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Venous thromboembolic diseases: Pulmonary embolism

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1 Venous thromboembolic diseases: Pulmonary embolism
This slide set was updated in October 2013 and includes details of the NICE quality standard for management of venous thromboembolic diseases. The NICE clinical guideline has not changed ABOUT THIS PRESENTATION: This educational slide set has been developed to support education and learning about the NICE clinical guideline on VTE diseases. It focuses on the recommendations for pulmonary embolism and is a component of the workshop set out in the NICE education and learning pulmonary embolism training plan (http://guidance.nice.org.uk/CG144/EducationResource/PETrainingPlan/doc/English). This guideline has been written for healthcare professionals caring for adults with VTE diseases in primary, secondary and tertiary care settings. The guideline is available in a range of formats (from including a NICE Pathway. You may want to print copies of the guideline for your training session, for the audience to refer to. You can add your own organisation’s logo alongside the NICE logo. DISCLAIMER This educational slide set is an implementation tool and should be used alongside the published guidance. This information does not supersede or replace the guidance itself. PROMOTING EQUALITY Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties. Support for education and learning slide set 2013 NICE clinical guideline 144

2 What this presentation covers
Background Scope Recommendations Discussion NICE quality standard NICE Evidence Services NICE Pathway Find out more NOTES FOR PRESENTERS: In this presentation we will start by providing some background to the guideline and why it is important. We will then present details of the PE related recommendations with information and rationale to support the recommendations. Then we will open the meeting up with a list of questions to help prompt a discussion on local issues for incorporating the guidance into practice. Links to the NICE quality standard, NICE Evidence Services and the NICE Pathway are provided. Finally, we will end the presentation with further information about the support provided by NICE.

3 Glossary INR: International normalised ratio
VTE: Venous thromboembolism PE: Pulmonary embolism DVT: Deep vein thrombosis CTPA: CT pulmonary angiogram V/Q SPECT: Ventilation perfusion scan PTS: Post-thrombotic syndrome VKA: Vitamin K antagonist UFH: Unfractionated heparin LMWH: Low molecular weight heparin NOTES FOR PRESENTERS: International normalised ratio (INR) A standardised laboratory measure of blood coagulation used to monitor the adequacy of anticoagulation in patients who are having treatment with a vitamin K antagonist. V/Q SPECT Ventilation perfusion scan (single photon emission computerised tomography) Post-thrombotic syndrome (PTS) A chronic condition characterised by symptoms and signs that develop after DVT as a result of damage to the deep veins and their valves. Vitamin K antagonist (VKA) Warfarin is an example of this.

4 Definitions Provoked DVT or PE: DVT or PE in patients with recent occurrence of major clinical risk factor for VTE Proximal DVT: DVT in popliteal vein or above Renal impairment: eGFR of less than 90 ml/minute/1.73 m2 (see notes) Unprovoked DVT or PE: DVT or PE in patients with no recently occurring major clinical risk factors for VTE or patients with active cancer, thrombophilia or family history of DVT (these are risks, but they are constant) Wells score: clinical prediction rules for estimating probability of DVT and PE NOTES FOR PRESENTERS: The following terms are used in this guideline. Provoked deep vein thrombosis (DVT) or pulmonary embolism (PE) 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). Proximal DVT DVT in the popliteal vein or above. Proximal DVT is sometimes referred to as ‘above-knee DVT’. Renal impairment Reduced renal function that may be acute or chronic. An estimated glomerular filtration rate of less than 90 ml/minute/1.73 m2 indicates a degree of renal impairment in chronic kidney disease. (For NICE guidance on the classification of chronic kidney disease see ‘Chronic kidney disease’ [NICE clinical guideline 73]). Unprovoked DVT or PE DVT or PE in a patient with: no antecedent major clinical risk factor for VTE (see ‘Provoked deep vein thrombosis or pulmonary embolism’ above) who is not having hormonal therapy (oral contraceptive or hormone replacement therapy) or active cancer, thrombophilia or a family history of VTE, because these are underlying risks that remain constant in the patient. Wells scores Clinical prediction rules for estimating the probability of DVT and PE. There are a number of versions of Wells scores available. This guideline recommends the two-level DVT Wells score and the two-level PE Wells score.

