Pulmonary embolism overview: Difference between revisions
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Contrast pulmonary angiography is the gold standard when diagnosing a PE. The disadvantages of using pulmonary angiography are its invasiveness, high costs, limited availability, and the need of an expert radiologist. This chapter deals with the advantages of multidetector CT over CTPA. | Contrast pulmonary angiography is the gold standard when diagnosing a PE. The disadvantages of using pulmonary angiography are its invasiveness, high costs, limited availability, and the need of an expert radiologist. This chapter deals with the advantages of multidetector CT over CTPA. | ||
=== CT Pulmonary Angiography === | |||
[[Computed tomography]] with [[radiocontrast]] is the imaging modality of choice in the diagnosis of pulmonary embolism. | |||
=== MRI === | === MRI === | ||
Revision as of 20:45, 5 February 2013
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Pulmonary Embolism Microchapters |
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Diagnosis |
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Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores |
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Treatment |
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Follow-Up |
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Special Scenario |
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Trials |
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Case Studies |
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Pulmonary embolism overview On the Web |
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Directions to Hospitals Treating Pulmonary embolism overview |
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Risk calculators and risk factors for Pulmonary embolism overview |
Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Pulmonary embolism (PE) is an acute obstruction of the pulmonary artery (or one of its branches). The obstruction in the pulmonary artery that causes a PE can be due to thrombus, air, tumor, or fat. Most often, this is due to a venous thrombosis (blood clot from a vein), which has been dislodged from its site of formation in the lower extremities. It has then embolized to the arterial blood supply of one of the lungs. This process is termed thromboembolism. PE is a potentially lethal condition. The patient can present with a range of signs and symptoms, including dyspnea, chest pain while breathing, and in more severe cases collapse, shock, and cardiac arrest. PE treatment requires rapid and accurate risk stratification before the development of hemodynamic collapse and cardiogenic shock. Treatment consists of an anticoagulant medication, such as heparin or warfarin, and in severe cases, thrombolysis or surgery. Pulmonary embolism can be classified based on the time course of symptom presentation (acute and chronic) and the overall severity of disease (stratified based upon three levels of risk: massive, submassive, and low-risk).
Historical Perspective
Throughout history, many renowned researchers and health care professionals have contributed to the understanding, definition, and treatment of pulmonary embolism. Though the first documented case of pulmonary embolism occurred in 1837, historical record of thrombotic disease dates as far back as the 7th century BCE.[1]
Classification
Pulmonary embolism can be classified based on the time course of symptom presentation (acute and chronic) and the overall severity of disease (stratified based upon three levels of risk: massive, submassive, and low-risk).
Pathophysiology
Pulmonary embolism occurs when there is an acute obstruction of the pulmonary artery or one of its branches. It is commonly caused by a venous thrombus that has dislodged from its site of formation and embolized to the arterial blood supply of one of the lungs. The process of clot formation and embolization is termed thromboembolism.
Differentiation of Pulmonary Embolism from other Disorders
Pulmonary embolism must be distinguished from other life-threatening causes of chest pain including acute myocardial infarction, aortic dissection, and pericardial tamponade, as well as a large list of non-life-threatening causes of chest discomfort and shortness of breath.
Epidemiology and Demographics
Each year in United States, there are between 300,000-600,000 cases of pulmonary embolism (PE). The prevalence of the disease increases as age increases.
Risk Factors
The most common sources of pulmonary emboli are proximal leg deep venous thromboses (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk of pulmonary embolism, and therefore DVT and PE are considered to be a continuum termed venous thromboembolism (VTE). Approximately 15% of patients with a DVT will develop a pulmonary embolus. Smoking, estrogen-containing hormonal contraceptives, and immobilization (including long distance travel) are common risk factors.
Natural History, Complications and Prognosis
Pulmonary embolism can be acutely complicated by the development of cardiogenic shock, pulseless electrical activity and sudden cardiac death and chronically by the development of pulmonary hypertension. The medical management of pulmonary embolism often requires the administration of potent parenteral anticoagulants and fibrinolytics and massive bleeding can be a complication of their administration. If left untreated almost one-third of patients with pulmonary embolism die, typically from recurrent pulmonary embolism. However, with prompt diagnosis and treatment, the mortality rate is approximately 2–8%. The true mortality associated with pulmonary embolism may be underestimated as two-thirds of all pulmonary embolism cases are diagnosed by autopsy.
