Diagnosis and Treatment of Venous Thromboembolism

For suspected venous thromboembolism (VTE) in pregnant patients, refer to separate guideline here

This guideline relates to both inpatient and outpatient management of non-pregnant adult patients with suspected lower limb deep vein thrombosis (DVT) and/ or pulmonary embolism (PE). For guidance on thrombolysis for high risk PE, refer to AthenA.

Introduction

Venous thromboembolism (VTE) can present at many anatomical sites but most commonly in the deep veins of the lower limbs (Deep Vein Thrombosis – DVT) or embolised to the pulmonary arteries (Pulmonary Embolism – PE).

This guideline does not cover the less common VTE presentations such as Upper limb DVT, Portal Vein Thrombosis, or Venous Sinus Thrombosis.

While most VTE present in the community with referral to hospital, hospitalised patients are at increased risk of VTE, so a significant number of VTE events occur in patients already hospitalised for another reason.

The evidence available to guide clinical assessment and risk stratification for likelihood of VTE, including D-dimer measurement, are based on community presentation and therefore should not be applied to hospitalised patients suspected of VTE. For hospitalised patients clinical suspicion alone should trigger consideration of anticoagulation and imaging to achieve a definitive diagnosis.

D-Dimer

As of 2019, NHS Ayrshire & Arran have adopted age-adjusted D-dimer. For patients over the age of 50 years old, the patients’ age should be multiplied by 10 and this value should be used as the positive cut-off value for the patient’s D-dimer.

For example, a patient aged 73, should be deemed to have a positive D-dimer if it equals 730ng/mL or more. This has to be considered and applied by the individual clinician.

Diagnosis of suspected lower limb DVT

Flowchart for managing 1st presentation of suspected lower limb DVT in non-pregnant adult ≥ 18 year old patients can be found in the link below. The Revised Wells Score for DVT can be found in Table 1 to assist in the use of the flowchart.

Table 1 – Revised Wells Score for DVT

Patient variable Points
Active cancer with ongoing treatment or treatment within the previous 6 months or palliative care 1
Paralysis, paresis or recent immobilisation of the legs in plaster 1
Recently confined to bed for more than 3 days or major surgery within 12 weeks requiring general or regional anaesthetic 1
Tenderness along the distribution of the deep venous system 1
Whole leg swollen 1
Calf swelling by more than 3cm compared to asymptomatic leg (measured 10cm below the tibial tuberosity) 1
Pitting oedema more marked in the symptomatic leg 1
Collateral superficial veins, not varicose veins 1
Previously documented deep vein thrombosis 1
Alternative diagnosis as likely or more likely than DVT -2

TOTAL:

Score <2: DVT unlikely

Score ≥2: DVT likely

  
Wells et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349(13):1227-35.
Copyright permission sought via NHS Scotland (February 2025).

Diagnosis of suspected PE

Flowchart for managing 1st presentation of suspected PE in non-pregnant adult ≥ 18 year old patients can be found in the link below. The Two Tiered Wells Score for PE can be found in Table 2 to assist in the use of the flowchart. And guidance on the use of the Pulmonary Embolism Severity Index (PESI) score in the management of patients via an ambulatory pathway is found in Table 3 below.

Table 2 – The Two Tiered Wells Score for PE

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 score

Score ≤4 points: PE unlikely

Score >4 points: PE likely

  
Wells et al. Derivation of a simple clinical model to categorize patient's probability of pulmonary embolism: increasing the model's utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83(3):416-20.
Copyright permission sought via NHS Scotland (February 2025).

Patients with a lower risk PESI score (≤85) can be managed safely and effectively as an outpatient following diagnosis of PE. The decision to manage such patients via an ambulatory pathway should be taken by an appropriately trained senior clinical decision maker, ideally following discussion with a consultant.

The PESI score (see table 3 below) is based on 11 patient variables and accurately predicts the risk of mortality at 30 days.

Table 3 – The Pulmonary Embolism Severity Index (PESI)

Patient variable Points
Age Age in years
Male sex 10
History of cancer 30
History of heart failure 10
History of chronic lung disease 10
Pulse ≥110 beats/minute 20
Systolic blood pressure <100mmHg 30
Respiratory rate ≥30 breaths/minute 20
Temperature <36oC 20
Altered mental status (defined as disorientation, lethargy, stupor or coma) 60
Arterial oxygen saturation <90% (with or without supplemental oxygen) 20

TOTAL SCORE:

  
Aujesky et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;15;172(8):1041-6.
Copyright permission sought via NHS Scotland (February 2025).

