Guideline sources The following summarized guidelines for the evaluation and management of pulmonary embolism are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2023; 2020), the Society for Vascular Medicine (SVM/AHA/ACC/ACS/ACCP/SIR 2020), the American Heart Association (AHA 2020), the European Society of Cardiology (ESC 2019), and the American College of Chest Physicians (ACCP 2016). 1 2 3 4 5 6 Calculator Calculator Calculat Bova score for pulmonary embol Caprini Score for venous thromb DASH s https://web.pathway.md/diseases/recshBNzK8Sf2asl9 1/12 6/29/23, 11:35 PM Pulmonary embolism Pathway Guidelines 1. Screening and diagnosis Diagnostic criteria: use validated diagnostic criteria in patients with suspected PE without hemodynamic instability. A 2. Classification and risk stratification Risk stratification: stratify patients with suspected or confirmed PE, based on the presence of hemodynamic instability, to identify patients at high risk of early mortality. A Show 2 more 3. Diagnostic investigations D-dimer: Obtain D-dimer testing, preferably with a highly sensitive assay, in outpatients/emergency department patients with low or intermediate clinical probability, or if the patient is PE- unlikely. A Do not obtain D-dimer testing in patients with high clinical probability, as a normal result does not safely exclude PE. D Diagnostic imaging: confirm the diagnosis of VTE if compression ultrasound shows a proximal DVT in a patient with clinical suspicion of PE. A Show 6 more 4. Medical management Setting of care: consider offering home treatment over hospital treatment for patients with PE with a low risk for complications. C Indications for anticoagulation: As per ESC 2019 guidelines, initiate anticoagulation while diagnostic workup is in progress in patients with suspected PE without hemodynamic instability and with high or intermediate clinical probability. A As per ACCP 2016 guidelines, complete at least 3 months of anticoagulant therapy in patients with proximal deep vein thrombosis or PE. B Show 3 more Choice of anticoagulation: As per ASH 2020 guidelines: Consider using direct OACs over vitamin K antagonists for patients with PE. C Insufficient evidence to suggest one direct OAC over another for patients with PE. I As per ESC 2019 guidelines, prefer a direct OAC if oral anticoagulation is initiated in patients with PE being eligible for a direct OAC (apixaban, dabigatran, edoxaban, or rivaroxaban). A https://web.pathway.md/diseases/recshBNzK8Sf2asl9 2/12 6/29/23, 11:35 PM Pulmonary embolism Pathway Show 4 more As per ACCP 2016 guidelines, consider dabigatran, rivaroxaban, apixaban, or edoxaban as long-term anticoagulant therapy, rather than vitamin K antagonist therapy, in patients with deep vein thrombosis of the leg or PE and no evidence of cancer. C Landmark trials: AMPLIFY In patients with acute VTE, apixaban was noninferior to warfarin with respect to recurrent symptomatic VTE or death related to VTE. Agnelli G et al. N Engl J Med. 2013 Aug 29. Duration of anticoagulation, unprovoked PE: As per ASH 2023 guidelines: Avoid obtaining thrombophilia testing to guide the duration of anticoagulant treatment after primary short-term treatment in patients with unprovoked VTE. D Avoid obtaining thrombophilia testing to guide anticoagulant treatment duration after primary short-term treatment in patients with an unspecified type of VTE. D As per ASH 2020 guidelines, consider completing a shorter course (3-6 months) over a longer (6-12 months) course of anticoagulation for primary treatment of patients with DVT and/or PE, whether provoked by a transient risk factor or by a chronic risk factor or unprovoked. C Show 2 more As per ESC 2019 guidelines, administer therapeutic anticoagulation for 3 months in all patients with PE (either provoked or unprovoked). A As per ACCP 2016 guidelines, administer anticoagulant therapy for at least 3 months in patients with an unprovoked PE. B Duration of anticoagulation, provoked PE: As per ASH 2023 guidelines, avoid obtaining thrombophilia testing to determine the duration of anticoagulant treatment after primary short-term treatment in patients with VTE provoked by surgery. D Show 2 more As per ASH 2020 guidelines, consider completing a shorter course (3-6 months) over a longer (6-12 