Diagnosis
Assessment of Clinical Probability
The diagnosis of pulmonary embolism is based primarily on the clinical evaluation combined with diagnostic modalities such as spiral CT, V/Q scan, use of the D-dimer and lower extremity ultrasound. Although the clinical pretest probability has shown to be fairly accurate,[2] the lack of validation has led to the use of a combination of both clinical and diagnostic variables. These variables predict the pretest probability that aids in the immediate management of high-risk patients.
History and Symptoms
The symptoms of pulmonary embolism (PE) depends on the severity of the disease. A Pulmonary embolism may be an incidental finding in so far as many patients are asymptomatic.[3][4] The common symptoms of PE range from mild dyspnea, chest pain, and tachypnea, to sustained hypotension and shock.[5][4] The absence of these symptoms may be associated with a reduced clinical probability of pulmonary embolism, however it does not exclude the diagnosis of pulmonary embolism. The symptoms of lower extremity deep venous thrombosis may also be present.
Physical Examination
Pulmonary emboli are associated with the presence of tachycardia and tachypnea. Signs of right ventricular failure include jugular venous distension, a right sided S3, and a parasternal lift. These signs are often present in cases of massive pulmonary emboli.[5]
Laboratory Findings
The results of routine laboratory tests including arterial blood gas analysis are non-specific in making the diagnosis of pulmonary embolism. These laboratory studies can be obtained to rule-out other cause of chest discomfort and tachypnea. In patients with acute pulmonary embolism, non-specific lab findings include: leukocytosis, elevated ESR with an elevated serum LDH and serum transaminase (especially AST or SGOT).
Arterial Blood Gas Analysis
Hypoxemia, hypocapnia, increased alveolar-arterial gradient, and respiratory alkalosis are common findings that may be observed in patients with pulmonary embolism. In patients with suspected PE, Rodger et al, demonstrated that ABG analysis did not have sufficient negative predictive value, specificity, or likelihood ratios to be considered useful in the management these patients.[6] Similar findings were observed by the PIOPED II investigators.[7]
D-Dimer
D-dimer is a fibrin degradation product. D-dimer levels are elevated in the plasma after the acute formation of a blood clot. The majority of patients with pulmonary embolism have some degree of endogenous fibrinolysis with an elevation in D-dimer levels, therefore there is a high negative predictive value in ruling out a pulmonary embolism when D-dimer levels are low. However a wide range of diseases are associated with mild degree of fibrinolysis which elevate D-dimer levels and contribute towards a reduced specificity and a poor positive predictive value of a high D-dimer level. This means that it is more likely that one can rule out a PE with a low D-dimer level, but cannot necessarily confirm the diagnosis of a PE based on a high D-dimer level. Other disease states that can also have a high d-dimer level include pneumonia, congestive heart failure (CHF), myocardial infarction (MI) and malignancy. False-negative values may occur in patients with prolonged symptoms of venous thromboembolism (≥14 days), patients on therapeutic heparin therapy, and patients with suspected deep venous thrombosis on oral anticoagulation, as these patients have will have low D-dimer levels in the presence of a PE.[8][4]
Biomarkers
Although the success of brain natriuretic peptide levels to diagnose pulmonary embolism is limited due to the reduced sensitivity of the test,[9] elevated BNP and pro-BNP levels accurately predict right ventricular dysfunction and associated mortality, and are therefore useful prognostic markers. [4] The evaluation of troponin levels also serves as a useful prognostic marker to identify right ventricular myocardial injury[10][11] and mortality associated with acute pulmonary embolism.[12]
Electrocardiogram
EKG abnormalities in the setting of pulmonary emolism are non-specific.[13][14] The EKG may also lack sensitivity as the EKG may be normal in the setting of a pulmonary embolus. In a prospective study EKG abnormalities were present in 70% of patients with documented acute pulmonary embolism. The most common EKG abnormality was nonspecific ST-segment and T-wave changes.[15] An electrocardiogram (ECG) is routinely performed in all patients with chest pain to assess for a myocardial infarction, but the diagnosis of a pulmonary embolism should be kept in mind as well.
