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Venous thromboembolic diseases: diagnosis, management and thrombophilia testing

Key priorities for implementation

Diagnostic investigations for deep vein thrombosis

  • If a patient presents with signs or symptoms of deep vein thrombosis (DVT), carry out an assessment of their general medical history and a physical examination to exclude other causes
  • Offer patients in whom DVT is suspected and with a likely two-level DVT Wells score (see Table 1) either:
    • a proximal leg vein ultrasound scan carried out within 4 hours of being requested and, if the result is negative, a D-dimer test or
    • a D-dimer test and an interim 24-hour dose of a parenteral anticoagulant (if a proximal leg vein ultrasound scan cannot be carried out within 4 hours) and a proximal leg vein ultrasound scan carried out within 24 hours of being requested
  • Repeat the proximal leg vein ultrasound scan 6–8 days later for all patients with a positive D-dimer test and a negative proximal leg vein ultrasound scan
  • Offer patients in whom DVT is suspected and with an unlikely two-level DVT Wells score (see Table 1) a D-dimer test and if the result is positive offer either:
    • a proximal leg vein ultrasound scan carried out within 4 hours of being requested or
    • an interim 24-hour dose of a parenteral anticoagulant (if a proximal leg vein ultrasound scan cannot be carried out within 4 hours) and a proximal leg vein ultrasound scan carried out within 24 hours of being requested
Table 1: Two-level DVT Wells score*
CLINICAL FEATUREPOINTS
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 is at least as likely as DVT -2
CLINICAL PROBABILTY SIMPLIFIED SCORE
DVT likely 2 points or more
DVT unlikely 1 point or less
*Adapted with permission from Wells PS et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349: 1227–1235.

DVT=deep vein thrombosis.

Diagnosis of DVT

Diagnosis of DVT

Diagnostic investigations for pulmonary embolism

  • Offer patients in whom pulmonary embolism (PE) is suspected and with alikely two-level PE Wells score (see Table 2) either:
    • an immediate computed tomography pulmonary angiogram (CTPA) or
    • immediate interim parenteral anticoagulant therapy followed by a CTPA, if a CTPA cannot be carried out immediately
  • Consider a proximal leg vein ultrasound scan if the CTPA is negative and DVT is suspected
  • Offer patients in whom PE is suspected and with an unlikely two-level PE Wells score (see Table 2) a D-dimer test and if the result is positive offer either:
    • an immediate CTPA or
    • immediate interim parenteral anticoagulant therapy followed by a CTPA, if a CTPA cannot be carried out immediately
Table 2: Two-level PE Wells score
CLINICAL FEATUREPOINTS
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 >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 SCORE
PE likely More than 4 points
PE unlikely 4 points or less
Adapted with permission from Wells PS 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. Thrombosis and Haemostasis 2003; 83: 416–420

DVT=deep vein thrombosis, PE=pulmonary embolism.

Diagnosis of PE

Diagnosis of PE

Pharmacological interventions for deep vein thrombosis or pulmonary embolism

  • Offer a choice of low molecular weight heparin (LMWH) or fondaparinux to patients with confirmed proximal DVT or PE, taking into account comorbidities, contraindications and drug costs, with the following exceptions:
    • for patients with severe renal impairment or established renal failure (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2) offer unfractionated heparin (UFH) with dose adjustments based on the APTT (activated partial thromboplastin time) or LMWH with dose adjustments based on an anti-Xa assay
    • for patients with an increased risk of bleeding consider UFH
    • for patients with PE and haemodynamic instability, offer UFH and consider thrombolytic therapy
  • Start the LMWH, fondaparinux or UFH as soon as possible and continue it for 5 days or until the international normalised ratio (INR) (adjusted by a vitamin K antagonist [VKA]) is 2 or above for at least 24 hours, whichever is longer
  • Offer LMWH to patients with active cancer and confirmed proximal DVT or PE, and continue the LMWH for 6 months.§ At 6 months, assess the risks and benefits of continuing anticoagulation|
  • Offer a VKA beyond 3 months to patients with an unprovoked PE, taking into account the patient’s risk of VTE recurrence and whether they are at increased risk of bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment
  • Consider extending the VKA beyond 3 months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment

Thrombolytic therapy for deep vein thrombosis

  • Consider catheter-directed thrombolytic therapy for patients with symptomatic iliofemoral DVT who have:
    • symptoms of less than 14 days’ duration and
    • good functional status and
    • a life expectancy of 1 year or more and
    • a low risk of bleeding

Mechanical interventions

  • Do not offer elastic graduated compression stockings to prevent post-thrombotic syndrome or VTE recurrence after a proximal DVT. This recommendation does not cover the use of elastic stockings for the management of leg symptoms after DVT

Investigations for cancer

  • Consider further investigations for cancer with an abdomino-pelvic CT scan (and a mammogram for women) in all patients aged over 40 years with a first unprovoked DVT or PE who do not have signs or symptoms of cancer based on initial investigation

§ At the time of publication (June 2012) some types of LMWH do not have a UK marketing authorisation for 6 months of treatment of DVT or PE in patients with cancer. Prescribers should consult the summary of product characteristics for the individual LMWH and make appropriate adjustments for severe renal impairment or established renal failure. Informed consent for off-label use should be obtained and documented

| Although this use is common in UK clinical practice, at the time of publication (June 2012), none of the anticoagulants has a UK marketing authorisation for the treatment of DVT or PE beyond 6 months in patients with cancer. Informed consent for off-label use should be obtained and documented

Prescribers should refer to specific product information and contraindications before offering graduated compression stockings.

© NICE 2015. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Available from: www.nice.org.uk/guidance/CG144. All rights reserved. Subject to Notice of rights.

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. 

First included: October 2012, updated December 2015