Pulmonary embolism differential diagnosis: Difference between revisions

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| <figure-inline><figure-inline>[[File:Siren.gif|link=Pulmonary embolism resident survival guide|41x41px]]</figure-inline></figure-inline>|| <br> || <br>
| <figure-inline><figure-inline><figure-inline><figure-inline>[[File:Siren.gif|link=Pulmonary embolism resident survival guide|41x41px]]</figure-inline></figure-inline></figure-inline></figure-inline>|| <br> || <br>
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Pulmonary embolism}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Pulmonary_embolism]]
{{CMG}} {{ATI}}; {{AE}} {{Rim}}
{{CMG}} {{ATI}}; {{AE}} {{Rim}}


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==Differential Diagnosis==
==Differential Diagnosis==
===Differential Diagnosis Based on Symptoms===
===Differential Diagnosis Based on Symptoms===
Pulmonary embolism (PE) should be differentiated from other diseases presenting with [[chest pain]], [[shortness of breath]] and [[tachypnea]]. The differentials include the following:
Pulmonary embolism (PE) should be differentiated from other diseases presenting with [[chest pain]], [[shortness of breath]] and [[tachypnea]]. The differentials include the following:<ref name="pmid24550636">{{cite journal |vauthors=Brenes-Salazar JA |title=Westermark's and Palla's signs in acute and chronic pulmonary embolism: Still valid in the current computed tomography era |journal=J Emerg Trauma Shock |volume=7 |issue=1 |pages=57–8 |year=2014 |pmid=24550636 |pmc=3912657 |doi=10.4103/0974-2700.125645 |url=}}</ref><ref name="urlCT Angiography of Pulmonary Embolism: Diagnostic Criteria and Causes of Misdiagnosis | RadioGraphics">{{cite web |url=http://pubs.rsna.org/doi/full/10.1148/rg.245045008 |title=CT Angiography of Pulmonary Embolism: Diagnostic Criteria and Causes of Misdiagnosis &#124; RadioGraphics |format= |work= |accessdate=}}</ref><ref name="pmid23940438">{{cite journal |vauthors=Bĕlohlávek J, Dytrych V, Linhart A |title=Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism |journal=Exp Clin Cardiol |volume=18 |issue=2 |pages=129–38 |year=2013 |pmid=23940438 |pmc=3718593 |doi= |url=}}</ref><ref name="urlPulmonary Embolism: Symptoms - National Library of Medicine - PubMed Health">{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022657/ |title=Pulmonary Embolism: Symptoms - National Library of Medicine - PubMed Health |format= |work= |accessdate=}}</ref><ref name="pmid20118395">{{cite journal |vauthors=Ramani GV, Uber PA, Mehra MR |title=Chronic heart failure: contemporary diagnosis and management |journal=Mayo Clin. Proc. |volume=85 |issue=2 |pages=180–95 |year=2010 |pmid=20118395 |pmc=2813829 |doi=10.4065/mcp.2009.0494 |url=}}</ref><ref name="pmid18215495">{{cite journal |vauthors=Blinderman CD, Homel P, Billings JA, Portenoy RK, Tennstedt SL |title=Symptom distress and quality of life in patients with advanced congestive heart failure |journal=J Pain Symptom Manage |volume=35 |issue=6 |pages=594–603 |year=2008 |pmid=18215495 |pmc=2662445 |doi=10.1016/j.jpainsymman.2007.06.007 |url=}}</ref><ref name="pmid19168510">{{cite journal |vauthors=Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ |title=Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology |journal=Eur. J. Heart Fail. |volume=11 |issue=2 |pages=130–9 |year=2009 |pmid=19168510 |pmc=2639415 |doi=10.1093/eurjhf/hfn013 |url=}}</ref><ref name="pmid9465867">{{cite journal |vauthors=Takasugi JE, Godwin JD |title=Radiology of chronic obstructive pulmonary disease |journal=Radiol. Clin. North