months) course of anticoagulation for primary treatment of patients with DVT and/or PE, whether provoked by a transient risk factor or by a chronic risk factor or unprovoked. C Show 3 more As per ESC 2019 guidelines: Administer therapeutic anticoagulation for 3 months in all patients with PE (either provoked or unprovoked). A Discontinue therapeutic oral anticoagulation after 3 months in patients with a first episode of PE secondary to a major transient/reversible risk factor. A https://web.pathway.md/diseases/recshBNzK8Sf2asl9 3/12 6/29/23, 11:35 PM Pulmonary embolism Pathway As per ACCP 2016 guidelines, administer anticoagulant therapy for 3 months in patients with a proximal deep vein thrombosis of the leg or PE provoked by surgery. B Duration of anticoagulation (cancer-associated thrombosis): Initiate extended anticoagulant therapy (with no scheduled stop date) in patients with deep vein thrombosis of the leg or PE and active cancer and who do not have a high bleeding risk. B Consider initiating extended anticoagulant therapy (with no scheduled stop date) in patients with deep vein thrombosis of the leg or PE and active cancer who have a high bleeding risk. C Aspirin therapy post anticoagulation: As per ASH 2020 guidelines: Consider offering anticoagulation over aspirin in patients with PE who have completed primary treatment and will continue to receive secondary prevention. C Consider suspending aspirin over continuing it for the duration of anticoagulation therapy in patients with PE with stable CVD initiating anticoagulation and previously taking aspirin for cardiovascular risk modification. C As per ACCP 2016 guidelines, consider initiating aspirin to prevent recurrent VTE in patients with an unprovoked proximal deep vein thrombosis or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin. C Landmark trials: ASPIRE In patients who had completed initial anticoagulant therapy after a first episode of unprovoked VTE, aspirin was not superior to placebo with respect to the incidence of recurrent VTE. Brighton TA et al. N Engl J Med. 2012 Nov 22. Thrombolytic therapy: As per ASH 2020 guidelines, offer thrombolytic therapy followed by anticoagulation over anticoagulation alone for patients with PE and hemodynamic compromise. B Show 2 more As per ESC 2019 guidelines, administer systemic thrombolytic therapy in patients with high- risk PE. A Show 2 more As per ACCP 2016 guidelines, consider systemically administered thrombolytic therapy in patients with acute PE associated with hypotension (systolic BP < 90 mmHg) who do not have a high bleeding risk. C Landmark trials: PEITHO In normotensive patients with intermediate-risk PE, tenecteplase was superior to placebo with respect to death or hemodynamic decompensation at 7 days. https://web.pathway.md/diseases/recshBNzK8Sf2asl9 4/12 6/29/23, 11:35 PM Pulmonary embolism Pathway Meyer G et al. N Engl J Med. 2014 Apr 10. 5. Therapeutic procedures Indications for inferior vena cava filter placement: As per ASH 2020 guidelines, consider offering anticoagulation alone over anticoagulation plus insertion of an IVC filter in patients with PE and hemodynamic compromise. C As per SIR 2020 guidelines, consider placing an IVC filter based on various clinical risk factors in patients with acute PE with a contraindication to anticoagulation therapy. C Show 5 more As per ESC 2019 guidelines, do not perform routine placement of IVC filters in patients with PE. D As per ACCP 2016 guidelines, obtain placement of an IVC filter in patients with acute PE and a contraindication to anticoagulation. B Show 2 more Landmark trials: PREPIC 2 In hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis and at least 1 criterion for severity, IVC filter implantation was not superior to no IVC filter implantation with respect to symptomatic recurrent PE at 3 months. Mismetti P et al. JAMA. 2015 Apr 28. Anticoagulation with inserted inferior vena cava filter: as per ACCP 2016 guidelines, consider offering a conventional course of anticoagulant therapy in patients with acute PE and an IVC filter inserted as an alternative to anticoagulation, if their risk of bleeding resolves. C Systemic thrombolytic therapy: consider systemic thrombolytic therapy administered via a peripheral vein over catheter-directed