Section 1: Introduction

For full diagnosis and treatment pathways for acute DVT, suspected and confirmed PE, please refer to Related Resources within SECTION 1: Introduction of the Antithrombotic guide.

Prior to commencing any antithrombotic therapy, all patients should have the following investigations:

• FBC
• U+Es
• Liver function test
• Calcium
• PT/INR and aPTT
• A pregnancy test should be performed for women of child-bearing potential

All patients should have a full history and examination. Patients with any concerning symptoms or signs should have targeted further investigations to investigate for an underlying cancer. Studies have demonstrated that routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit.

The following further investigations are recommended:

• Chest X-ray, if not performed in the past year
• Breast examination
• Ensure cervical smear up to date
• PSA in men over 40 years of age

Apixaban is the first-choice anticoagulant for treatment of VTE in NHS Borders, and is suitable for most people, including patients with malignancy. It has a lower bleeding risk than warfarin and other VKAs, and recent evidence indicates it has a lower bleeding risk than other DOACs at therapeutic doses. It is also more cost-effective and, for most patients, more tolerable than LMWH. In addition, in people with normal renal function and blood counts, routine monitoring is only required on an annual basis or when clinical circumstances demand. However, DOACs are not recommended in patients with proven or strong clinical suspicion of antiphospholipid syndrome.

Please see SECTION 5: DOACs for more information on cautions and contraindications of DOACs, use in extremes of weight and reversal.

For patients needing LMWH, please see SECTION 3: Venous thromboembolism: LMWH.

For patients needing warfarin, please see SECTION 6: Vitamin K antagonists.

The duration of anticoagulation depends on an individual's risk of recurrent thrombosis off anticoagulation versus the risk of major bleeding on anticoagulation. It is important to take into consideration that the consequences of a major bleed are generally more severe than the consequences of a recurrent episode of venous thromboembolism (VTE) (e.g. case-fatality rate of ~10% versus ~5%, respectively). The patient's preference, quality of life and other functional issues also need to be considered.

Recurrent episodes of VTE may be due to extension of the original thrombus or may be due to a new episode of VTE that is unrelated to the initial episode. The risk of recurrence reflects the patient's underlying predisposition to VTE and persists as long as an acquired risk factor is present (e.g. patients with cancer) or indefinitely (e.g. patients with unprovoked VTE).

The risk of bleeding differs among patients, with the highest risk in older patients and during the first month of anticoagulation. Anticoagulant therapy should be stopped when the benefits no longer clearly outweigh the risks, or when patients who are fully informed and have a good understanding of the associated risks want to stop, even if continuation of treatment is expected to be of overall benefit.

The minimum duration of treatment of VTE is considered to be 3 months, as a shorter duration is associated with a significant increase in recurrence risk. After acute treatment of VTE, if the risk of recurrence outweighs the risk of bleeding, anticoagulation may be continued for secondary prevention of VTE.

In patients with a first unprovoked VTE, the decision to stop anticoagulant therapy at 3 months or to continue treatment indefinitely is strongly influenced by the preferences of an informed patient. To enable shared decision making, the expected risks of recurrence with and without indefinite anticoagulant therapy, and the expected consequences of recurrent VTE and bleeding, need to be explained to the patient.

VTE provoked by a transient risk factor

Patients with VTE provoked by a transient risk factor- see table 1, have a much lower risk of recurrence than those with an unprovoked VTE or a persistent risk factor.

Table 1. Transient risk factors that can provoke a VTE

The stronger the provoking risk factor is (e.g. recent major surgery), the lower the expected risk of recurrence after stopping anticoagulant therapy. Note that temporary immobility risk factors (e.g. confined to bed ≥3 days or a flight of <6 hours) are weak risk factors.

In the first year after stopping therapy for VTE with a transient risk factor, the risk of recurrence is about 1-2% if VTE was provoked by a major risk factor and about 5% if VTE was provoked by a minor risk factor. By 5 years, the risk of recurrence is approximately 3-fold higher (3% for major risk factor, 15% for minor risk factor).

Cancer-associated VTE

Risk of recurrent VTE is markedly increased in patients with active cancer (20% per patient-year); the risk is higher in patients with metastatic compared with localised disease. The risk of recurrent VTE may be lower if it occurred during chemotherapy and the chemotherapy has been stopped.

People who experience a cancer-associated VTE and are subsequently cured of cancer generally have a low risk of recurrent VTE.

Unprovoked VTE

Patients with a first unprovoked episode of DVT or PE on average have a risk of recurrence of about 10% in the first year, 30% in the first 5 years and 50% in the first 10 years after stopping anticoagulant therapy.

Several methods to further stratify the recurrence risk have been proposed. As a result of their poor performance in validation cohorts, risk scores, such as DASH and HERDOO-2, are not recommended for routine use in guiding duration of anticoagulation.

The following may be taken into account in decision-making:

• The recurrence risk in men is approximately 1.5-fold higher than that in women.
  
  
• The recurrence risk in people with an elevated D-dimer level at one month after cessation of anticoagulation for proximal DVT or PE is approximately twice that of people with a normal D-dimer level.
  
  
• People whose index VTE event was a PE are 3 to 4 times more likely to experience a PE as their recurrent event than people whose index event was a DVT.
  
  
• The presence of residual abnormalities on ultrasound is detected in approximately one third of patients and does not appear to be a clinically-important risk factor for recurrence after stopping anticoagulant therapy.
  
  
• People with isolated calf (distal) DVT have a 50% lower risk of recurrence than those with proximal DVT or PE.
  
