Venous thromboembolic diseases: diagnosis, management and thrombophilia testing

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Overview

This Guidelines summary covers diagnosis and initial management, outpatient treatment for low-risk pulmonary embolism (PE), anticoagulation treatment for suspected or confirmed deep vein thrombosis (DVT) or PE, and information and support for people having anticoagulation treatment
This summary only covers key recommendations for primary care. For a complete set of recommendations, see the full guideline

This summary has been abridged for print. View the full summary at guidelines.co.uk/455308.article.

Diagnosis and initial management

Signs or symptoms of DVT

For people who present with signs or symptoms of DVT, such as a swollen or painful leg, assess their general medical history and do a physical examination to exclude other causes
If DVT is suspected, use the 2-level DVT Wells score (Table 1) to estimate the clinical probability of DVT

Table 1: Two-level DVT Wells score

Clinical feature	Points
Active cancer (treatment ongoing, within 6 months, or palliative)	1
Paralysis, paresis or recent plaster immobilisation of the lower extremities	1
Recently bedridden for 3 days or more, or major surgery within 12 weeks requiring general or regional anaesthesia	1
Localised tenderness along the distribution of the deep venous system	1
Entire leg swollen	1
Calf swelling at least 3 cm larger than asymptomatic side	1
Pitting oedema confined to the symptomatic leg	1
Collateral superficial veins (non-varicose)	1
Previously documented DVT	1
An alternative diagnosis is at least as likely as DVT	-2
Clinical probability simplified score
DVT likely	2 points or more
DVT unlikely	1 point or less
Adapted with permission from Wells et al. (2003) Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis DVT=deep vein thrombosis.

Suspected DVT—diagnosis and initial management. Download a PDF of this algorithm

DVT likely (Wells score 2 points or more)

Offer people with a likely DVT Wells score (2 points or more):
- a proximal leg vein ultrasound scan, with the result available within 4 hours if possible
- a D-dimer test if the scan result is negative
If a proximal leg vein ultrasound scan result cannot be obtained within 4 hours, offer people with a DVT Wells score of 2 points or more:
- a D-dimer test, then
- interim therapeutic anticoagulation and
- a proximal leg vein ultrasound scan with the result available within 24 hours
For people with a positive proximal leg vein ultrasound scan:
- offer or continue anticoagulation treatment or
- if anticoagulation treatment is contraindicated, offer a mechanical intervention
For people with a negative proximal leg vein ultrasound scan and a positive D-dimer test result:
- stop interim therapeutic anticoagulation
- offer a repeat proximal leg vein ultrasound scan 6 to 8 days later and
  - if the repeat scan result is positive, follow the actions above
  - if the repeat scan result is negative, follow the actions below
For people with a negative proximal leg vein ultrasound scan and a negative D-dimer test result:
- stop interim therapeutic anticoagulation
- think about alternative diagnoses
- tell the person that it is not likely they have DVT. Discuss with them the signs and symptoms of DVT and when and where to seek further medical help

DVT unlikely (Wells score 1 point or less)

Offer people with an unlikely DVT Wells score (1 point or less):
- a D-dimer test with the result available within 4 hours or
- if the D-dimer test result cannot be obtained within 4 hours, offer interim therapeutic anticoagulation while awaiting the result
If the D-dimer test result is negative, follow the actions above
If the D-dimer test result is positive, offer:
- a proximal leg vein ultrasound scan, with the result available within 4 hours if possible or
- interim therapeutic anticoagulation and a proximal leg vein ultrasound scan with the result available within 24 hours
If the proximal leg vein ultrasound scan is:
- positive, follow the actions above
- negative, follow the actions abo ve

D-dimer testing

When offering D-dimer testing for suspected DVT or PE, consider a point-of-care test if laboratory facilities are not immediately available
If using a point-of-care D-dimer test, choose a fully quantitative test
When using a point-of-care or laboratory D-dimer test, consider an age-adjusted D-dimer test threshold for people aged over 50

Signs or symptoms of PE

For people who present with signs or symptoms of PE, such as chest pain, shortness of breath or coughing up blood, assess their general medical history, do a physical examination and offer a chest X-ray to exclude other causes

Pulmonary embolism rule-out criteria (the PERC rule)

If clinical suspicion of PE is low^[^A^], consider using the pulmonary embolism rule-out criteria (PERC) to help determine whether any further investigations for PE are needed
If PE is suspected, use the 2-level PE Wells score (Table 2) to estimate the clinical probability of PE

Table 2: Two-level PE Wells score

Clinical feature	Points
Clinical signs and symptoms of DVT (minimum of leg swelling and pain with palpation of the deep veins)	3
An alternative diagnosis is less likely than PE	3
Heart rate more than 100 beats per minute	1.5
Immobilisation for more than 3 days or surgery in the previous 4 weeks	1.5
Previous DVT/PE	1.5
Haemoptysis	1
Malignancy (on treatment, treated in the last 6 months, or palliative)	1
Clinical probability simplified scores
PE likely	More than 4 points
PE unlikely	4 points or less
Adapted with permission from Wells et al. (2000) Derivation of a simple clinical model to categorize patients’ probability of pulmonary embolism: increasing the model’s utility with the SimpliRED D-dimer PE=pulmonary embolism.