Chest X Ray
A chest X ray is often obtained in patients with shortness of breath to diagnose pneumonia, congestive heart failure, and rib fracture. Although the chest X ray in the setting of a pulmonary embolism is often abnormal, the findings are non-specific and are not diagnostic of a pulmonary embolus.[16]
Ventilation/Perfusion Scan
A ventilation/perfusion scan (otherwise known as V/Q scan or lung scintigraphy) is a study which shows whether an area of the lung is being ventilated with oxygen and perfused with blood. In the setting of a PE, perfusion can be obstructed due to the formation of a clot. The V/Q scan is less commonly used due to the more widespread availability of CT technology, however it may be useful in patients who have an allergy to iodinated contrast. It may also be useful in pregnant patients in an attempt to minimize radiation exposure.
Echocardiography
Approximately 40% of patients with pulmonary embolism have evidence of right heart strain on echocardiography. When RV dysfunction or RV thrombus are identified on echocardiography, this finding provides further risk stratification. Routine echocardiography in patients with suspected pulmonary embolism is not required. However if elevations in the cardiac troponins or brain natriuretic peptide are present, then acute right ventricular strain may be present and echocardiography may be warranted.[17]
Compression Ultrasonography
Compression Ultrasonography, also known as a Doppler study of the legs, or lower extremity noninvasive studies (LENIS) is used to evaluate a patient for the presence of deep venous thrombosis (DVT) in the lower extremities, which can lead to the development of a pulmonary embolism. The presence of a DVT shown by ultrasonography is enough to warrant anticoagulation without a V/Q or spiral CT scans. The decision to anticoagulant patient with a positive compression ultrasound is due to the strong association between deep vein thrombosis and subsequent pulmonary embolism. Compression ultrasonography is also a preferred method of evaluation during pregnancy, a time during which the other modalities would increase the risk of birth defects due to radiation exposure. A negative compression ultrasound does not rule out a pulmonary embolism, and an additional low-radiation dose scanning may be required in a pregnant patient to further rule out pulmonary embolism.
CT
Contrast pulmonary angiography is the gold standard when diagnosing a PE. The disadvantages of using pulmonary angiography are its invasiveness, high costs, limited availability, and the need of an expert radiologist. This chapter deals with the advantages of multidetector CT over CTPA.
CT Pulmonary Angiography
Computed tomography with radiocontrast is the imaging modality of choice in the diagnosis of pulmonary embolism.
MRI
Magnetic resonance pulmonary angiography should be considered in the setting of a pulmonary embolism only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. MRA has a sensitivity and specificity of 78% and 99% respectively.[18]
Prompt recognition, diagnosi and treatment of pulmonary embolism is criticl. Anticoagulant therapy is the mainstay of treatment for patients who are hemodynamically stable. If hemodynamic compromise is present, then fibrinolytic therapy is recommended.
Treatment Algorithm
Step 1: Establish The Diagnosis Of Pulmonary Embolism
In hospitals that have experience in performing and interpreting CT pulmonary angiography, the following flowchart approach can be adopted.
| Determine chances of PE | |||||||||||||||||||||||||||||||||
| Low chance | High chance | ||||||||||||||||||||||||||||||||
| D-dimer | |||||||||||||||||||||||||||||||||
| <500 ng/ml | >500 ng/ml | CT Pulmonary angiography | |||||||||||||||||||||||||||||||
| PE excluded | Negative | Positive | |||||||||||||||||||||||||||||||
| PE excluded | PE confirmed | ||||||||||||||||||||||||||||||||
Note: If there is a high clinical suspicion of pulmonary embolism, then anticoagulation can begin with a parenteral agent such as unfractionated heparin during the process of performing the diagnostic studies.