5 Background Thrombus (blood clot) forms in a vein
Deep vein thrombosis - in deep veins of leg or pelvis Pulmonary embolism - thrombus dislodges and travels to pulmonary arteries Term ‘venous thromboembolism’ includes DVT and PE Risk factors include: thrombophilia, history of DVT, surgery, obesity, acute illness, cancer and immobility 500,000 people in Europe die from preventable hospital-acquired VTE every year NOTES FOR PRESENTERS: Key points to raise: Venous thromboembolism (VTE) is a condition in which a blood clot (a thrombus) forms in a vein, most commonly in the deep veins of the legs or pelvis. This is known as deep vein thrombosis, or DVT. The thrombus can dislodge and travel in the blood, particularly to the pulmonary arteries. This is known as pulmonary embolism, or PE. The term ‘VTE’ includes both DVT and PE. Venous thromboembolic diseases cover a spectrum ranging from asymptomatic calf vein thrombosis to symptomatic DVT. They can be fatal if they lead to PE, in which the blood supply to the lungs is badly blocked by the thrombus. Non-fatal VTE can cause serious long-term conditions such as post-thrombotic syndrome. Thrombophilia is a major risk factor for VTE. It is an inherited or acquired prothrombotic state that predisposes to venous thromboembolism. Other major risk factors for VTE include a history of DVT, age over 60 years, surgery, obesity, prolonged travel, acute medical illness, cancer, immobility and pregnancy. Failure to diagnose and treat VTE correctly can result in fatal PE. However, diagnosis of VTE is not always straightforward. It has been estimated that every year preventable hospital-acquired VTE causes more than 500,000 deaths in Europe (Cohen et al. 2007). References Cohen AT, Agnelli G, Anderson FA et al. (2007) Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thrombosis & Haemostasis 98:

6 Scope Guidance on management of VTE, investigations for cancer in patients with VTE and thrombophilia testing Covers adults with suspected or confirmed DVT or PE Includes advice on the Wells score, D-dimer measurement, ultrasound and radiological imaging Does not cover those younger than 18, or women who are pregnant NOTES FOR PRESENTERS. Key points to raise: The Venous thromboembolic diseases clinical guideline includes advice on the Wells score, D-dimer measurement, ultrasound and radiological imaging. It also offers guidance on the management of VTE, investigations for cancer in patients with VTE and thrombophilia testing. The guideline covers adults with suspected or confirmed DVT or PE. It does not cover children or young people aged under 18, or women who are pregnant. Additional information To ensure comprehensive management and continuity when developing a programme of care for patients who are at risk of or who develop VTE, users of this guideline are encouraged to refer to NICE guidance on Venous thromboembolism: reducing the risk (NICE clinical guideline 92), Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults (NICE technology appraisal guidance 170), Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults (NICE technology appraisal guidance 157) and Medicines adherence (NICE clinical guideline 76) (see also section 6 of the NICE clinical guideline 144). The guideline will assume that prescribers will use a drug’s summary of product characteristics to inform decisions made with individual patients. This guideline recommends some drugs for indications for which they do not have a UK marketing authorisation at the date of publication, if there is good evidence to support that use. Where recommendations have been made for the use of drugs outside their licensed indications (‘off-label use’), these drugs are marked with a footnote in the recommendations.

7 Recommendations for PE
Diagnostic investigations and diagnosis Treatments pharmacological interventions thrombolytic therapy mechanical interventions Patient information verbal and written self-management Investigations for cancer Thrombophilia testing NOTES FOR PRESENTERS: The NICE guideline contains 38 recommendations, of which 28 are related to the diagnosis, treatment and management of PE. The PE related recommendation are divided into the following sections: Diagnostic investigations and diagnosis Treatments (pharmacological interventions, thrombolytic therapy, and mechanical interventions) Patient information: verbal and written self-management Investigations for cancer Thrombophilia testing