Am. |volume=36 |issue=1 |pages=29–55 |year=1998 |pmid=9465867 |doi= |url=}}</ref><ref name="pmid14651761">{{cite journal |vauthors=Wedzicha JA, Donaldson GC |title=Exacerbations of chronic obstructive pulmonary disease |journal=Respir Care |volume=48 |issue=12 |pages=1204–13; discussion 1213–5 |year=2003 |pmid=14651761 |doi= |url=}}</ref><ref name="pmid23833163">{{cite journal |vauthors=Nakawah MO, Hawkins C, Barbandi F |title=Asthma, chronic obstructive pulmonary disease (COPD), and the overlap syndrome |journal=J Am Board Fam Med |volume=26 |issue=4 |pages=470–7 |year=2013 |pmid=23833163 |doi=10.3122/jabfm.2013.04.120256 |url=}}</ref><ref name="pmid20511488">{{cite journal |vauthors=Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK |title=Pericardial disease: diagnosis and management |journal=Mayo Clin. Proc. |volume=85 |issue=6 |pages=572–93 |year=2010 |pmid=20511488 |pmc=2878263 |doi=10.4065/mcp.2010.0046 |url=}}</ref><ref name="pmid23610095">{{cite journal |vauthors=Bogaert J, Francone M |title=Pericardial disease: value of CT and MR imaging |journal=Radiology |volume=267 |issue=2 |pages=340–56 |year=2013 |pmid=23610095 |doi=10.1148/radiol.13121059 |url=}}</ref><ref name="pmid11680112">{{cite journal |vauthors=Gharib AM, Stern EJ |title=Radiology of pneumonia |journal=Med. Clin. North Am. |volume=85 |issue=6 |pages=1461–91, x |year=2001 |pmid=11680112 |doi= |url=}}</ref><ref name="pmid23507061">{{cite journal |vauthors=Schmidt WA |title=Imaging in vasculitis |journal=Best Pract Res Clin Rheumatol |volume=27 |issue=1 |pages=107–18 |year=2013 |pmid=23507061 |doi=10.1016/j.berh.2013.01.001 |url=}}</ref><ref name="pmid16891436">{{cite journal |vauthors=Suresh E |title=Diagnostic approach to patients with suspected vasculitis |journal=Postgrad Med J |volume=82 |issue=970 |pages=483–8 |year=2006 |pmid=16891436 |pmc=2585712 |doi=10.1136/pgmj.2005.042648 |url=}}</ref><ref name="pmid123074">{{cite journal |vauthors=Stein PD, Dalen JE, McIntyre KM, Sasahara AA, Wenger NK, Willis PW |title=The electrocardiogram in acute pulmonary embolism |journal=Prog Cardiovasc Dis |volume=17 |issue=4 |pages=247–57 |year=1975 |pmid=123074 |doi= |url=}}</ref><ref name="pmid23413894">{{cite journal |vauthors=Warnier MJ, Rutten FH, Numans ME, Kors JA, Tan HL, de Boer A, Hoes AW, De Bruin ML |title=Electrocardiographic characteristics of patients with chronic obstructive pulmonary disease |journal=COPD |volume=10 |issue=1 |pages=62–71 |year=2013 |pmid=23413894 |doi=10.3109/15412555.2012.727918 |url=}}</ref><ref name="pmid23000104">{{cite journal |vauthors=Stein PD, Matta F, Ekkah M, Saleh T, Janjua M, Patel YR, Khadra H |title=Electrocardiogram in pneumonia |journal=Am. J. Cardiol. |volume=110 |issue=12 |pages=1836–40 |year=2012 |pmid=23000104 |doi=10.1016/j.amjcard.2012.08.019 |url=}}</ref><ref name="pmid26209947">{{cite journal |vauthors=Hazebroek MR, Kemna MJ, Schalla S, Sanders-van Wijk S, Gerretsen SC, Dennert R, Merken J, Kuznetsova T, Staessen JA, Brunner-La Rocca HP, van Paassen P, Cohen Tervaert JW, Heymans S |title=Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis |journal=Int. J. Cardiol. |volume=199 |issue= |pages=170–9 |year=2015 |pmid=26209947 |doi=10.1016/j.ijcard.2015.06.087 |url=}}</ref><ref name="pmid20112390">{{cite journal |vauthors=Dennert RM, van Paassen P, Schalla S, Kuznetsova T, Alzand BS, Staessen JA, Velthuis S, Crijns HJ, Tervaert JW, Heymans S |title=Cardiac involvement in Churg-Strauss syndrome |journal=Arthritis Rheum. |volume=62 |issue=2 |pages=627–34 |year=2010 |pmid=20112390 |doi=10.1002/art.27263 |url=}}</ref>