Step 2: Use A Risk-Stratified Approach to Treat the Patient with Pulmonary Embolism
| Confirmed PE | |||||||||||||||||||||||||||||||||||||||||||||||
| Assess Clinical Stability | |||||||||||||||||||||||||||||||||||||||||||||||
| Unstable | Stable | ||||||||||||||||||||||||||||||||||||||||||||||
| Blood Pressure =< 90mm Drop >=40mm for > 15 min | Assess RV function Biomarkers of injury | ||||||||||||||||||||||||||||||||||||||||||||||
| Thrombolysis Catheter embolectomy Surgery | No Dysfunction No Injury | Dysfunction No Injury | Dysfunction + Injury | ||||||||||||||||||||||||||||||||||||||||||||
| Anticoagulate Early Discharge | Anticoagulate Ward admit | ICU/Thrombolytics | |||||||||||||||||||||||||||||||||||||||||||||
Low Risk Pulmonary Embolism
Low-risk PE: Therapeutic anticoagulation, unless contraindicated.
Sub Massive Pulmonary Embolism
Submassive PE: If the patient is hemodynamically stable without major RV dysfunction or infarction, therapeutic anticoagulation should be started. In some cases, thrombolysis may be indicated.
Massive Pulmonary Embolism
Massive PE: Thrombolysis is indicated and ICU admission may be required. Initial supportive therapies for these patients may include:
- Respiratory support with oxygen for hypoxemic patients and mechanical ventilation in cases of severe hypoxemia or pending respiratory failure.
- Hemodynamic support with intravenous fluids or intravenous vasopressors is indicated for hypotensive patients. Intravenous fluids should be administered with caution as increased right ventricular load can disable the oxygen balance.[19]
- If anticoagulation is contraindicated, then an IVC filter is recommended.
Step 3: Assess Treatment Response and Need for Device Based Therapy
| Acute PE confirmed | |||||||||||||||||||||||||||||||||||||||||||||||
| Anticoagulation contraindicated ? | |||||||||||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||
| IVC filter | Risk Stratification | ||||||||||||||||||||||||||||||||||||||||||||||
| Low-risk PE | Submassive PE | Massive PE | |||||||||||||||||||||||||||||||||||||||||||||
| Anticoagulation | Anticoagulation | ||||||||||||||||||||||||||||||||||||||||||||||
| Assess clinically for evidence of increased severity | |||||||||||||||||||||||||||||||||||||||||||||||
| Evidence of Shock (SBP <90 mmHg) or respiratory failure | Is Thrombolytic Contraindicated? | ||||||||||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||
| Surgical emblectomy or catheter based interventions | Hold Anticoagulation, Give Thrombolytics then resume Anticoagulations | ||||||||||||||||||||||||||||||||||||||||||||||
| Patient shows clinical improvement | |||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | ||||||||||||||||||||||||||||||||||||||||||||||
| Surgical emblectomy or catheter based interventions | Continue anticoagulation | ||||||||||||||||||||||||||||||||||||||||||||||
Acute Therapies
Anticoagulation
The most common cause of mortality in patients with a pulmonary embolism, is a recurrent PE occurring within a few hours of the initial event.[20] Anticoagulation prevents further clot formation and extension, therefore it should be started as early as possible. Anticoagulation does not disaggregate existing clot, but it does facilitate the action of the body's endogenous lytic system. Anticoagulation is the cornerstone of therapy in an acute pulmonary embolism.[20][21] After initial risk stratification. Certain conditions like pericardial tamponade and aortic dissection can mimic pulmonary embolism. The use of anticoagulants is contraindicated in these medical conditions. Proceed with caution if these conditions are high on the differential. Immediate treatment should be initiated based on the following guidelines: [22][23][24]
- Initial treatment with parenteral anticoagulants, including subcutaneous low molecular weight heparin (such as enoxaparin and dalteparin), subcutaneous fondaparinux, or intravenous unfractionated heparin, should be administered unless contraindicated.
- ACCP guidelines[22] recommend low molecular weight heparin or fondaparinux instead of intravenous unfractionated heparin.
- If there is moderate-to-high clinical suspicion of a PE, anticoagulation should be initiated while awaiting confirmatory tests.
- Vitamin K antagonists such as warfarin should be started the same day. Parenteral anticoagulation should be continued for at least 5 days, and preferably until INR is 2.0 or above for 1-2 days.
- Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, the INR goal should be between 2.0 and 3.0.
- In patients with suspected or confirmed heparin-induced thrombocytopenia, lepirudin or argatroban should be used.
Thrombolysis
- Unless previously contraindicated, thrombolysis is indicated in patients with a massive PE or those with a submassive PE who develop or are at risk of developing hypotension (SBP < 90 mmHg).
- Administration of a fibrinolytic via a peripheral intravenous catheter is recommended.
- FDA recommends a 100 mg dose of alteplase administered as a continuous infusion over 2 hours. This treatment is supported by AHA[23] and ACCP guidelines.[22]
- Withhold anticoagulation during the 2 hours of fibrinolytic infusion.
- The role of thrombolysis in a submassive PE is not established at this point.[25] Two ongoing trials are investigating the efficacy and safety of this approach.
- No large clinical trial has demonstrated a mortality benefit of thrombolytic therapy. However, it helps by accelerating clot lysis, improving pulmonary perfusion, and improving right ventricular function.[26][27]
To read more about dosage, contraindications, and guidelines, click here.
Surgical procedures
- Catheter-assisted thrombus removal is recommended in patients with a massive PE who have contraindications to thrombolytic therapy or have failed thrombolysis.
- Thrombectomy is also recommended for patients who are in severe shock that may cause the patient to die before thrombolysis takes effect (hours).
- Pulmonary embolectomy is also recommended if a patient with the above conditions fails catheter-assisted embolectomy.
IVC filter
- An IVC filter is indicated for patients for whom anticoagulation is contraindicated.
- Anticoagulation should be restarted once the contraindication is resolved.
Chronic Therapies
- 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.[28]
- 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.[29]
- 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
- ↑ Wood KE (2009). "A history of pulmonary embolism and deep venous thrombosis". Crit Care Clin. 25 (1): 115–31, viii. doi:10.1016/j.ccc.2008.12.014. PMID 19268798.
- ↑ "Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators". JAMA : the Journal of the American Medical Association. 263 (20): 2753–9. 1990. PMID 2332918.
|access-date=requires|url=(help) - ↑ Stein PD, Matta F, Musani MH, Diaczok B (2010). "Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review". The American Journal of Medicine. 123 (5): 426–31. doi:10.1016/j.amjmed.2009.09.037. PMID 20399319. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ 4.0 4.1 4.2 4.3 Agnelli G, Becattini C (2010). "Acute pulmonary embolism". The New England Journal of Medicine. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Stein PD, Beemath A, Matta F, Weg JG, Yusen RD, Hales CA, Hull RD, Leeper KV, Sostman HD, Tapson VF, Buckley JD, Gottschalk A, Goodman LR, Wakefied TW, Woodard PK (2007). "Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II". The American Journal of Medicine. 120 (10): 871–9. doi:10.1016/j.amjmed.2007.03.024. PMC 2071924. PMID 17904458. Retrieved 2012-04-26. Unknown parameter
|month=ignored (help) - ↑ Rodger MA, Carrier M, Jones GN, Rasuli P, Raymond F, Djunaedi H, Wells PS (2000). "Diagnostic value of arterial blood gas measurement in suspected pulmonary embolism". American Journal of Respiratory and Critical Care Medicine. 162 (6): 2105–8. PMID 11112122. Retrieved 2012-04-30. Unknown parameter
|month=ignored (help) - ↑ Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2006). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators". The American Journal of Medicine. 119 (12): 1048–55. doi:10.1016/j.amjmed.2006.05.060. PMID 17145249. Retrieved 2012-04-30. Unknown parameter
|month=ignored (help) - ↑ Bruinstroop E, van de Ree MA, Huisman MV (2009). "The use of D-dimer in specific clinical conditions: a narrative review". Eur J Intern Med. 20 (5): 441–6. doi:10.1016/j.ejim.2008.12.004. PMID 19712840.