8 Diagnostic investigations (1)
In patients presenting with signs or symptoms of PE, carry out the following to exclude other causes: an assessment of their general medical history a physical examination and a chest X-ray If PE suspected use the two-level PE Wells score NOTES FOR PRESENTERS: Recommendations in full If a patient presents with signs or symptoms of PE, carry out an assessment of their general medical history, a physical examination and a chest X-ray to exclude other causes. [1.1.7] If PE is suspected, use the two-level PE Wells score (use hyperlink on slide or see table 2 in the NICE clinical guideline) to estimate the clinical probability of PE. [1.1.8] Related recommendations If a patient presents with signs or symptoms of both DVT (for example a swollen and/or painful leg) and PE (for example chest pain, shortness of breath or haemoptysis), carry out initial diagnostic investigations for either DVT or PE, basing the choice of diagnostic investigations on clinical judgement. [1.1.14] Additional information: Effective diagnosis is crucial because PE is a treatable condition and severe cases of PE can lead to collapse and/or sudden death. Some PEs are rapidly fatal, and in the majority of the fatal cases they are not clinically diagnosed before death. The symptoms and signs of PE are not specific and include dyspnoea, pleuritic chest pain (due to pleural irritation in pulmonary infarction), retrosternal chest pain (due to right ventricular ischaemia), cough and haemoptysis. In severe cases the right ventricle fails, leading to dizziness and/or syncope. Assessing the general medical history and physical examination does not present any harm to the patient and may pick up or exclude other possible causes for the patient’s symptoms. Completing this step of the diagnosis is crucial, as it will direct the consecutive diagnostic pathway to be undertaken for the patient. Using a clinical prediction rule is the first step in the diagnosis of PE, by categorising patients presenting with suspected PE into different pre-test probabilities. Establishing groups with different pre-tests risks helps determine which tests would be appropriate for the purpose of ruling out PE or confirming it. Due to the weight of one subjective item in the two-level PE Wells score (“alternative diagnosis less likely than PE” – 3 points allocated), the experience and expertise of the person doing the scoring is an important consideration which could determine the effectiveness of the pre-test probability scoring system.

9 Diagnostic investigations (2)
Two-level PE Wells score PE likely PE unlikely 1. Offer immediate CTPA 1. Offer a D-dimer test 2. If CTPA not immediately available offer interim parenteral anticoagulant therapy followed by CTPA 2. If D-dimer positive offer immediate CTPA 3. If CTPA negative and DVT suspected consider proximal leg vein ultrasound 3. If CTPA not immediately available offer interim parenteral anticoagulant therapy followed by CTPA NOTES FOR PRESENTERS: Recommendations in full Offer patients in whom PE is suspected and with a likely two-level PE Wells score either: an immediate computed tomography pulmonary angiogram (CTPA) or immediate interim parenteral anticoagulant therapy followed by a CTPA, if a CTPA cannot be carried out immediately. Consider a proximal leg vein ultrasound scan if the CTPA is negative and DVT is suspected. [KPI 1.1.9] Offer patients in whom PE is suspected and with an unlikely two-level PE Wells score a D-dimer test and if the result is positive offer either: an immediate CTPA or immediate interim parenteral anticoagulant therapy followed by a CTPA, if a CTPA cannot be carried out immediately. [KPI ] For patients who have an allergy to contrast media, or who have renal impairment, or whose risk from irradiation is high: Assess the suitability of a ventilation/perfusion single photon emission computed tomography (V/Q SPECT) scan or, if a V/Q SPECT scan is not available, a V/Q planar scan, as an alternative to CTPA. If offering a V/Q SPECT or planar scan that will not be available immediately, offer interim parenteral anticoagulant therapy. [1.1.11] Additional information For ruling out PE, the GDG (Guideline Development Group) identified that in the group with PE “unlikely” when using a combination of clinical prediction scores such as a PE Wells score and D-dimer test, the number of PE cases missed was very low. CTPA is a sensitive test and people with PE are unlikely to be missed. It also allows the observation of right heart dysfunction and detection of other abnormalities in the chest. V/Q scan is a possible alternative to CTPA in patients with concerns about the level of radiation and adverse effects from contrast media (e.g. renal impairment and contrast media allergy) but does not provide all the benefits of CTPA. Because PE is potentially life threatening, the GDG agreed that if immediate CTPA is not available the potential harms from a dose of a parenteral anticoagulant is less than the potential harms from delay of treatment.