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| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Vasculitis]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Vasculitis]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*On CT scan: (Takayasu arteritis)
*On [[Computed tomography|CT scan]]: ([[Takayasu's arteritis|Takayasu arteritis]])
**Vessel wall thickening
**[[Blood vessel|Vessel]] wall thickening
**Luminal narrowing of pulmonary artery
**Luminal narrowing of [[pulmonary artery]]
**Masses or nodules (ANCA-associated granulomatous vasculitis)
**Masses or nodules ([[Anti-neutrophil cytoplasmic antibody|ANCA]]-associated granulomatous vasculitis)
*On MRI:
*On [[Magnetic resonance imaging|MRI]]:
Homogeneous, circumferential vessel wall swelling  
Homogeneous, circumferential [[Blood vessel|vessel]] wall [[swelling]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Right or left bundle-branch block (Churg-Strauss syndrome)
*[[Bundle branch block|Right or left bundle-branch block]] ([[Churg-Strauss syndrome]])
*Atrial fibrillation (Churg-Strauss syndrome)
*[[Atrial fibrillation]] ([[Churg-Strauss syndrome]])
*Non-specific ST segment and T wave changes  
*Non-specific [[ST interval|ST segment]] and [[T wave]] changes  
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Nodules
*[[Nodule (medicine)|Nodules]]
*Cavitation
*[[Cavitation]]
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
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| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Takayasu arteritis usually found in persons aged 4-60 years with a mean of 30
*[[Takayasu's arteritis|Takayasu arteritis]] usually found in persons aged 4-60 years with a mean of 30
*Giant-cell arteritis usually occurrs in persons aged > 60 years
*[[Giant-cell arteritis]] usually occurrs in persons aged > 60 years
*Churg-Strauss syndrome may present with asthma, sinusitis, transient pulmonary infiltrates and neuropathy alongwith cardiac involvement
*[[Churg-Strauss syndrome]] may present with [[asthma]], [[sinusitis]], transient [[pulmonary]] infiltrates and neuropathy alongwith [[cardiac]] involvement
*Granulomatous vasculitides may present with nephtitis and upper airway (nasopharyngeal) destruction
*Granulomatous vasculitides may present with [[nephritis]] and [[upper airway]] ([[nasopharyngeal]]) destruction
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Chronic obstructive pulmonary disease]] (COPD)
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Chronic obstructive pulmonary disease]] (COPD)
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*On CT scan:
*On [[Computed tomography|CT scan]]:
**Chronic bronchitis may show bronchial wall thickening, scarring with bronchovascular irregularity, fibrosis
**[[Chronic bronchitis]] may show [[bronchial]] wall thickening, scarring with bronchovascular irregularity, [[fibrosis]]
**Emphysema may show alveolar septal destruction and airspace enlargement (Centrilobular- upper lobe, panlobular- lower lobe)
**[[Emphysema]] may show [[alveolar]] septal destruction and airspace enlargement (Centrilobular- upper lobe, panlobular- lower lobe)
**Giant bubbles
**Giant bubbles
*ON MRI:
*On [[MRI]]:
**Increased diameter of pulmonary arteries
**Increased diameter of [[pulmonary arteries]]
**Peripheral pulmonary vasculature attentuation
**Peripheral [[pulmonary]] [[vasculature]] attentuation
**Loss of retrosternal airspace due to right ventricular enlargement
**Loss of retrosternal airspace due to right ventricular enlargement
**Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung
**Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Multifocal atrial tachycardia (atleast 3 distinct P wave morphologies)
*[[Multifocal atrial tachycardia]] (atleast 3 distinct [[P waves|P wave]] morphologies)
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Enlarged lung shadows (emphysema)
*Enlarged [[lung]] shadows ([[emphysema]])
*Flattening of diaphragm (emphysema)
*Flattening of [[diaphragm]] ([[emphysema]])
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
| style="background: #F5F5F5; padding: 5px;" |✔
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| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Smoking
*[[Smoking]]
*Alpha-1 antitrypsin deficiency
*[[Alpha 1-antitrypsin deficiency|Alpha-1 antitrypsin deficiency]]
*Increased sputum production (chronic bronhitis)
*Increased [[sputum]] production ([[chronic bronchitis]])
*Cough
*[[Cough]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*Alpha 1 antitrypsin deficiency may be associated with hepatomegaly
*[[Alpha 1-antitrypsin deficiency|Alpha 1 antitrypsin deficiency]] may be associated with [[hepatomegaly]]
|}
|}



Latest revision as of 22:43, 19 February 2019

<figure-inline><figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline></figure-inline>

Resident
Survival
Guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] The APEX Trial Investigators; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Overview

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.

