Pulmonary embolism treatment approach
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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-In-Chief: Kashish Goel, M.D.; Rim Halaby, M.D. [2]
Overview
Prompt recognition, diagnosis and treatment of pulmonary embolism is critical. Anticoagulant therapy is the mainstay of treatment for patients who are hemodynamically stable. If hemodynamic compromise is present, then fibrinolytic therapy is recommended.
Step 1: Confirm PE
Shown below is an algorithm depicting the initial diagnostic approach to pulmonary embolism.[1][2]
| Does the patient who is suspected to have PE have hypotension or shock? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Suspected high-risk PE | Suspected non-high risk PE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Is a CT available immediately? | What is the pretest probability of PE? Assess the pretest probability of PE by using one of the risk score: - Wells score - Geneva score - PERC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Order echocardiography | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Does the patient have RV overload? | Low pretest probability | Intermediate pretest probability | High pretest probability OR PE is likely | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | Order CT | Order D-dimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive | Negative | Positive | Negative | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Is the patient unstable OR no other tests are available? | Is the patient stabilized AND CT is now available? | Order CT | PE is excluded | Order CT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive | Negative | Positive | Negative | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PE is excluded | Consider thrombolytic therapy or embolectomy | Order CT | PE is confirmed | PE is excluded | PE is confirmed | PE is excluded | PE is confirmed | PE is excluded | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive for PE | Negative for PE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PE is confirmed | PE is excluded | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Step 2: Initial Treatment
Shown below is an algorithm depicting the initial management of pulmonary embolism.[1][2]
| Assess the severity of pulmonary embolism | |||||||||||||||||||||||||||||||||||||||||||||||||
| Massive PE (also known as high-risk PE) Cardiogenic shock OR Persistent hypotension (≤90mmHg) OR Drop of the blood pressure by ≥ 40mmHg for > 15 min[3] OR Pulselessness OR Profound bradycardia (<40 bpm) with findings of shock[4] | Submassive PE (also know as intermediate-risk PE) Right ventricular dysfunction AND/OR Myocardial injury (Troponin +) | Low-risk PE No cardiogenic shock AND No hypotension AND No right ventricular dysfunction AND No myocardial injury (Troponin -) | |||||||||||||||||||||||||||||||||||||||||||||||
| Provide hemodynamic and respiratory support Begin high dose unfractionated heparin [3]: Bolus 10.000 U
Administer rapidly 500-1000 mL of normal saline (Caution with fluid overload)[3] | |||||||||||||||||||||||||||||||||||||||||||||||||
| Is there any contraindication for fibrinolytic therapy? | Is there any contraindication for anticoagulation therapy? | Is there any contraindication for anticoagulation therapy? | |||||||||||||||||||||||||||||||||||||||||||||||
| NO | YES | NO | YES | NO | YES | ||||||||||||||||||||||||||||||||||||||||||||
| Discontinue unfractionated heparin AND Begin fibrinolytic therapy | Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Anticoagulation therapy AND Hospital admission | IVC filter AND Hospital admission | Anticoagulation therapy AND Early discharge/home treatment | IVC filter AND Early discharge/home treatment | ||||||||||||||||||||||||||||||||||||||||||||
| Does the patient fail to improve OR Develop cardiogenic shock? OR Develop hypotension? | Does the patient fail to improve OR Develop cardiogenic shock? OR Develop hypotension (<90 mmHg)? OR Develop respiratory distress (SaO2<95% with Borg score>8 or altered mental status) OR Have moderate to severe RV dysfunction (RV hypokinesis or estimated RVSP>40 mmHg) OR Elevated biomarkers (troponin> upper limit of normal, BNP>100 pg/mL, or pro-BNP>900 pg/mL)[4] | ||||||||||||||||||||||||||||||||||||||||||||||||
| YES | NO | YES | NO | ||||||||||||||||||||||||||||||||||||||||||||||
| Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Continue with the same treatment | Is there any contraindication for fibrinolytic therapy? | Continue with the same treatment | ||||||||||||||||||||||||||||||||||||||||||||||
| NO | YES | ||||||||||||||||||||||||||||||||||||||||||||||||
| Hold anticoagulation and give thrombolytics | Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | ||||||||||||||||||||||||||||||||||||||||||||||||
| Does the patient fail to improve? | |||||||||||||||||||||||||||||||||||||||||||||||||
| YES | NO | ||||||||||||||||||||||||||||||||||||||||||||||||
| Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Continue with the same treatment | ||||||||||||||||||||||||||||||||||||||||||||||||
Anticoagulation Therapy
Initial Anticoagulation Therapy
Begin initial anticoagulation therapy in: ❑ Confirmed PE OR ❑ High or intermediate probability of PE while awaiting the diagnostic tests | |||||||||||||||||||||||
Is the patient high risk or non-high risk? | |||||||||||||||||||||||
| High risk | Non-high risk | ||||||||||||||||||||||
❑ Administer IV unfractionated heparin[5]
| |||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||
❑ Administer ONE of the following:[5]