10 Diagnosis Diagnose PE and start treatment if positive CTPA or if PE identified with V/Q SPECT or planar scan Consider alternative diagnoses in patient with: unlikely two-level PE Wells score and: negative D-dimer test or positive D-dimer test and negative CTPA likely two-level PE Wells score and: negative CTPA and no suspected DVT NOTES FOR PRESENTERS: Recommendations in full Diagnose PE and treat (see section 1.2 of the NICE clinical guideline [slides of this slide set]) patients with a positive CTPA or in whom PE is identified with a V/Q SPECT or planar scan. [1.1.12] Take into consideration alternative diagnoses in the following two groups of patients: Patients with an unlikely two-level PE Wells score and either: - a negative D-dimer test or - a positive D-dimer test and a negative CTPA. Patients with a likely two-level PE Wells score and both: - a negative CTPA and - no suspected DVT. Advise these patients that it is not likely they have PE and discuss with them the signs and symptoms of PE, and when and where to seek further medical help. [1.1.13] Additional information Based on the specificity of CTPA and V/Q, these tests are suitable for the purpose of confirming the presence of PE. The results of these tests are reliable after the patients have gone through the whole diagnostic pathway, which includes two-level Wells score and in some cases D-dimer. There is a high risk of PE in patients with positive CTPA or V/Q (see recommendation ). It will be beneficial and reassuring for patients to know that they are very unlikely to have a PE. However, they should be fully informed of signs and symptoms and when to seek help if new signs and symptoms appear or recur. The presence of signs and symptoms that suggest a possible DVT should be considered and investigated before PE is ruled out and patients are sent home (see recommendation ).

11 Pharmacological interventions (1)
Confirmed PE or proximal DVT Offer low molecular weight heparin (LMWH) or fondaparinux as soon as possible, unless: severe renal impairment increased risk of bleeding haemodynamically unstable Confirmed PE or proximal DVT and active cancer Offer LMWH, continue for 6 months NOTES FOR PRESENTERS: Recommendations in full Offer a choice of low molecular weight heparin (LMWH) or fondaparinux to patients with confirmed proximal DVT or PE, taking into account comorbidities, contraindications and drug costs, with the following exceptions: For patients with severe renal impairment or established renal failure (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73 m2) offer unfractionated heparin (UFH) with dose adjustments based on the APTT (activated partial thromboplastin time) or LMWH with dose adjustments based on an anti-Xa assay. For patients with an increased risk of bleeding consider UFH. For patients with PE and haemodynamic instability, offer UFH and consider thrombolytic therapy (see recommendations and on slide 13 or in the NICE clinical guideline). Start the LMWH, fondaparinux or UFH as soon as possible and continue it for at least 5 days or until the international normalised ratio (INR) (adjusted by a vitamin K antagonist [VKA]; see recommendation on slide 12 or in the NICE clinical guideline) is 2 or above for at least 24 hours, whichever is longer. [KPI 1.2.1] Offer LMWH to patients with active cancer and confirmed proximal DVT or PE, and continue the LMWH for 6 months1. At 6 months, assess the risks and benefits of continuing anticoagulation2. [KPI 1.2.2] Footnotes to recommendation 1.2.2 1: At the time of publication (June 2012) some types of low molecular weight heparin (LMWH) do not have a UK marketing authorisation for 6 months of treatment of DVT or PE in patients with cancer. Prescribers should consult the summary of product characteristics for the individual LMWH and make appropriate adjustments for renal impairment. Informed consent for off-label use should be obtained and documented. 2: Although this use is common in UK clinical practice, at the time of publication (June 2012) none of the anticoagulants has a UK marketing authorisation for the treatment of DVT or PE beyond 6 months in patients with cancer. Informed consent for off-label use should be obtained and documented. Additional information It is important that parenteral anticoagulation is achieved quickly for patients with VTE in order to reduce the risk of clot propagation or further embolic events. The economic evidence shows that LMWH is more cost-effective or cost-saving compared to UFH as a short-term treatment for PE or DVT. Advantages of LMWH and fondaparinux such as IM and no need for APTT monitoring over UFH mean that patients on LMWH and fondaparinux have a shorted hospital stay than those receive UFH Consider individual circumstances in order to offer most suitable agent for example; renal status; risk of bleeding or need for surgery or thrombolysis, risk of heparin induced thrombocytopaenia, appropriate dose and patient preference. In patients with cancer, the evidence suggests that anticoagulation for 6 months with LMWH leads to better outcomes compared to switching to a VKA after initial LMWH treatment. At 6 months, the need to continue anticoagulation should be reassessed and discussed with the patient. The current recommendation of international guidelines and UK clinical practice is to continue anticoagulation lifelong in patients with active cancer.