Suspected PE—diagnosis and initial management. Download a PDF of this algorithm

PE likely (Wells score more than 4 points)

For people with a likely PE Wells score (more than 4 points):
- offer a computed tomography pulmonary angiogram (CTPA) immediately if possible or
- for people with an allergy to contrast media, severe renal impairment (estimated creatinine clearance^[^B^] less than 30 ml/min) or a high risk from irradiation, assess the suitability of a ventilation/perfusion single photon emission computed tomography (V/Q SPECT) scan or, if a V/Q SPECT scan is not available, a V/Q planar scan, as an alternative to CTPA
  
  If a CTPA, V/Q SPECT or V/Q planar scan cannot be done immediately, offer interim therapeutic anticoagulation (see the section on interim therapeutic anticoagulation for suspected DVT or PE)

If PE is identified by CTPA, V/Q SPECT or V/Q planar scan:
- offer or continue anticoagulation treatment or
- if anticoagulation treatment is contraindicated, consider a mechanical intervention
  
  For people with PE and haemodynamic instability see the full guideline section on thrombolytic therapy

If PE is not identified by CTPA, V/Q SPECT or V/Q planar scan:
- consider a proximal leg vein ultrasound scan if DVT is suspected
- if DVT is not suspected:
  - stop interim therapeutic anticoagulation
  - think about alternative diagnoses
  - tell the person that it is not likely they have PE. Discuss with them the signs and symptoms of PE and when and where to seek further medical help

PE unlikely (Wells score 4 points or less)

Offer people with an unlikely PE Wells score (4 points or less):
- a D-dimer test with the result available within 4 hours if possible or
- if the D-dimer test result cannot be obtained within 4 hours, offer interim therapeutic anticoagulation while awaiting the result
  
  If the D-dimer test result is:
- positive, follow the actions above
- negative:
  - stop interim therapeutic anticoagulation
  - think about alternative diagnoses
- tell the person that it is not likely they have PE. Discuss with them the signs and symptoms of PE and when and where to seek further medical help

Signs or symptoms of both DVT and PE

For people who present with signs or symptoms of both DVT and PE, carry out initial diagnostic investigations for either DVT or PE, basing the choice of diagnostic investigations on clinical judgement

Outpatient treatment for low-risk PE

Consider outpatient treatment for suspected or confirmed low-risk PE, using a validated risk stratification tool to determine the suitability of outpatient treatment
When offering outpatient treatment to people with suspected PE, follow recommendations on diagnosis and initial management
When offering outpatient treatment to people with confirmed PE, follow the recommendations in the section on anticoagulation treatment for confirmed DVT or PE
Agree a plan for monitoring and follow-up with people having outpatient treatment for suspected or confirmed low-risk PE. Give them:
- written information on symptoms and signs to look out for, including the potential complications of thrombosis and of treatment
- direct contact details of a healthcare professional or team with expertise in thrombosis who can discuss any new symptoms or signs, or other concerns
- information about out-of-hours services they can contact when their healthcare team is not available

Anticoagulation treatment for suspected or confirmed DVT or PE

When offering anticoagulation treatment follow the recommendations on shared decision making and supporting adherence in the NICE guidelines on:

Interim therapeutic anticoagulation for suspected DVT or PE

Follow the recommendations on when to offer interim therapeutic anticoagulation for suspected proximal DVT or PE in the section on diagnosis and initial management
If possible, choose an interim anticoagulant that can be continued if DVT or PE is confirmed^[^C^]
When using interim therapeutic anticoagulation for suspected proximal DVT or PE:
- carry out baseline blood tests including full blood count, renal and hepatic function, prothrombin time (PT) and activated partial thromboplastin time (APTT)
- do not wait for the results of baseline blood tests before starting anticoagulation treatment
- review, and if necessary act on, the results of baseline blood tests within 24 hours of starting interim therapeutic anticoagulation

Anticoagulation treatment for confirmed DVT or PE

Offer anticoagulation treatment for at least 3 months to people with confirmed proximal DVT or PE. For recommendations on treatment after 3 months see the full guideline section on long-term anticoagulation for secondary prevention
If not already done, carry out baseline blood tests when starting anticoagulation treatment
When offering anticoagulation treatment, take into account comorbidities, contraindications and the person’s preferences

Follow the recommendations (in the full guideline) on anticoagulation treatment in the sections on:

