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Venous Thromboembolism (VTE) Learning Zone
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VTE management

Declaration of sponsorship Pfizer and Bristol Myers Squibb
Read time: 80 mins
Last updated:27th Jul 2022
Published:25th Feb 2022

Management of venous thromboembolism (VTE) includes risk assessment, prevention, initial and primary treatment, and secondary prevention.

  • Learn about assessing the risk of thrombosis and bleeding in patients with VTE
  • Understand the latest recommendations for management of VTE, guidance for anticoagulation treatment, and how to determine which patients are suitable for outpatient treatment
  • Join Professor Stavros Konstantinides to explore guidance on key aspects of risk assessment and VTE management

VTE management guidelines

Clinical practice guidelines for management of VTE include:

  • 2019 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines1
  • 2020 American Society of Hematology (ASH) guidelines2
  • 2020 National Institute for Health and Care Excellence (NICE) guidelines3
  • 2021 European Society for Vascular Surgery (ESVS) guidelines4
  • 2021 update of the American College of Chest Physicians (CHEST) clinical practice guidelines5

The ASH, NICE and CHEST guidelines provide general recommendations for VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT)2,3,5; the ESC/ERS guidelines focus on PE1; and the ESVS guidelines focus on DVT and provide additional recommendations for another type of VTE, superficial vein thrombosis (SVT)4.

The guidelines emphasise the need for patient-centric care at different stages, including initial management, primary treatment and secondary prevention of VTE, and treatment of recurrent VTE1–4. They include recommendations on the type of treatment, dose and duration, and sequence of treatment for each stage1–5.

Guidelines now consider direct acting oral anticoagulants (DOACs) as the preferred option for oral treatment of intermediate-to-low risk PE (over vitamin K antagonists, VKAs), and for treatment of provoked or unprovoked proximal DVT (over VKAs or low molecular weight heparin followed by VKAs, respectively)1–4

The ESC/ERS, ASH and NICE guidelines provide conditional recommendations for primary treatment of uncomplicated DVT and low-risk PE at home1–3,5.

Recommendations are also provided for management of VTE based on patient features including pregnancy, the presence of cancer, renal impairment, cardiopulmonary disease and haemodynamic instability1,3.

In addition, thromboprophylaxis is recommended for patients with cancer who are hospitalised, as well as those who are ambulatory, receiving chemotherapy and are at intermediate- to high-risk of VTE 6–8.

For these patients who are at higher risk of VTE, anticoagulants recommended for thromboprophylaxis include DOACs, LMHW, fondaparinux and unfractionated heparin (UFH)6–8

An overview of VTE management

Management of VTE includes thromboprophylaxis for primary prevention of VTE in high-risk patients, and diagnostic assessment, treatment and follow-up of patients with VTE1,4,6–8.

Prevention of VTE in high-risk patients

VTE thromboprophylaxis is recommended for patients who are at higher risk of VTE, including patients with cancer who are hospitalised, receiving systemic chemotherapy, undergoing major cancer surgery, and ambulatory cancer patients at intermediate or high risk of VTE (Khorana score ≥2)6–8.

Learn about thromboprophylaxis in patients with cancer

Management of patients with VTE

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VTE risk assessment and prognostic stratification

For optimal management of venous thromboembolism (VTE), it is essential to understand a patient’s risk of thrombosis and risk of bleeding.

The balance between thrombotic and bleeding risk informs selection of treatment options for VTE and the duration of anticoagulation treatment. It also forms part of regular follow-up for patients on extended anticoagulation treatment, to determine whether continued anticoagulation treatment is still required1–4.

A patient’s risk of VTE recurrence and bleeding while on anticoagulants can be informed by clinical judgement, through evaluation of relevant risk factors, and/or using risk assessment tools1. For patients with pulmonary embolism (PE), prognostic risk stratification is an additional step that is recommended to guide management, including whether the patient may be considered for treatment at home.