- ↑ Söhne M, Ten Wolde M, Boomsma F, Reitsma JB, Douketis JD, Büller HR (2006). "Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism". Journal of Thrombosis and Haemostasis : JTH. 4 (3): 552–6. doi:10.1111/j.1538-7836.2005.01752.x. PMID 16405522. Retrieved 2012-05-01. Unknown parameter
|month=ignored (help) - ↑ Meyer T, Binder L, Hruska N, Luthe H, Buchwald AB (2000). "Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction". Journal of the American College of Cardiology. 36 (5): 1632–6. PMID 11079669. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Horlander KT, Leeper KV (2003). "Troponin levels as a guide to treatment of pulmonary embolism". Current Opinion in Pulmonary Medicine. 9 (5): 374–7. PMID 12904706. Retrieved 2012-05-02. Unknown parameter
|month=ignored (help) - ↑ Jiménez D, Díaz G, Molina J, Martí D, Del Rey J, García-Rull S; et al. (2008). "Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism". Eur Respir J. 31 (4): 847–53. doi:10.1183/09031936.00113307. PMID 18094010.
- ↑ Geibel A, Zehender M, Kasper W, Olschewski M, Klima C, Konstantinides SV (2005). "Prognostic value of the ECG on admission in patients with acute major pulmonary embolism". Eur Respir J. 25 (5): 843–8. doi:10.1183/09031936.05.00119704. PMID 15863641.
- ↑ Rodger M, Makropoulos D, Turek M, Quevillon J, Raymond F, Rasuli P; et al. (2000). "Diagnostic value of the electrocardiogram in suspected pulmonary embolism". Am J Cardiol. 86 (7): 807–9, A10. PMID 11018210.
- ↑ Stein PD, Saltzman HA, Weg JG (1991). "Clinical characteristics of patients with acute pulmonary embolism". Am J Cardiol. 68 (17): 1723–4. PMID 1746481.
- ↑ Worsley D, Alavi A, Aronchick J, Chen J, Greenspan R, Ravin C (1993). "Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study". Radiology. 189 (1): 133–6. PMID 8372182.
- ↑ Kucher N, Goldhaber SZ (2003). "Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism". Circulation. 108 (18): 2191–4. doi:10.1161/01.CIR.0000100687.99687.CE. PMID 14597581.
- ↑ Meaney JF, Weg JG, Chenevert TL, Stafford-Johnson D, Hamilton BH, Prince MR (1997). "Diagnosis of pulmonary embolism with magnetic resonance angiography". N. Engl. J. Med. 336 (20): 1422–7. doi:10.1056/NEJM199705153362004. PMID 9145679. Retrieved 2011-12-14. Unknown parameter
|month=ignored (help) - ↑ Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H (1999). "Hemodynamic effects of fluid loading in acute massive pulmonary embolism". Crit. Care Med. 27 (3): 540–4. PMID 10199533. Retrieved 2011-12-12. Unknown parameter
|month=ignored (help) - ↑ 20.0 20.1 Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE (1992). "The clinical course of pulmonary embolism". N. Engl. J. Med. 326 (19): 1240–5. doi:10.1056/NEJM199205073261902. PMID 1560799. Retrieved 2011-12-12. Unknown parameter
|month=ignored (help) - ↑ Goldhaber SZ, Visani L, De Rosa M (1999). "Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER)". Lancet. 353 (9162): 1386–9. PMID 10227218. Retrieved 2011-12-12. Unknown parameter
|month=ignored (help) - ↑ 22.0 22.1 22.2 Kearon C, Akl EA, Comerota AJ; 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. PMID 22315268. Unknown parameter
|month=ignored (help) - ↑ 23.0 23.1 Jaff MR, McMurtry MS, Archer SL; 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. Unknown parameter
|month=ignored (help) - ↑ Torbicki A, Perrier A, Konstantinides S; 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. Unknown parameter
|month=ignored (help) - ↑ Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2006;(2):CD004437. PMID 16625603.
- ↑ Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W (2002). "Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism". N. Engl. J. Med. 347 (15): 1143–50. doi:10.1056/NEJMoa021274. PMID 12374874. Retrieved 2011-12-13. Unknown parameter
|month=ignored (help) - ↑ Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M (1990). "A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism". Chest. 98 (6): 1473–9. PMID 2123152. Retrieved 2011-12-21. Unknown parameter
|month=ignored (help) - ↑ 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.