Venous thromboembolic diseases: diagnosis, management and thrombophilia testing

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

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 above

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

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:
  • medicines optimisation
  • medicines adherence
  • patient experience in adult NHS services

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

• 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

• 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