Assessing risk of thrombosis

Generally, risk of thrombosis should be assessed:

  • To determine if patients are suitable for primary VTE prophylaxis (thromboprophylaxis)6–8. Thromboprophylaxis is recommended for patients at high risk of VTE, including patients with cancer who are hospitalised, receiving systemic chemotherapy, undergoing major cancer surgery, and ambulatory cancer patients at intermediate or high risk of VTE (Khorana score ≥2)6–8
  • In patients with VTE, to determine their risk of VTE recurrence2

Learn more about assessing risk of thrombosis in patients with cancer

How and when to assess risk of VTE recurrence?

After primary treatment of an initial VTE, the patient’s risk of VTE recurrence should be determined to inform the approach to management, including whether long-term anticoagulation will be required, and which treatment options are most appropriate2,3.

Identifying and characterising risk factors associated with the VTE

Guidelines recommend considering whether the initial VTE was associated with an identifiable risk factor (i.e. provoked VTE) or occurred in the absence of an identifiable/provoking risk factor (i.e. unprovoked)1,2,4.

If risk factors are identified, consider whether they are chronic (persistent) or transient (temporary), reversible, and whether they were present prior to the VTE event, as these can be associated with the rate of VTE recurrence and therefore influence duration of treatment1,2.

After discontinuing anticoagulation treatment, recurrence rates were 2.5% per year for PE associated with transient risk factors and 4.5% per year for PE that occurred in the absence of transient risk factors1

A summary of risk factors for VTE recurrence, classified according to risk of recurrence, is shown in Figure 2.

VTE_T2_Fig2.png

Figure 2. Risk factors for venous thromboembolism based on risk of recurrence over the long-term (Adapted1). PE, pulmonary embolism; VTE, venous thromboembolism. *If anticoagulation is discontinued after 3 months1.

An additional risk factor to consider is hereditary thrombophilia1. This may be suspected in patients aged <50 years who present with VTE in the absence of an otherwise identifiable risk factor, and especially if there is a strong family history of VTE1.

Risk prediction tools may assist decision-making

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Initial and primary VTE treatment

Treatment options for VTE include pharmacological anticoagulation treatments such as vitamin K antagonists (VKAs), low molecular weight heparin (LMWH), direct-acting oral anticoagulants (DOACs) and thrombolytic therapies.

Careful consideration of patient characteristics and comorbidities is essential, as management of VTE can be complicated by the presence of other conditions such as renal impairment, active cancer and antiphospholipid syndrome1–3. Management of VTE can also be influenced by use of concomitant medications, and patient characteristics such as age and extremes in body weight1–3.

In patients with cancer, challenges for VTE management include an elevated risk of recurrence and major bleeding, alongside cancer-associated treatments, procedures and related side effects6–8.

Learn about the challenges of managing VTE in patients with cancer

Interim anticoagulation while awaiting diagnosis

For patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE), interim anticoagulation should be commenced while awaiting results of diagnostic tests1,3, particularly for those with an intermediate or high probability of PE1.

Learn more about the diagnosis of PE

Options for interim anticoagulation include LMWH, fondaparinux or unfractionated heparin (UFH), DOACs or VKA (such as warfarin)1. It can be helpful to choose an interim anticoagulant that can be continued once diagnosis of DVT or PE is confirmed3. Usually, LMWH or fondaparinux are preferred over UFH (unless the patient has renal impairment or haemodynamic instability)1.

Initial and primary treatment of VTE

Following diagnosis of VTE, anticoagulation treatment should start at the initial treatment phase and be continued through the primary treatment phase, unless contraindicated2.

It is important to involve the patient in the decision-making process regarding short-term and long-term anticoagulation, and consider their preferences, to optimise and maintain treatment adherence1,3.