12 Pharmacological interventions (2)
Patients with confirmed PE or proximal DVT Offer a VKA to patients with confirmed proximal DVT or PE within 24 hours of diagnosis and continue the VKA for at least 3 months NOTES FOR PRESENTERS: Recommendations in full Offer a VKA to patients with confirmed proximal DVT or PE within 24 hours of diagnosis and continue the VKA for 3 months. At 3 months, assess the risks and benefits of continuing VKA treatment (see recommendations and below). [1.2.3] Related recommendations Offer a VKA beyond 3 months to patients with an unprovoked PE, taking into account the patient’s risk of VTE recurrence and whether they are at increased risk of bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment. [KPI 1.2.4] Consider extending the VKA beyond 3 months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their VKA treatment. [KPI 1.2.5] Additional information rivaroxaban NICE Technology Appraisal 261 (July 2012) ‘Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism’ is available at Additional information: VKA Oral VKAs may take a few days to reach a level that is effective for anticoagulation, which is why the initial parenteral anticoagulation should be continued as in recommendation This will ensure adequate anticoagulation at all times. VKA potentially improves VTE-related mortality in patients (without cancer) compared with LMWH. The additional benefits of extending treatment beyond 3 months are less clear and need to be considered for each patient based on their risk of recurrences and bleeding. Patients who do not adhere to follow up visits and INR monitoring may be at higher risk of poor anticoagulation control, bleeding and VTE recurrences. This needs to be assessed when deciding treatment choices. VKA use also needs to be considered in groups prone to falls, such as the elderly, as they will be at an increased risk of bleeds. In patients where VKA cannot be adequately monitored, alternative treatments may be required.

13 Thrombolytic therapy For patients with PE and haemodynamic instability consider thrombolytic therapy Do not offer to patients with PE and haemodynamic stability NOTES FOR PRESENTERS: Recommendations in full Consider pharmacological systemic thrombolytic therapy for patients with PE and haemodynamic instability (see also recommendation on slide 11 or in the NICE clinical guideline). Related recommendation Do not offer pharmacological systemic thrombolytic therapy to patients with PE and haemodynamic stability (see also recommendation on slide 11 or in the NICE clinical guideline). [1.2.8] Additional information: Thrombolytic therapy promotes lysis of blood clots. The risk of mortality from PE compared with the risk of bleeding are the most important factors in deciding whether to offer thrombolytic therapy. In haemodynamically unstable patients there is a higher risk of mortality, and the evidence showed that the benefit from the reduction of mortality outweighs the risk of bleeding in this group. However, there is likely to be heterogeneity in the group and treatment should be considered on a patient-to- patient basis. There is overall harm if the treatment is given to patients with lower risk of death but higher risk of bleeding.

14 Mechanical interventions
Temporary inferior vena caval filters: offer to patients with proximal DVT or PE who cannot have anticoagulation treatment consider for patients with recurrent proximal DVT or PE despite adequate anticoagulation treatment (after considering alternatives) Ensure strategy for removing filter at earliest possible opportunity is planned and documented when filter is placed NOTES FOR PRESENTERS: Recommendations in full Offer temporary inferior vena caval filters to patients with proximal DVT or PE who cannot have anticoagulation treatment, and remove the inferior vena caval filter when the patient becomes eligible for anticoagulation treatment. [1.2.10] Consider inferior vena caval filters for patients with recurrent proximal DVT or PE despite adequate anticoagulation treatment only after considering alternative treatments such as: increasing target INR to 3–4 for long-term high-intensity oral anticoagulant therapy or switching treatment to LMWH. [1.2.11] Ensure that a strategy for removing the inferior vena caval filter at the earliest possible opportunity is planned and documented when the filter is placed, and that the strategy is reviewed regularly. [1.2.12] Additional information Inferior vena caval filters are designed to trap fragmented thromboemboli from the deep leg veins en route to the pulmonary circulation (while preserving blood flow in the IVC filter). Vena caval filters are usually placed under radiological guidance, approached from either the jugular or femoral vein. The risk of mortality from PE was considered to be high when left untreated. Some patients may not be able to tolerate anticoagulation because of excessive bleeding. The GDG identified circumstances where IVC filter maybe considered; patients who have had recent upper GI bleed or stroke (where use of anticoagulation significantly increases the risk of a repeat bleed), those needing surgery (high bleeding risk) those prone to falls or injury or those unwilling to attend anticoagulation clinics to have regulation of anticoagulation. Some people may have recurrent VTE despite adequate anticoagulation. For some patient insertion of a filter may influence the patient’s quality of life because it may be preferable to lifelong injections (although this must be balanced against higher risk of DVT or PE). Many filters are left in situ and forgotten. At the time of insertion of IVC filters there should be a clear management plan, including the indication for insertion, the intended length of time that the filter is likely to be necessary and the intended point at which the filter should be removed. As circumstances change, this management plan should be reviewed.