General management

Duration of anticoagulation

  • Consider stopping anticoagulation after 3 months if the provoking* factor is no longer present and the course has been uncomplicated; for PE this will usually be reviewed at Respiratory clinic and patients should remain on anticoagulation until then. Advise patients on the risk of recurrence, signs and symptoms to look out for and information on how they can seek further assessment.
  • Consider continuing anticoagulation beyond 3 months based on their risk of bleeding (which can be estimated using the HASBLED score), risk of VTE recurrence and patient preferences. For patients with a low risk of bleeding and unprovoked DVT/PE, the benefits of continued anticoagulation will often outweigh the risk. Discuss stopping anticoagulation if the HASBLED score is greater than 4 and cannot be modified.
  • The benefits of lifelong anticoagulation may need to be reviewed if the clinical situation changes or if the patient develops other diagnoses.

*N.B. Provoked DVT or PE in a patient with an antecedent (within 3 months) and transient major clinical risk factor for VTE – for example surgery, trauma, significant immobility (bedbound, unable to walk unaided or likely to spend a substantial proportion of the day in bed or in a chair), pregnancy or puerperium – or in a patient who is having hormonal therapy (oral contraceptive or hormone replacement therapy). [NICE 158, Aug 2023]

Follow-up

Consider referring patients with a first presentation of unprovoked DVT to the DVT MDT to discuss duration of treatment if it is felt this may alter management.

The majority of patients with PE should be followed up by Respiratory Medicine, unless they would not be investigated for pulmonary hypertension (i.e. terminal illness). They should be referred to Respiratory on discharge, with clinic follow-up at 3 months (while still on anticoagulation). An echocardiogram (ECHO) at 2 months from discharge is recommended for patients with previous VTE who are being referred for Respiratory follow-up as this is associated with increased risk of chronic thromboembolic pulmonary hypertension (CTEPH).

Special patient groups where management may differ include:

Renal disease

      • Apixaban is contraindicated in patients with CrCl <15ml/min. Apixaban should be used with caution in patients with CrCl 15-30ml/min and therefore warfarin may be a more suitable choice.
      • Anticoagulation in significant CKD should be discussed with a pharmacist and/or Haematologist/Renal physician.
      • Renal dialysis patients should be treated with dalteparin or warfarin depending on patient preference. Treatment of DVT/PE for renal dialysis patients must be discussed with the patient’s Consultant Nephrologist.

Patients with active malignancy

      • For patients with active cancer and a confirmed proximal DVT or PE, consider treatment with a DOAC.
      • Take into account tumour site (e.g. GI or GU bleeding risk), concurrent systemic anti-cancer treatment and bleeding risk when considering the choice of anticoagulant.
      • Where a DOAC is unsuitable, consider treatment with LMWH or warfarin (with LMWH bridging until therapeutic).
      • Treatment duration should be reviewed at 3-6 months and the need for ongoing anticoagulation can be decided in conjunction with Oncology/their parent specialty.

Drug interactions

      • Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inducers of CYP3A4 and P-gp, such as rifampicin, carbamazepine, phenytoin, phenobarbital or St. John's wort, as the efficacy of apixaban may be compromised.
      • Apixaban is also not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp such as ketoconazole, itraconazole, voriconazole, posaconazole and HIV protease inhibitors such as ritonavir due to a significantly increased plasma apixaban concentration and greater risk of adverse effects such as bleeding.
      • In such patients, Warfarin or LMWH should be used for the treatment of DVT or PE, or prophylaxis of recurrent VTE.
      • For further information on interactions with apixaban and other medicines please refer to the manufacturers Summary of Product Characteristics (SPC).

Antiphospholipid syndrome

      • Current evidence does not support use of DOAC in patients with VTE and established antiphospholipid syndrome. There may be an increased risk of thrombotic events whilst taking DOAC (compared to warfarin).
      • Warfarin is the recommended anticoagulant for this group. These cases should also be discussed with the Haematology team.

Recurrent VTE

      • Patients with recurrent VTE can be treated with warfarin or apixaban. Both can be prescribed according to clinical / patient preference.
      • After 6 months of apixaban 5 mg orally twice daily the dose should be reduced to 2.5 mg orally twice daily and taken lifelong.
      • If a further DVT/PE occurs whilst being treated with warfarin or apixaban, please seek specialist advice from a Consultant Haematologist.

Intravenous Drug Users

Extremes of weight (<50kg, >150kg) 

Anticoagulation in extremes of weight or in significant CKD should be discussed with a pharmacist and/or Haematologist / Renal physician.

Patients with superficial thrombophlebitis

For management of patients with superficial thrombophlebitis, please see here.

Drug therapy / treatment options

N.B. Anticoagulation carries a bleeding risk. Assess the patients bleeding risk using a validated scoring system, e.g. HASBLED, and thorough history.