thrombolysis in patients with acute PE who are treated with a thrombolytic agent. C Catheter-assisted thrombectomy: Consider catheter-assisted pulmonary artery thrombus removal, if appropriate expertise and resources are available, in patients with acute PE associated with hypotension who meet all the following criteria: high bleeding risk failure of systemic thrombolysis shock that is likely to cause death before systemic thrombolysis can take effect. C 6. Surgical interventions Surgical thromboendarterectomy: As per ESC 2019 guidelines, perform surgical pulmonary embolectomy in patients with high- risk PE if thrombolysis is contraindicated or has failed. A https://web.pathway.md/diseases/recshBNzK8Sf2asl9 5/12 6/29/23, 11:35 PM Pulmonary embolism Pathway As per ACCP 2016 guidelines, consider pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension who have been evaluated as appropriate candidates by an experienced thromboendarterectomy team. C 7. Specific circumstances Pregnant patients (antepartum thromboprophylaxis): Consider obtaining testing for the known familial thrombophilia in females with a family history of VTE and known homozygous factor V Leiden, a combination of factor V Leiden and prothrombin G20210A, or antithrombin deficiency in the family. Consider administering antepartum thromboprophylaxis in patients with the same familial thrombophilia. C Consider either obtaining testing for the known familial thrombophilia or omitting testing for thrombophilia to guide antepartum prophylaxis in females with a family history of VTE and known protein C or protein S deficiency in the family. C Pregnant patients (postpartum thromboprophylaxis): consider obtaining testing for the known familial thrombophilia in females with a first-degree family history of VTE and known homozygous factor V Leiden, a combination of factor V Leiden and prothrombin G20210A, antithrombin deficiency, protein C deficiency, or protein S deficiency in the family. Consider administering postpartum thromboprophylaxis in patients with the same familial thrombophilia. C Show 2 more Pregnant patients (evaluation): obtain a formal diagnostic assessment with validated methods in patients with suspected PE during pregnancy or in the postpartum period. A Pregnant patients, management of PE: As per ASH 2023 guidelines, consider obtaining thrombophilia testing to guide anticoagulant treatment duration after primary treatment in patients with VTE provoked by pregnancy or postpartum. Consider continuing anticoagulant treatment indefinitely in patients with thrombophilia and discontinuing it in patients without thrombophilia. C As per ESC 2019 guidelines, administer therapeutic, fixed doses of LMWH, based on early pregnancy weight, in the majority of pregnant patients without hemodynamic instability. A Show 3 more Patients with antiphospholipid syndrome: offer indefinite OAC therapy with a vitamin K antagonist in patients with antiphospholipid syndrome. A Patients with cardiac arrest: Consider performing thrombolysis, surgical embolectomy, or mechanical embolectomy as emergency treatment options in patients with confirmed PE as the precipitant of cardiac arrest. C Consider performing thrombolysis when cardiac arrest is suspected to be caused by PE. C 8. Preventative measures Thrombophilia testing for minor provoking factors: avoid obtaining testing for factor V Leiden or prothrombin G20210A (low-risk thrombophilia) to guide thromboprophylaxis in https://web.pathway.md/diseases/recshBNzK8Sf2asl9 6/12 6/29/23, 11:35 PM Pulmonary embolism Pathway patients with a family history of factor V Leiden (with or without VTE) and having a minor provoking risk factor for VTE, such as immobility or minor injury, illness, or infection. D Show 4 more Thrombophilia testing before hormone therapy (combined oral contraceptives): do not obtain thrombophilia testing to guide the use of combined oral contraceptives in females in the general population. D Show 3 more Thrombophilia testing before hormone therapy (hormone-replacement therapy): avoid obtaining thrombophilia testing to guide the use of hormone-replacement therapy in patients from the general population. D Show 3 more Anticoagulation for secondary prevention: Target an INR range of 2-3 over a lower range (such as 