Considerations for initial management and choice of anticoagulant

Guidelines now consider DOACs as the preferred option for oral treatment of intermediate-to-low risk PE (over VKAs), and for treatment of provoked or unprovoked proximal DVT (over VKAs or LMWH followed by VKAs, respectively)1–4

An overview of the general approach to initial management of PE and proximal DVT is provided in Figure 4.

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Secondary prevention and recurrent VTE

Beyond the primary phase, venous thromboembolism (VTE) treatment may involve secondary prevention and treatment of recurrent VTE.

Secondary prevention

After completing primary treatment of VTE, a decision is required on whether to discontinue anticoagulation treatment or continue with long-term anticoagulation as secondary prevention of VTE recurrence2. In making this decision, healthcare professionals must weigh up the patient’s risk for recurrent VTE against their risk of bleeding1,2, involve the patient and take into account their preference and values3,5.

For pulmonary embolism (PE), extended anticoagulation may be indicated if the index event occurred in the presence of a minor transient or reversible risk factor, or a persisting risk factor2, or no identifiable risk factor1.

When considering extended anticoagulation for a patient with deep vein thrombosis (DVT), residual vein obstruction on ultrasound, and/or D-dimer level may assist in the decision-making process4.

Guideline suggestions and recommendations on when to discontinue or continue anticoagulation for secondary prevention are outlined in Table 2.

Table 2. Guideline suggestions for when anticoagulation may be discontinued after primary prevention or continued for secondary prevention1–3,5. DVT, deep vein thrombosis; IBD, inflammatory bowel disease; PE, pulmonary embolism; VKA, vitamin K antagonist; VTE, venous thromboembolism.

Consider discontinuing
anticoagulation
Consider continuing
anticoagulation
Treatment beyond the primary course is not typically required if:

· VTE is provoked by a major transient or temporary risk factor

· Provoking factor is no longer present and the clinical course has been uncomplicated










Long-term treatment may be considered for patients without a high risk of bleeding with:

· VTE associated with a persistent risk factor (such as IBD or autoimmune disorder)

· Unprovoked VTE (ie no major or minor transient risk factors); low dose apixaban or rivaroxaban may be preferred

· First episode of PE associated with no identifiable risk factor or minor transient or reversible risk factor

· Recurrent VTE not related to a major transient or reversible risk factor

· Antiphospholipid syndrome – consider oral anticoagulation treatment with VKA

Which anticoagulant to choose?

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References

  1. Konstantinides S v., Meyer G, Bueno H, Galié N, Gibbs JSR, Ageno W, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Heart Journal. 2020;41(4):543–603.
  2. Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism. Blood Advances. 2020;4(19):4693–4738.
  3. National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing: NICE Guideline. 2020.
  4. Kakkos SK, Gohel M, Baekgaard N, Bauersachs R, Bellmunt-Montoya S, Black SA, et al. European Society for Vascular Surgery (ESVS) 2021 clinical practice guidelines on the management of venous thrombosis. European Journal of Vascular and Endovascular Surgery. 2021;61(1):9–82.
  5. Stevens S, Woller S, Kreuziger L, Vintch J, Wells P, Moores L. Antithrombotic therapy for VTE disease, second update of the CHEST guideline and expert panel report. CHEST Journal (pulmonary vascular: guidelines and consensus statements). 2021;160(6):E545–E608.
  6. Key NS, Chb MB, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2019;38:496–520.
  7. National Comprehensive Cancer Network. NCCN Guidelines: Cancer-associated venous thromboembolic disease (version 3). 2021. Dated November 15, 2021.
  8. Lyman GH, Carrier M, Ay C, Nisio M di, Hicks LK, Khorana AA, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: Prevention and treatment in patients with cancer. Blood Advances. 2021;5(4):927–974.
  9. Badescu M, Ciocoiu M, Badulescu O, Vladeanu M-C, Bojan I, Vlad C, et al. Prediction of bleeding events using the VTE‑BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review). Experimental and Therapeutic Medicine. 2021;22(5).
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