15 Patient information: verbal and written
How to use anticoagulants Duration of treatment Possible side effects and what to do Effects of other drugs, foods and alcohol Monitoring How anticoagulants may affect dental treatment Taking anticoagulants if they are planning pregnancy or become pregnant How activities may be affected When and how to seek medical help NOTES FOR PRESENTERS: Recommendation in full Give patients having anticoagulation treatment verbal and written information about: how to use anticoagulants duration of anticoagulation treatment possible side effects of anticoagulant treatment and what to do if these occur the effects of other medications, foods and alcohol on oral anticoagulation treatment monitoring their anticoagulant treatment how anticoagulants may affect their dental treatment taking anticoagulants if they are planning pregnancy or become pregnant how anticoagulants may affect activities such as sports and travel when and how to seek medical help. [1.3.1]

16 Patient information: self-management
Information and advice Anticoagulant information booklet Anticoagulant alert card Heparins of animal origin may be of concern to some patients Self monitoring of INR Do not routinely offer to PE or DVT patients NOTES FOR PRESENTERS: Recommendations in full Provide patients who are having anticoagulation treatment with an ‘anticoagulant information booklet’ and an ‘anticoagulant alert card’ and advise them to carry the ‘anticoagulant alert card’ at all times. [1.3.2] Be aware that heparins are of animal origin and this may be of concern to some patients. (see Religion or belief: a practical guide for the NHS). For patients who have concerns about using animal products, consider offering synthetic alternatives based on clinical judgement after discussing their suitability, advantages and disadvantages with the patient. [This recommendation is from Venous thromboembolism: reducing the risk (NICE clinical guideline 92).] [1.3.3] Do not routinely offer self-management or self-monitoring of INR to patients who have had DVT or PE and are having treatment with a VKA. [1.4.1] Additional information Educating patients about their condition could increase patient knowledge and awareness and lead to improved patient outcomes. To improve the adherence with carrying the card it is important to explain to patients the rationale and the benefit of carrying it. Source of information already available: National Patient Safety Agency. Oral anticoagulant therapy: important information for patients Available from: Note - On 1 June 2012 the key functions and expertise for patient safety developed by the National Patient Safety Agency (NPSA) transferred to the NHS Commissioning Board Special Health Authority. The hyperlink and information provided continued to be valid at the time of publication.

17 Investigations for cancer (1)
Offer all patients with unprovoked DVT or PE, who are not known to have cancer : physical examination (guided by patient’s full history) and chest X-ray and blood tests (full blood count, serum calcium and liver function tests) and urinalysis NOTES FOR PRESENTERS: Recommendation in full Offer all patients diagnosed with unprovoked DVT or PE who are not already known to have cancer the following investigations for cancer: a physical examination (guided by the patient’s full history) and a chest X-ray and blood tests (full blood count, serum calcium and liver function tests) and urinalysis. [1.5.1] Additional information During the process of malignant transformation, tumours produce several proteins, such as tissue factor, which enable the tumour cells to invade and metastasise. Tissue factor simultaneously activates the coagulation cascade leading to VTE. The clearest benefit of the recommended cancer screening is in the change in pharmacological management and duration of anticoagulation for VTE, in those whose underlying cancer is diagnosed, leading to a significant reduction in VTE recurrence rates. Early diagnosis of underlying cancer may lead to diagnosis at an earlier, curative stage and improvement in cancer-related mortality. Physical examination, medical history documentation and baseline tests should be conducted and interpreted with a focus on the possibility that a patient with unprovoked VTE (no obvious risk factor identified) may have an underlying cancer. This should be performed in all patients, because there are few disadvantages and cancer can be effectively detected in up to half of all patients who present with VTE and have an underlying cancer.