1.5-1.9) in patients with DVT and/or PE completed primary treatment and continuing vitamin K antagonist therapy for secondary prevention. B Consider using a standard- or a lower-dose direct OAC in patients with DVT and/or PE completed primary treatment and continuing direct OAC for secondary prevention. C 9. Follow-up and surveillance Indications for specialist referral: refer symptomatic patients with mismatched perfusion defects on V/Q lung scan beyond 3 months after acute PE to a pulmonary hypertension/chronic thromboembolic pulmonary hypertension expert centre, taking into account the results of echocardiography, natriuretic peptide, and/or cardiopulmonary exercise testing. A Follow-up: Obtain regular reassessments of drug tolerance and adherence, hepatic and renal function, and the bleeding risk in patients receiving extended anticoagulation. A Obtain routine reevaluation after 3-6 months in patients with acute PE. A Transition of care: implement an integrated model of care after acute PE, in order to ensure optimal transition from hospital to ambulatory care. A Management of recurrent pulmonary embolism: As per ASH 2020 guidelines: Consider administering LMWH over direct OAC therapy in patients with breakthrough DVT and/or PE during therapeutic vitamin K antagonist treatment. C Continue indefinite antithrombotic therapy over stopping anticoagulation after completion of primary treatment in patients with a recurrent unprovoked DVT and/or PE. B As per ESC 2019 guidelines, continue OAC therapy indefinitely in patients presenting with recurrent VTE (at least 1 previous episode of PE or DVT) not related to a major transient or reversible risk factor. A As per ACCP 2016 guidelines, consider switching to treatment with LMWH at least temporarily in patients who have recurrent VTE on OACs and are believed to be compliant. https://web.pathway.md/diseases/recshBNzK8Sf2asl9 7/12 6/29/23, 11:35 PM Pulmonary embolism Pathway C Clinical findings Symptoms Past medical history Acute cough COPD Anxiety Cancer Cardiac chest pain Crohn's disease Chest pain DVT Cough HF Coughing up blood IBD Dizziness Immobility Fainting Injury Hemoptysis Obesity LUQ pain Stroke Lightheadedness Family history Palpitations Poorly localized abdominal pain Family or personal history of blood clots RUQ pain Shortness of breath Vital signs Sudden chest pain Sweating Hypertension Hypotension Medication history Hypoxemia Estrogens Tachycardia Social history Cardiac exam Current cigarette smoking pulsus paradoxus Vascular exam ECG findings Leg edema Cardiac arrhythmias Low voltages Lab findings Pr depression or diffuse ST elevation Normal serum D-dimer RBBB Respiratory alkalosis S1q3t3 pattern serum D-dimer T wave inversion Imaging findings Findings of ovarian torsion Hampton hump Mcconnell's sign Palla's sign Subpleural infarct Westermark sign https://web.pathway.md/diseases/recshBNzK8Sf2asl9 8/12 6/29/23, 11:35 PM Pulmonary embolism Pathway RV di t Likelihood Ratios Pertinent positives The following findings increase the probability of pulmonary embolism in adults. 10 Finding LR+ Value Increased serum D-dimer* 1.7 (1.6-1.8) in patients at any pre-test probability of pulmonary embolism Pertinent negatives The following findings decrease the probability of pulmonary embolism in adults. 10 Finding LR- Value Abnormal serum D-dimer* 0.0 (0-0.06) in patients at low or moderate pre-test probability of pulmonary embolism Studies 2022 Diuretics in PE In patients with intermediate high-risk PE, diuretic therapy was superior to volume expansion with respect to time to b-type natriuretic peptide normalization. Emile Ferrari et al. Lung. 2022 Apr. 2021 MODIGLIA-NI In adult patients who had a low clinical risk of PE not excluded by the PE rule-out criteria rule or a subjective clinical intermediate risk of PE, modified diagnostic strategy was noninferior to a conventional diagnostic strategy with respect to VTE at 3 months. Yonathan Freund et al. JAMA. 2021 Dec 7. Show 22 more References 1. Kearon C, Akl EA, Ornelas J et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149 2 315 352. Open 2. Thomas L Ortel, Ignacio Neumann, Walter Ageno et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020 Oct 13;4 19 4693 4738. Open 3. 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