  
• People with a second episode of VTE have a higher risk of recurrence.
  
  
• With the exception of appropriate testing for antiphospholipid syndrome, thrombophilia testing only has a very limited role in guiding decisions about duration of anticoagulation

Risk of bleeding with anticoagulation

The risk of bleeding secondary to anticoagulation is highest during the first 3 months of treatment and stabilises after the first year.

Risk of bleeding differs markedly among patients depending on the prevalence of risk factors (e.g. age>75yrs; previous bleeding; cancer (including metastatic); renal failure; liver failure; thrombocytopenia; previous stroke; diabetes; anaemia; antiplatelet therapy; poor anticoagulant control; recent surgery; frequent falls; alcohol abuse).

Patients without any risk factors have a low annual risk of major bleeding at 0.8% while those with two or more risk factors have an annual risk greater than 6%. There are no well-validated scoring systems for predicting bleeding risk when anticoagulated for previous VTE.

Recommendations

• Patients with their first VTE provoked by any transient risk factor(s) should receive a minimum of 3 months of anticoagulant therapy.
  
  
• Although 3 months is the usual length of time-limited treatment, 6 months may be preferred if:
  
  • (i) the VTE was very large or very symptomatic
  • (ii) the symptoms of the initial VTE persist
  • (iii) the patient is not ready (confident) to stop anticoagulant therapy at 3 months
  • (iv) the patient does not have a high risk for bleeding
    
    
• Patients with their first unprovoked episode of VTE should receive a minimum of 3 months anticoagulant therapy and then be assessed for indefinite anticoagulant therapy. If patients have a high bleeding risk, anticoagulation should be stopped. All other patients should be considered for indefinite treatment.
  
  
• For the majority of patients with an isolated calf (distal) DVT treated with anticoagulation, treatment duration should be 3 months. A longer course may be necessary if:
  • (i) symptoms persist
  • (ii) the patient is not ready (confident) to stop anticoagulant therapy
  • (iii) the patient does not have a high risk for bleeding. In particular, men under the age of 50 with an unprovoked distal DVT appear to have a higher recurrence risk and should be considered for indefinite anticoagulation
    
    
• Patients with a central venous catheter (CVC) -associated VTE should receive 3 months of anticoagulation and longer if the patient continues to have a CVC.
  
  
• For patients with a second episode of VTE, if both episodes were provoked by a transient risk factor which has since resolved, treat for 3 months, followed by prophylaxis if there are any other risk factors.
  
  
• A second episode of unprovoked VTE is a strong indication for indefinite anticoagulant therapy unless there is a very high bleeding risk.
  
  
• Patients with active cancer and VTE should receive indefinite anticoagulant therapy. Cancer patients with potentially curable disease and VTE should be treated for a minimum of 3 months but should continue if they are undergoing systemic anti-cancer therapy (SACT) until this is completed.
  
  
• Patients who have been recommended indefinite anticoagulant therapy should be reassessed periodically (e.g. annually) to re-estimate the VTE vs bleeding risk balance. Follow up in primary care may be suitable in this context.

Table 2. Summary of recommendations

Please refer to the thrombophilia guidance in Related Resources for advice on inherited, APS and other thrombophilias.

The information below provides guidance on management of other VTEs.

Thrombolysis

For management of massive pulmonary embolism and systemic thrombolysis, please refer to Related Resources.

For catheter-directed thrombolysis for phlegmasia caerulea dolens or limb-threatening DVT, patients should be discussed with on-call vascular surgeon (via NHS Lothian switchboard - 0131 537 1000) to access this service.

Incidental asymptomatic VTE

In patients who are unexpectedly found to have asymptomatic DVT or PE, the same initial and long-term anticoagulation is recommended as for comparable patients with symptomatic VTE.

Upper limb DVT

All suspected cases should have an ultrasound examination; pre-test probability assessment and D-dimers are not used. Initial treatment is the same as for lower limb DVT; recurrence rates for upper limb DVT after treatment for 3-6 months are low and it is likely that prolonged anticoagulation is not required for most patients. Further investigation is required to exclude thoracic outlet obstruction and individual cases should be discussed with radiology regarding further imaging.

Superficial thrombophlebitis (STP)

For management of STP, please refer to Related Resources.

If the STP is <3cm of the sapheno-femoral junction (SFJ), or deep perforators at the popliteal region, this should be treated as a DVT. Where the STP is ≥ 3 cm from the SFJ or deep perforators at the popliteal region and extending ≥ 5 cm in length, evidence is unclear. Management should be consultant-directed until local guidance has been finalised - link will be added to Related Resources within SECTION 1: Introduction of the Antithrombotic guide.

Thrombosis at unusual sites

For management of cerebral vein sinus thrombosis (CVST), please refer to the CVST pathway in Related Resources.

Splenic / mesenteric / portal vein thrombosis – if this has been provoked by intra-abdominal sepsis, surgery, etc., a finite period of anticoagulation is advised, commonly 6 months. Follow up imaging is recommended to evaluate the extent of recanalisation. Thrombophilia testing is NOT needed. For portal vein thrombosis in the context of (pre-existing) cirrhosis, liaison with gastroenterology is needed regarding risk of variceal bleeding and duration of anticoagulation.

For unprovoked thrombosis, refer to thrombophilia testing guidance in Related Resources within SECTION 1: Introduction prior to decisions about choice of anticoagulation. Refer to haematology clinic for follow up. And in the context of unprovoked portal vein thrombosis, refer to gastroenterology.