18 Investigations for cancer (2)
First unprovoked DVT or PE? No signs or symptoms of cancer based on initial investigation? Over 40? Consider further investigations for cancer: abdomino-pelvic CT scan mammogram for women NOTES FOR PRESENTERS: Recommendation in full Consider further investigations for cancer with an abdomino-pelvic CT scan (and a mammogram for women) in all patients aged over 40 years with a first unprovoked DVT or PE who do not have signs or symptoms of cancer based on initial investigation (see recommendation on previous slide). [1.5.2] Additional information The GDG agreed that consideration of further investigations for cancer was most appropriate for patients over 40 years old with an apparently unprovoked VTE. The most effective and cost-effective investigations for cancer, that balance sensitivity and specificity, include abdominal/pelvic CT, mammography and sputum cytology (sputum cytology is not recommended, in line with NICE clinical guideline 121 ‘Treatment and diagnosis of lung cancer’). Studies suggest that among patients with VTE, the cancers most commonly found are in the abdomen and pelvic areas (ovary, pancreas, liver, kidney and colon).

19 Thrombophilia testing
X Do not offer to patients who are continuing anticoagulation treatment X Do not offer to patients who have had provoked DVT or PE X Do not routinely offer to first-degree relatives of people with a history of DVT or PE and thrombophilia Consider for patients with unprovoked PE or PE if it is planned to stop anticoagulation treatment NOTES FOR PRESENTERS: Recommendations in full Do not offer thrombophilia testing to patients who are continuing anticoagulation treatment. [1.6.1] Do not offer thrombophilia testing to patients who have had provoked DVT or PE. [1.6.4] Do not routinely offer thrombophilia testing to first-degree relatives of people with a history of DVT or PE and thrombophilia. [1.6.5] Consider testing for antiphospholipid antibodies in patients who have had unprovoked DVT or PE if it is planned to stop anticoagulation treatment. [1.6.2] Related recommendation Consider testing for hereditary thrombophilia in patients 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. [1.6.3] Additional information Thrombophilia is an acquired or inherited predisposition to venous thrombosis. The only important acquired thrombophilia is the presence of antiphospholipid antibodies (detected as a lupus anticoagulant or as antibodies against cardiolipin or β2-glycoprotein I). If a decision is made to continue anticoagulation treatment, it is unnecessary to offer thrombophilia testing as the results would not alter management. The additional risk associated with antiphospholipid syndrome is not large. Testing should therefore be considered only if, after assessment of the other risk factors in an individual patient with an unprovoked VTE, the plan is to stop anticoagulation (see recommendation 1.6.2). Thrombophilia testing for first degree relatives of people who have had thromboembolic disease and thrombophilia could theoretically lead to the reduction of VTE risk, if there are suitable interventions which can be applied to the relatives who are affected. However a family history of VTE increases a person’s risk of having a VTE whether they have a thrombophilia or not. These relatives would receive thromboprophylaxis in at risk situations; such as surgery, trauma or immobilisation. The test for hereditary thrombophilia should be offered to people of any age with unprovoked VTE who have a first degree relative with VTE, to reduce the risk of any patient who may have a hereditary thrombophilia being missed (see recommendation 1.6.3).

20 Discussion If not already common practice, how can we ensure we are able to offer immediate CTPA to eligible patients? Do we have the appropriate systems in place to ensure patients with a PE receive the appropriate follow up in order to assess continuation of LMWH and VKA? What referral systems do we have in place to facilitate the onward investigation for cancer and thrombophilia for patients with unprovoked PE? How do they need to be modified in order to meet the NICE recommendations? NOTES FOR PRESENTERS: These questions are suggestions that have been developed to help provide a prompt for a discussion at the end of your presentation – please edit and adapt these to suit your local situation. Additional questions How can we ensure clinicians have easy access to the two-level PE Wells score? How can we ensure that we provide the recommended patient information?

21 NICE quality standard for diagnosis and management of venous thromboembolic diseases
Published March 2013 Defines clinical best practice within this topic area. Provides specific, concise quality statements, measures and audience descriptors to provide the public, health and social care professionals, commissioners and service providers with definitions of high-quality care. Covers the diagnosis and treatment of venous thromboembolic diseases in adults, excluding pregnant women. NOTES FOR PRESENTERS: NICE quality standard for diagnosis and management of venous thromboembolic diseases Published in March This quality standard defines clinical best practice within this topic area. It provides specific, concise quality statements, measures and audience descriptors to provide the public, health and social care professionals, commissioners and service providers with definitions of high-quality care. This quality standard covers the diagnosis and treatment of venous thromboembolic diseases in adults, excluding pregnant women. If you are showing this presentation when connected to the internet, click on the orange button to go straight to the NICE quality standard for management of venous thromboembolic diseases or go to Click here to go to the NICE quality standard for management of venous thromboembolic diseases

