Venous Thromboembolic Diseases: Management in Secondary Care and Thrombophilia Testing

Overview

This specialist Guidelines summary covers the management of venous thromboembolic diseases in adults, and is intended for use by cardiologists in a secondary care setting. It aims to support effective treatment for people who develop deep vein thrombosis (DVT) or pulmonary embolism (PE). This summary also covers testing for conditions that can make a DVT or PE more likely, such as thrombophilia and cancer.

The guideline does not cover pregnant women. For a summary of the recommendations relevant to primary care on diagnosis, initial management and lipid measurement, and referral for specialist review, see the separate primary care Guidelines summary. For the complete set of recommendations, please refer to the full guideline.

Anticoagulation Treatment for Suspected or Confirmed Deep Vein Thrombosis or Pulmonary Embolism

Visual Summary of the Recommendations on Anticoagulation Treatment for Deep Vein Thrombosis or Pulmonary Embolism

Algorithm 1: Suspected Deep Vein Thrombosis: Diagnosis and Initial Management 

Algorithm 2: Suspected Pulmonary Embolism: Diagnosis and Initial Management

• 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 and shared decision making. 

For recommendations on interim therapeutic anticoagulation for suspected DVT or PE, and anticoagulation treatment for confirmed DVT or PE, please see the separate primary care Guidelines summary. 

Anticoagulation Treatment for Deep Vein Thrombosis or Pulmonary Embolism in People at Extremes of Body Weight

• Consider anticoagulation treatment with regular monitoring of therapeutic levels for people with confirmed proximal DVT or PE who weigh less than 50 kg or more than 120 kg to ensure effective anticoagulation. 

Note the cautions and requirements for dose adjustment and monitoring in the medicine's summary of product characteristics, and follow locally agreed protocols or advice from a specialist or multidisciplinary team. 

Anticoagulation Treatment for Pulmonary Embolism with Haemodynamic Instability

• For people with confirmed PE and haemodynamic instability, offer continuous UFH infusion and consider thrombolytic therapy (see the section in the full guidance on Thrombolytic Therapy). 

Anticoagulation Treatment for Deep Vein Thrombosis or Pulmonary Embolism with Renal Impairment or Established Renal Failure

For recommendations on anticoagulation treatment for DVT or PE with renal impairment or established renal failure, please see the separate primary care Guidelines summary.

Anticoagulation Treatment for Deep Vein Thrombosis or Pulmonary Embolism with Active Cancer

In March 2020, most anticoagulants were off label for the treatment of DVT or PE in people with active cancer. See NICE's information on prescribing medicines.

• Offer people with active cancer and confirmed proximal DVT or PE anticoagulation treatment for 3 to 6 months. Review at 3 to 6 months according to clinical need. For recommendations on treatment after 3 to 6 months, see the section in the guideline on Long-Term Anticoagulation for Secondary Prevention
• When choosing anticoagulation treatment for people with active cancer and confirmed proximal DVT or PE, take into account the tumour site, interactions with other drugs, including those used to treat cancer, and the person's bleeding risk
• Consider a direct-acting oral anticoagulant (DOAC) for people with active cancer and confirmed proximal DVT or PE
• If a DOAC is unsuitable consider LMWH alone or LMWH 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
• For people with confirmed DVT or PE and cancer that is in remission, follow the recommendations in the section in the full guideline on Anticoagulation Treatment for Confirmed DVT or PE. 

Anticoagulation Treatment for Deep Vein Thrombosis or Pulmonary Embolism with Triple Positive Antiphospholipid Syndrome

• Offer people with confirmed proximal DVT or PE and an established diagnosis of triple positive antiphospholipid syndrome LMWH 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. 

For recommendations on treatment failure, please see the separate primary care Guidelines summary. 

NICE Technology Appraisal Guidance on Anticoagulation Treatment for Confirmed Deep Vein Thrombosis or Pulmonary Embolism 

• For NICE technology appraisal guidance see:
  • apixaban for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism
  • dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism
  • edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism
  • rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism
  • rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism.

