Diagnosis

The GDG recommended moving from a three-way (low, medium and high probability) to two-way Wells score for DVT and PE and if these are deemed likely then proceeding to diagnostic imaging, with compression Doppler ultrasound of the leg veins and CT pulmonary angiography (CTPA), respectively, as the modality of choice. For DVT, if the first ultrasound scan is negative, then further risk stratification with d-dimer should be undertaken, and if positive, the patient re-scanned. When there is concern about the risk of radiation, contrast allergy or renal impairment, nuclear medicine ventilation-perfusion (VQ) scanning is an alternative, preferably using single photon emission CT (SPECT), but planar if not available. When CTPA or VQ is negative and a DVT is suspected, further imaging of the leg veins with ultrasound is recommended. Ultrasound of the leg veins is not recommended as a first-line imaging investigation in patients presenting with symptoms and/or signs of PE and DVT. In the presence of a low likelihood of DVT or PE using the Wells score, then d-dimer stratification is advised. Positive assays necessitate further imaging, whereas an alternative diagnosis should be sought in patients with negative assays. Previous guidelines2 ,3 have advocated the use of echocardiography to diagnose PE when the patient's condition is unstable and rapid intervention is required. This issue is not covered by the GDG.

Treatment

Patients should be offered treatment if imaging is not available immediately in the case of PE or within 4 h for suspected DVT. Once the diagnosis has been confirmed then anticoagulation should be commenced with subcutaneous low molecular weight heparin (LMWH) or fondaparinux for at least 5 days or until an international normalised ratio (INR) of >2 is achieved with a vitamin K antagonist (VKA). In the presence of renal impairment (estimated glomerular filtration rate <30 ml/min/1.73 m²), either unfractionated heparin or LMWH with anti-factor Xa monitoring should be used and when there is a risk of bleeding, unfractionated heparin is advised. Patients with active malignancy should receive LMWH (see section below for duration).

One of the more stand-out recommendations is the advice to perform catheter-directed thrombolysis for symptomatic ilio-femoral DVT when it has been present for up to 14 days in patients with good function, low risk of bleeding and a life expectancy of more than 1 year. The principal driving factor for this recommendation was from studies of systemic and catheter-directed thrombolysis showing a reduction in post-thrombotic syndrome (PTS), with a lower risk of bleeding with catheter-directed versus systemic administration, although it was deemed low-quality evidence.

In recent guidelines from learned societies,2 ,3 PE has been risk stratified into three categories, low, medium or high, or non-massive, sub-massive and massive PE. However, the GDG felt that there was insufficient evidence to justify different treatment strategies for these three groups and thus suggested only classifying patients as having haemodynamic stability or instability, as defined by systolic blood pressure <90 mm Hg or a pressure drop of ≥40 mm Hg for >15 min if not caused by an arrhythmia, hypovolaemia or sepsis. A positive recommendation was made for the use of unfractionated heparin and subsequent systemic thrombolysis for the treatment of haemodynamically unstable PE, but not catheter-directed thrombolysis. However, the GDG recognised that there was a potentially important increased risk of major bleeding. There was insufficient evidence to recommend thrombolysis to stable patients, such as those with documented right ventricular dysfunction.

When there is a contraindication to anticoagulation or thrombolysis due to bleeding risk, inferior vena cava filter placement is recommended, with a plan for removal once anticoagulation can safely commence, but no recommendation was given regarding the role of mechanical clot disruption or surgical embolectomy, in the absence of adequate data to review. Filter insertion was also suggested when recurrent PE is diagnosed despite anticoagulation with an increased INR target range of 3–4 or the use of LMWH.

Lastly, for patients with a diagnosis of DVT, below knee ipsilateral graduated compression stockings (>23 mm Hg) are recommended for the prevention of post-thrombotic syndrome, at least 1 week after treatment has begun or once leg swelling has subsided. Patients should continue to use these for 2 years and they should be re-fitted twice or three times a year.

Duration of treatment and role of thrombophilia testing

For patients with a clear temporary provoking risk factor for VTE, anticoagulation is recommended for a period of 3 months. If the patient has active cancer, they should receive treatment with LMWH for 6 months before reviewing the decision to continue anticoagulation with a VKA. For unprovoked events, a decision whether to continue or discontinue anticoagulation should be made at 3 months. This decision should be taken after discussion with the patient, having taken in to account the long-term risk of bleeding and risk of recurrence. The GDG felt that the recommendation for long-term anticoagulation following PE was stronger than following DVT, since the risk of the recurrent event being a PE, and thus carrying greater morbidity and mortality, is greater if the primary event is a PE. The complexity of this decision-making process usually requires it to be made in the secondary care setting. The decision should then be reviewed annually since relative risks and circumstances may change. No guidance is provided on how to assess this balance, since it was felt by the GDG that no rule of thumb or validated tool exists to assess risk.

In recognising that the presence of thrombophilia does not predict the risk of recurrence following an unprovoked episode of VTE, the GDG were mindful to reduce the rate of unnecessary thrombophilia investigations and provide clear guidance on when it may impact on treatment decisions. As such, the only clear indications to perform thrombophilia testing were when consideration was being given to discontinuing anticoagulation following an unprovoked DVT or PE. Patients with a history of a first-degree relative with VTE should undergo testing for hereditary thrombophilia, but testing should not be extended to relatives, and all patients should undergo testing for antiphospholipid antibodies (detected as a lupus anticoagulant or as antibodies against cardiolipin or β2-glycoprotein I).

Lastly, the GDG stressed the importance of patient information and education relating to lifestyle issues while on anticoagulation, when receiving dental treatment and during pregnancy.

Investigations for cancer

This guideline for the first time recommends routine screening for cancer in patients over the age of 40 following an unprovoked VTE episode. This was based on a single study which showed no statistically significant reduction in cancer-related mortality, but the GDG felt that the non-significant reduction was potentially clinically and economically important, with patients and relatives also being reassured by negative investigations. Despite the lack of good evidence for a reduction in cancer-related mortality, the screening strategy used in the study showed an increased pick-up of cancers (in approximately 1 in 10 patients with 93% sensitivity) and at an earlier stage than in the standard care group. The study used a strategy of abdominal/pelvic CT or abdominal/pelvic ultrasound scan, alone or in combination with other tests (mammography, sputum cytology, tumour markers, faecal occult bloods and colonoscopy). The most cost-effective strategy, however, appeared to be abdominal/pelvic CT, mammography and sputum cytology on top of the routine screening using history/examination, chest radiograph, blood tests (including serum calcium and liver function) and urinalysis, all at the time of diagnosis. Sputum cytology was removed from the final recommendation due to its limited role in the diagnosis of lung cancer. The impact of additional radiation was not taken into consideration, since the increased risk of cancer was felt to be very small compared with the increased early detection of cancer.