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Long Term Anticoagulation Therapy
The long term management of PE depends on whether the episode is the first one or not, whether it is provoked or unprovoked, and on the risk of bleeding of the patient. Among non cancer patients, the first line therapy for long term management of PE is vitamin K antagonists (VKA); whereas the first line treatment among cancer patients is low molecular weight heparin. If long term treatment with VKA is decided, VKA should be started at the same day with heparin allowing for at least 5 days of overlap until the INR is ≥2 for at least 24 hours. Among patients on extended anticoagulation therapy, the risk vs benefits of the anticoagulation therapy should be assessed regularly (for example annually).[2]
| Is this the first episode of PE? | |||||||||||||||||||||||||||||||||||||||
| YES | NO | ||||||||||||||||||||||||||||||||||||||
| Is PE provoked? | What is the risk of bleeding? | ||||||||||||||||||||||||||||||||||||||
| Yes, transient reversible risk factor | Yes, cancer | No (unprovoked) | Low or moderate | High | |||||||||||||||||||||||||||||||||||
| Therapy for 3 months | Extended therapy or until cancer is cured | Therapy for ≥ 3 months | Extended therapy | Therapy for 3 months | |||||||||||||||||||||||||||||||||||
| Re-assess the risk of bleeding | |||||||||||||||||||||||||||||||||||||||
| Low or moderate | High | ||||||||||||||||||||||||||||||||||||||
| Extended therapy | Do not extend the therapy beyond the initial 3 months | ||||||||||||||||||||||||||||||||||||||
Note that edoxaban[6] has been evaluated for the treatment of VTE and is currently seeking approval for this indication.
Step 3: Long Term Treatment
- After treatment in the hospital, the patient should continue anticoagulation treatment for 3 months if the PE is provoked by surgery or a nonsurgical transient risk factor.
- An abnormal D-dimer level at the end of the treatment course might signal the need for continued treatment with anticoagulation for a first time unprovoked pulmonary embolus.[7]
- Long-term treatment is usually recommended with vitamin K antagonists like warfarin, unless contraindicated or some special circumstances.
- The recommended therapeutic INR range for patients with PE is 2.0-3.0.
- Continued warfarin administration needs close monitoring. The patient should have an appointment with the "anticoagulation clinic" before leaving the hospital.
Extended Anticoagulation
Extended Treatment means extending the anticoagulation therapy beyond the first 3 months. It is recommended in the following scenarios:
- For a pulmonary embolism that is unprovoked. The patient's risk should be re-evaluated at 3 months to consider whether or not extended therapy is warranted.
- Active cancer.
- Recurrent venous thromboembolism.
- Chronic thrombembolic pulmonary hypertension.
Salient Features:
- For extended therapy, the continued need for anticoagulation and the risk-benefit ratio should be re-evaluated at periodic intervals (eg, annually).
- Patients with recurrent thromboembolic disease, with or without anticoagulation, should be evaluated for possible thrombophilias.
Specific Circumstances
- Malignancy: Low molecular weight heparin is favored over warfarin based on the results of the CLOT trial.[8]
- Pregnancy: Low molecular weight heparin is preferred to avoid the known teratogenic effects of warfarin.
- Asymptomatic patients who are diagnosed with an incidental PE should be managed with the same criteria as those with symptomatic PE.
Newer Anticoagulants
- Dabigatran (direct thrombin inhibitor), Rivaroxaban (Factor Xa inhibitor), and other drugs in the same classes, provide an alternate option to warfarin/LMWH for treatment of PE.
- Advantages include the availability of an oral formulation, no frequent monitoring requirement, a predictable effect profile, and few (known) drug interactions.
- Disadvantages include the currently limited prospective trial data, the theoretical interaction with statins (as they are metabolized by the same CYP3A4 enzyme), and the risk of bleeding.
References
- ↑ 1.0 1.1 1.2 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)". Eur Heart J. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
- ↑ 2.0 2.1 2.2 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ; et al. (2012). "Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e419S–94S. doi:10.1378/chest.11-2301. PMC 3278049. PMID 22315268.
- ↑ 3.0 3.1 3.2 3.3 3.4 Kucher N, Goldhaber SZ (2005). "Management of massive pulmonary embolism". Circulation. 112 (2): e28–32. doi:10.1161/CIRCULATIONAHA.105.551374. PMID 16009801.
- ↑ 4.0 4.1 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ; et al. (2011). "Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association". Circulation. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387.
- ↑ 5.0 5.1 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
- ↑ Hokusai-VTE Investigators. Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S; et al. (2013). "Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism". N Engl J Med. 369 (15): 1406–15. doi:10.1056/NEJMoa1306638. PMID 23991658. Review in: Ann Intern Med. 2014 Jan 21;160(2):JC4 Review in: Ann Intern Med. 2014 Mar 18;160(6):JC4
- ↑ Palareti G, Cosmi B, Legnani C; et al. (2006). "D-dimer testing to determine the duration of anticoagulation therapy". N. Engl. J. Med. 355 (17): 1780–9. doi:10.1056/NEJMoa054444. PMID 17065639.
- ↑ Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003). "Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer". N Engl J Med. 349 (2): 146–53. PMID 12853587.