 (from 16 fewer to 54 more)
VTE related mortality* 3/400 (0.8%) 3/389 (0.8%) RR 1.02 (0.22 to 4.8) 0 more per 1000 (from 6 fewer to 29 more)
Fatal bleeding† 2/400 (0.5%) 0/389 (0%) RR 4.86 (0.23 to 100.8) -
Intracranial bleeding† 1/380 (0.3%) 0/369 (0%) RR 2.91 (0.12 to 71.29) -
* Low quality evidence. † Very low quality evidence.
Data from: [National Clinical Guideline Centre, 2012a]

Compression stockings

Evidence on compression stockings to prevent deep vein thrombosis

There is good evidence from randomized controlled trials (RCTs) that graduated compression stockings reduce the risk of recurrent deep vein thrombosis (DVT) when used alone or with another treatment modality. Stockings may also help prevent post-thrombotic syndrome (PTS).

A Cochrane systematic review (search date: April 2010) identified 18 RCTs that investigated the effectiveness of elastic compression stockings in preventing DVT in various groups of hospitalized people [Sachdeva et al, 2010]. Compression stockings were applied on the day before surgery or on the day of surgery, and were worn up until discharge or until the person was fully mobile.

Eight RCTs (n = 1279) investigated the use of graduated compression stockings alone compared with no treatment.

In the treatment group, 86/662 people developed subsequent DVT compared with 161/617 people in the control group. This difference was significant, with an odds ratio (OR) of 0.35 (95% CI 0.26 to 0.47) favouring treatment.

This amounts to a 13% incidence of DVT in the treatment group compared with 26% in the control group.

Nine RCTs (n = 1248) investigated the use of graduated compression stockings combined with DVT prophylaxis (Dextran 70, heparin, aspirin, and sequential compression), compared with a control group (DVT prophylaxis alone).

In the combined intervention group, 26/621 people developed DVT compared with 99/627 in the control group (OR 0.25, 95% CI 0.17 to 0.36).

This amounts to a 4% incidence of DVT in the treatment group compared with 16% in the control group.

This result was reflected in another Cochrane systematic review which concluded that compared with pharmacological prophylaxis alone, the use of combined interventions significantly reduced the incidence of DVT (from 4.21% to 0.65%; OR 0.16, 95% CI 0.07 to 0.34) in high-risk people [Kakkos et al, 2008].

The authors concluded that the use of graduated compression stockings alone, or combined with other treatment, was clearly effective in preventing recurrent DVT.

The National Clinical Guideline Centre (commissioned by the National Institute for Health and Clinical Excellence [NICE]) investigated the effectiveness of graduated compression stockings in preventing PTS in people with VTE. Incidence of PTS was considered the most important outcome as this is the key contributor to morbidity and reduction of quality of life after a DVT, and severity of PTS is an important consideration [National Clinical Guideline Centre, 2012a].

In two studies (n = 374) there was a clinically important decrease in PTS in the treatment group (graduated compression stockings group) over more than 2 years (started within 1–3 weeks of DVT onset) compared with the non-treatment group (group without stockings).

No economic evidence was found; however, a simple cost analysis based on an RCT suggests that a 2-year treatment with graduated compression stockings could cost approximately £200.

For a full version of the clinical and economic evidence reviewed by the National Clinical Guideline Centre, see Appendix E.10 and Appendix F respectively in the guideline Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing: Appendices A–M (pdf) [National Clinical Guideline Centre, 2012b].

Safety of early walking after DVT

Evidence on the safety of early walking after deep vein thrombosis

There is limited evidence from observational studies to suggest that early walking following deep vein thrombosis (DVT) is a safe activity. However, there is no evidence of benefit for this activity.

A systematic review (search period not stated) identified three randomized controlled trials (RCTs), one prospective cohort study, and one retrospective cohort study, that investigated the safety of resuming walking within 1 or 2 days after DVT [Aldrich and Hunt, 2004]. Results were not combined in meta-analysis due to heterogeneity.

The three RCTs (n = 300) found no evidence of an increased (or decreased) risk of pulmonary embolism, but included only small numbers of participants and lacked statistical power.

The prospective cohort study included 1289 people admitted with symptomatic DVT.

Most people were referred because of self-reported leg symptoms, and were treated with anticoagulants, compression bandages, and immediate ambulation.

In the 10 days after starting treatment, evidence of new pulmonary embolisms (PEs) appeared in 7.4% of people with iliofemoral (proximal) DVT and 3.4% of people with calf vein (distal) DVT. The incidence of fatal PE during this period was 0.2%.

The authors concluded that walking exercise begun immediately, and compression bandages, are safe for people with DVT.

The retrospective cohort study concluded that early ambulation increased the risk for PE, but the authors of the review discounted this because of methodological problems, such as small numbers (six people with PE), and the lack of an objective diagnosis for PE.

The authors of the review cautiously concluded that there is limited evidence that early ambulation after a DVT does not increase the risk of PE.

Search strategy

Scope of search

A literature search was conducted for guidelines, randomized controlled trials and systematic reviews on the primary care management of Deep vein thrombosis.

Search dates

December 2008 - March 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Venous Thromboembolism/, exp Venous Thrombosis/, deep vein thrombosis.tw

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

British Committee for Standards in Haematology

Sources of guidelines

National Institute for Health and Clinical Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NHS Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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