Long-term Anticoagulation for Secondary Prevention

• Assess and discuss the benefits and risks of continuing, stopping or changing the anticoagulant with people who have had anticoagulation treatment for 3 months (3 to 6 months for people with active cancer) after a proximal DVT or PE. Follow the recommendations on shared decision making and supporting adherence in the NICE guidelines on medicines optimisation, medicines adherence and patient experience in adult NHS services.
• Consider stopping anticoagulation treatment 3 months (3 to 6 months for people with active cancer) after a provoked DVT or PE if the provoking factor is no longer present and the clinical course has been uncomplicated. If anticoagulation treatment is stopped, give advice about the risk of recurrence and provide:
  • written information on symptoms and signs to look out for
  • 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 
• Consider continuing anticoagulation beyond 3 months (6 months for people with active cancer) after an unprovoked DVT or PE. Base the decision on the balance between the person's risk of venous thromboembolism (VTE) recurrence and their risk of bleeding. Discuss the risks and benefits of long-term anticoagulation with the person, and take their preferences into account
• Explain to people with unprovoked DVT or PE and a low bleeding risk that the benefits of continuing anticoagulation treatment are likely to outweigh the risks
• Do not rely solely on predictive risk tools to assess the need for long-term anticoagulation treatment 
• Consider using the HAS–BLED score for major bleeding risk to assess the risk of major bleeding in people having anticoagulation treatment for unprovoked proximal DVT or PE. Discuss stopping anticoagulation if the HAS–BLED score is 4 or more and cannot be modified
• Take into account the person's preferences and their clinical situation when selecting an anticoagulant for long-term treatment
• For people who do not have renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg):
  • offer continued treatment with the current anticoagulant if it is well tolerated, or
  • if the current treatment is not well tolerated, or the clinical situation or person's preferences have changed, consider switching to apixaban if the current treatment is a direct-acting anticoagulant other than apixaban
• For people with renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg), consider carrying on with the current treatment if it is well tolerated
• If anticoagulation treatment fails follow the recommendations from the section in the full guideline on Treatment Failure
• For people who decline continued anticoagulation treatment, consider aspirin 75 mg or 150 mg daily. 

In March 2020, the use of aspirin for secondary prevention of DVT or PE was off label. See NICE's information on prescribing medicines. 

• Review general health, risk of VTE recurrence, bleeding risk and treatment preferences at least once a year for people taking long-term anticoagulation treatment or aspirin. 

For recommendations on information and support for people having anticoagulation treatment, see the separate primary care Guidelines summary.

Thrombolytic Therapy

Deep Vein Thrombosis

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

See NICE's interventional procedures guidance on ultrasound-enhanced, catheter-directed thrombolysis for deep vein thrombosis.

Pulmonary Embolism 

• Consider pharmacological systemic thrombolytic therapy for people with PE and haemodynamic instability (see also the section in the full guideline on Anticoagulation Treatment for PE With Haemodynamic Instability) 
• Do not offer pharmacological systemic thrombolytic therapy to people with PE and haemodynamic stability with or without right ventricular dysfunction (see also the section in the full guideline on Anticoagulation Treatment for DVT or PE). If the person develops haemodynamic instability, see the section in the full guideline on Anticoagulation Treatment for PE with Haemodynamic Instability. 

See NICE's interventional procedures guidance on ultrasound-enhanced, catheter-directed thrombolysis for pulmonary embolism.

Mechanical Interventions

Inferior Vena Caval Filters

• Do not offer an inferior vena caval (IVC) filter to people with proximal DVT or PE unless:
  • it is part of a prospective clinical study, or
  • anticoagulation is contraindicated or a PE has occurred during anticoagulation treatment (see the following two recommendations)
• Consider an IVC filter for people with proximal DVT or PE when anticoagulation treatment is contraindicated. Remove the IVC filter when anticoagulation treatment is no longer contraindicated and has been established 
• Consider an IVC filter for people with proximal DVT or PE who have a PE while taking anticoagulation treatment only after taking the steps outlined in the recommendation on treatment failure in the section in the full guidance on Anticoagulation Treatment for Suspected or Confirmed DVT or PE 
• Before fitting an IVC filter, ensure that there is a strategy in place for it to be removed at the earliest possible opportunity. Document the strategy and review it if the clinical situation changes. 

Elastic Graduated Compression Stockings

For recommendations for elastic graduated compression stockings, see the separate primary care Guidelines summary.

Percutaneous Mechanical Thrombectomy

See NICE's interventional procedures guidance on percutaneous mechanical thrombectomy for acute deep vein thrombosis of the leg.

Investigations for Cancer

• For people with unprovoked DVT or PE who are not known to have cancer, review the medical history and baseline blood test results including full blood count, renal and hepatic function, PT and APTT, and offer a physical examination
• Do not offer further investigations for cancer to people with unprovoked DVT or PE unless they have relevant clinical symptoms or signs (for further information, see the NICE guideline on suspected cancer). 

Thrombophilia Testing

• Do not offer testing for hereditary thrombophilia to people who are continuing anticoagulation treatment
• Do not offer thrombophilia testing to people who have had provoked DVT or PE
• Consider testing for antiphospholipid antibodies in people who have had unprovoked DVT or PE if it is planned to stop anticoagulation treatment, but be aware that these tests can be affected by anticoagulants and specialist advice may be needed
• Consider testing for hereditary thrombophilia in people who have had unprovoked DVT or PE and who have a first‑degree relative who has had DVT or PE if it is planned to stop anticoagulation treatment, but be aware that these tests can be affected by anticoagulants and specialist advice may be needed 
• Do not routinely offer thrombophilia testing to first‑degree relatives of people with a history of DVT or PE and thrombophilia.