Dalteparin (subcutaneous LMWH)

Dalteparin is an appropriate first line treatment for suspected VTE.

Dalteparin is administered subcutaneously, once daily according to the weight ranges in table 4 below. The single daily dose must not exceed 18,000 units.

Table 4 – Dalteparin dosing

Actual weight (kg) Dalteparin daily dose (units) using pre-filled syringes Dalteparin Syringe Colour
<46kg 7,500 units once daily Green
46–56kg 10,000 units once daily Red
57–68kg 12,500 units once daily Brown
69–82kg 15,000 units once daily Purple
≥83kg 18,000 units once daily Grey

NOTES

  • If dalteparin treatment is contra-indicated, then consider treatment with DOAC or intravenous unfractionated heparin (see here).
  • Treatment should start whilst the results of investigations are awaited. A baseline FBC (platelets) should be checked in all patients and then re-checked after 1 day. If platelets are <100 x109 at baseline, discuss anticoagulation plan with a Consultant Haematologist.
  • Heparin Induced Thrombocytopenia (HIT) is an uncommon complication of treatment with Dalteparin which may present with thrombocytopenia (platelet fall of 50% from baseline or <100 x109), new thrombosis or skin allergy. If HIT is suspected or if platelets fall below 100 x109 contact a Consultant Haematologist for further advice.
  • If there is concern about active bleeding, discuss urgent investigations with the duty radiologist prior to treatment.
  • Dosing in renal impairment (eGFR<30ml/min): Reduce the dose of dalteparin by approximately 20%. The patient should receive the dose one below that recommended for their weight on table 4 above i.e. a 60kg patient should receive 10,000 units instead of 12,500 units. It should be used for as short a time as possible. Normal doses can be used for a maximum of about 48 hours if the benefit outweighs the risk.
  • Refer to ADTC 75 Administration Guide: Dalteparin pre-filled single dose syringes for treatment of DVT and PE (link only active if accessing via NHS network) for further information, including dosing in patients with solid tumours beyond 1 month and discharge planning.

Apixaban

Suspected VTE

  • Apixaban can be considered for anticoagulation in ‘suspected’ VTE. This is particularly useful in low risk groups where ambulatory management is used.
  • DOAC should not be used in suspected VTE if there are any concerns about swallowing, vomiting or absorption.
  • Other considerations must consider whether the patient is at an extreme of body weight, has PE with haemodynamic instability, or belongs to one of the special patient groups discussed below.

Confirmed VTE

  • The preferred oral anticoagulant for confirmed VTE is apixaban - however some patient groups may be unsuitable for treatment with apixaban including:
    patients with CrCl <30ml/min, patients on drugs that may interact with apixaban,
    patients with antiphospholipid syndrome and patients with active cancer, see below under special patient groups.

Patients with acute PE and/or DVT deemed suitable for apixaban therapy:

  • If using dalteparin initially, apixaban treatment should be started 24 hours after
    last LMWH dose.
  • For the treatment of DVT/PE, give apixaban oral 10mg twice daily for the first 7 days and then 5mg twice daily
  • For dosing in renal impairment (see below and refer to SPC):
    • CrCl 15-29 ml/min: Use with caution. Warfarin may be a suitable alternative.
    • CrCl <15 ml/min: Avoid. If treatment with apixaban requires to be considered then discuss with a Consultant Nephrologist first.
  • Patients should be counselled prior to starting apixaban. They should be provided with a copy of the patient information leaflet and the manufacturer’s patient alert card should be completed.
  • The patient should be aware of the ongoing monitoring arrangements and should be provided with advice about what to do if bleeding occurs.
  • They should also be advised about what to do if they miss a dose of apixaban
    and who to contact for further advice.

Missed doses of apixaban

  • 10mg twice daily phase (day 1 - 7): If a patient misses a dose during the 10mg
    twice daily treatment phase (day 1 - 7), the dose should be taken immediately to
    ensure intake of 20mg per day (four 5mg tablets may be taken at once). Thereafter, the patient should take the next dose at the normal time the following day and continue taking 10mg twice daily until dose reduction after 7 days.
  • 5mg twice daily maintenance phase: If a dose is missed from day 7 onwards,
    the dose should be taken immediately, to ensure a total daily dose of 10mg per
    day. Thereafter, the patient should take the next dose at the normal time the following day and continue taking 5 mg twice daily. 

Stockings

Stockings are not currently recommended for prevention of post-thrombotic syndrome in patients who present with DVT. They should be considered with patients who have superficial thrombophlebitis if no contraindications (see here).

 

Guideline reviewed June 2024
Page updated April 2025



;