22 NICE Evidence Services
Visit NICE Evidence Services for the best available evidence on all aspects of VTE diseases NOTES FOR PRESENTERS: If you are showing this presentation when connected to the internet, click on the orange button to go straight to the NICE Evidence Services website topic page for VTE diseases. For the home page go to Click here to go to the NICE Evidence Services website

23 Click here to go to the NICE Pathways website
The NICE VTE Pathway shows all the recommendations in the VTE diseases and VTE - reducing the risk guidelines. NOTES FOR PRESENTERS: Key points to raise The recommendations from this guideline have been incorporated into a NICE VTE pathway, which is available from If you are showing this presentation when connected to the internet, click on the orange button to go straight to the NICE Pathways website. The front page includes a two minute video giving an overview of the features and content within the site, as well as the list of topics covered. NICE Pathways: guidance at your fingertips Our new online tool provides quick and easy access, topic by topic, to the range of guidance from NICE, including quality standards, technology appraisals, clinical and public health guidance and NICE implementation tools. NICE pathways are simple to navigate and allow you to explore in increasing detail NICE recommendations and advice, giving you confidence that you are up to date with everything we have recommended. Click here to go to the NICE Pathways website

24 Find out more Visit http://guidance.nice.org.uk/CG144 for:
the guideline information for the public costing report audit support baseline assessment tool PE educational resource (training plan, slide set and clinical case scenarios) DVT educational resource (training plan, slide set and clinical case scenarios) podcast two-level wells score templates NOTES FOR PRESENTERS: You can download the guidance documents from the NICE website. The NICE guideline – all the recommendations. ‘Information for the public’ – information for patients and carers. The full guideline – all the recommendations, details of how they were developed, and reviews of the evidence they were based on. NICE has developed tools to help organisations implement this guideline, which can be found on the NICE website. Costing report – estimates the likely costs and savings anticipated when implementing the guideline. Clinical audit support with electronic data tools – for monitoring local practice. Baseline assessment tool – for assessing compliance against the guideline. PE educational resource – comprising of a training plan, slide set and clinical case scenarios – to support group and individual education and learning. DVT educational resource – comprising of a training plan, slide set and clinical case scenarios - to support group and individual education and learning. Podcast - Dr Roshan Agarwal, a member of the Guideline Development Group, discusses the venous thromboembolic diseases guidance and the link between VTE and cancer Two-level wells score templates – templates for local adaptation to allow the two-level Wells score for DVT or PE to be calculated and recorded in a format suitable for filing in the patient record.

25 What do you think? Did the implementation tool you accessed today meet your requirements, and will it help you to put the NICE guidance into practice? We value your opinion and are looking for ways to improve our tools. Please complete this short evaluation form. If you are experiencing problems accessing or using this tool, please NOTES FOR PRESENTERS: Additional information: This final slide is not intended to be part of the presentation. It asks for feedback on whether this implementation tool meets your requirements and whether it will help you to put this NICE guidance into practice: your opinion would be appreciated. To open the links in this slide set, right click over the link and choose ‘open link’. To open the links in this slide set right click over the link and choose ‘open link’

26 Additional slide The next slide contains the two-level PE Wells score
If you used the hyperlinks to the Wells score during the presentation you have already visited this slide Please note: The hyperlinks in this slide set should continue to work even if you add or remove slides. However, if you do add or remove slides we recommend that you check the links are still working afterwards.

27 Two-level PE Wells score
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 Heart rate > 100 beats per minute 1.5 Immobilisation more than 3 days/surgery in previous 4 weeks Previous DVT/PE Haemoptysis 1 Malignancy (on treatment/treated in the past 6 months/palliative) Clinical probability simplified scores PE likely More than 4 PE unlikely 4 or less a Adapted with permission from Wells PS et al. (2000) Derivation of a simple clinical model to categorize patients’ probability of pulmonary embolism: increasing the model’s utility with the SimpliRED D-dimer. Thrombosis and Haemostasis 83: 416–20 A template patient record Two-level PE Wells score, which you can print, complete and then add to patient records can be downloaded from the NICE website http://guidance.nice.org.uk/CG144/TemplateWellsScore/doc/English Return to slide 8 ‘Diagnostic investigations (1)’


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