DVT or PE in people at extremes of body weight
PE with haemodynamic instability
DVT or PE with renal impairment or established renal failure (also see below)
DVT or PE with active cancer
DVT or PE with triple positive antiphospholipid syndrome
Offer either apixaban or rivaroxaban to people with confirmed proximal DVT or PE (but see recommendations 1.3.11 to 1.3.20 in the full guideline for people with any of the clinical features listed here). If neither apixaban nor rivaroxaban is suitable offer:
- low molecular weight heparin (LMWH) for at least 5 days followed by dabigatran or edoxaban or
- LMWH concurrently with a vitamin K antagonist (VKA) for at least 5 days, or until the INR is at least 2.0 in 2 consecutive readings, followed by a VKA on its own
Do not routinely offer unfractionated heparin (UFH) with a VKA to treat confirmed proximal DVT or PE unless the person has renal impairment or established renal failure (see Anticoagulation treatment for DVT or PE with renal impairment or established renal failure, below) or an increased risk of bleeding
Do not routinely offer self-management or self-monitoring of INR to people who have had DVT or PE and are having treatment with a VKA

Anticoagulation treatment for DVT or PE with renal impairment or established renal failure

Offer people with confirmed proximal DVT or PE and renal impairment (estimated creatinine clearance^[^B^] between 15 ml/min and 50 ml/min) one of:
- apixaban
- rivaroxaban
- LMWH^[^D^] for at least 5 days followed by:
  - edoxaban or
  - dabigatran if estimated creatinine clearance is 30 ml/min or above
- LMWH^[^D^] or UFH, given concurrently with a VKA for at least 5 days or until the INR is at least 2.0 in 2 consecutive readings, followed by a VKA on its own
  
  Note the cautions and requirements for dose adjustment and monitoring in the medicine’s SPC, and follow locally agreed protocols or advice from a specialist or multidisciplinary team
Offer people with confirmed proximal DVT or PE and established renal failure (estimated creatinine clearance^[^B^] less than 15 ml/min) one of:
- LMWH^[^D^]
- UFH
- LMWH or UFH concurrently with a VKA for at least 5 days or until the INR is at least 2.0 in 2 consecutive readings, followed by a VKA on its ownNote the cautions and requirements for dose adjustment and monitoring in the medicine’s SPC, and follow locally agreed protocols or advice from a specialist or multidisciplinary team

Treatment failure

If anticoagulation treatment fails:
- check adherence to anticoagulation treatment
- address other sources of hypercoagulability
- increase the dose of anticoagulant or change to an anticoagulant with a different mode of action

Information and support for people having anticoagulation treatment

Give people having anticoagulation treatment verbal and written information about:
- how to use anticoagulants
- how long to take anticoagulants
- possible side-effects of anticoagulants and what to do if these occur
- how other medications, foods and alcohol can affect oral anticoagulation treatment
- any monitoring needed for their anticoagulant treatment
- how anticoagulants may affect their dental treatment
- taking anticoagulants if they are planning pregnancy or become pregnant
- how anticoagulants may affect activities such as sports and travel
- when and how to seek medical help
Give people who are having anticoagulation treatment information and an ‘anticoagulant alert card’ that is specific to their treatment. Advise them to carry the ‘anticoagulant alert card’ at all times
Be aware that heparins are of animal origin and that apixaban and rivaroxaban contain lactose from cow’s milk. For people who have concerns about using animal products because of a religious or ethical belief, or a food intolerance, see the section on giving information and planning for discharge in the NICE guideline on venous thromboembolism in over 16s

Mechanical interventions

Elastic graduated compression stockings

Do not offer elastic graduated compression stockings to prevent post-thrombotic syndrome or VTE recurrence after a DVT. This recommendation does not cover the use of elastic stockings for the management of leg symptoms after DVT
If offering elastic graduated compression stockings to manage leg symptoms after DVT, explain how to apply and use them, how long they should be worn and when they should be replaced

Footnotes

[A] The clinician estimates the likelihood of PE to be less than 15% based on the overall clinical impression and other diagnoses are feasible

[B] Estimated creatinine clearance using the Cockcroft and Gault formula; see the BNF’s prescribing in renal impairment

[C] At the time of publication (March 2020) direct-acting anticoagulants and some low molecular weight heparins do not have a UK marketing authorisation for the treatment of suspected DVT or PE. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information

[D] At the time of publication (March 2020) some low molecular weight heparins do not have a UK marketing authorisation for the treatment of DVT or PE in people with severe renal impairment (estimated creatinine clearance 15 ml/min to 30 ml/min) or established renal failure (estimated creatinine clearance less than 15 ml/min). The prescriber should consult the medicine’s summary of product characteristics for details, and follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information

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NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication

Published date: 26 March 2020.