Differential Diagnosis

Differential Diagnosis Based on Symptoms

Pulmonary embolism (PE) should be differentiated from other diseases presenting with chest pain, shortness of breath and tachypnea. The differentials include the following:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]

Diseases Diagnostic tests Physical Examination Symptoms Past medical history Other Findings
CT scan and MRI EKG Chest X-ray Tachypnea Tachycardia Fever Chest Pain Hemoptysis Dyspnea on Exertion Wheezing Chest Tenderness Nasalopharyngeal Ulceration Carotid Bruit
Pulmonary embolism
  • On CT angiography:
    • Intra-luminal filling defect
  • On MRI:
    • Narrowing of involved vessel
    • No contrast seen distal to obstruction
    • Polo-mint sign (partial filling defect surrounded by contrast)
✔ (Low grade) ✔ (In case of massive PE) - - - -
Congestive heart failure
  • Goldberg's criteria may aid in diagnosis of left ventricular dysfunction: (High specificity)
    • SV1 or SV2 + RV5 or RV6 ≥3.5 mV
    • Total QRS amplitude in each of the limb leads ≤0.8 mV
    • R/S ratio <1 in lead V4
- - - - - -
Percarditis
  • ST elevation
  • PR depression
  • Large collection of fluid inside the pericardial sac (pericardial effusion)
  • Calcification of pericardial sac
✔ (Low grade) ✔ (Relieved by sitting up and leaning forward) - - - - -
  • May be clinically classified into:
    • Acute (< 6 weeks)
    • Sub-acute (6 weeks - 6 months)
    • Chronic (> 6 months)
Pneumonia - - - -
Vasculitis

Homogeneous, circumferential vessel wall swelling

-
Chronic obstructive pulmonary disease (COPD)
  • On CT scan:
  • On MRI:
    • Increased diameter of pulmonary arteries
    • Peripheral pulmonary vasculature attentuation
    • Loss of retrosternal airspace due to right ventricular enlargement
    • Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung
- - - - - -

Life Threatening Differential Diagnosis

Common Differential Diagnosis in Outpatients

Among outpatients presenting with dyspnea, <4 % are diagnosed with PE.[21] Common differential diagnoses include:[21]

Complete List of Differential Diagnosis

References

  1. Brenes-Salazar JA (2014). "Westermark's and Palla's signs in acute and chronic pulmonary embolism: Still valid in the current computed tomography era". J Emerg Trauma Shock. 7 (1): 57–8. doi:10.4103/0974-2700.125645. PMC 3912657. PMID 24550636.
  2. "CT Angiography of Pulmonary Embolism: Diagnostic Criteria and Causes of Misdiagnosis | RadioGraphics".
  3. Bĕlohlávek J, Dytrych V, Linhart A (2013). "Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism". Exp Clin Cardiol. 18 (2): 129–38. PMC 3718593. PMID 23940438.
  4. "Pulmonary Embolism: Symptoms - National Library of Medicine - PubMed Health".
  5. Ramani GV, Uber PA, Mehra MR (2010). "Chronic heart failure: contemporary diagnosis and management". Mayo Clin. Proc. 85 (2): 180–95. doi:10.4065/mcp.2009.0494. PMC 2813829. PMID 20118395.
  6. Blinderman CD, Homel P, Billings JA, Portenoy RK, Tennstedt SL (2008). "Symptom distress and quality of life in patients with advanced congestive heart failure". J Pain Symptom Manage. 35 (6): 594–603. doi:10.1016/j.jpainsymman.2007.06.007. PMC 2662445. PMID 18215495.
  7. Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ (2009). "Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology". Eur. J. Heart Fail. 11 (2): 130–9. doi:10.1093/eurjhf/hfn013. PMC 2639415. PMID 19168510.
  8. Takasugi JE, Godwin JD (1998). "Radiology of chronic obstructive pulmonary disease". Radiol. Clin. North Am. 36 (1): 29–55. PMID 9465867.
  9. Wedzicha JA, Donaldson GC (2003). "Exacerbations of chronic obstructive pulmonary disease". Respir Care. 48 (12): 1204–13, discussion 1213–5. PMID 14651761.
  10. Nakawah MO, Hawkins C, Barbandi F (2013). "Asthma, chronic obstructive pulmonary disease (COPD), and the overlap syndrome". J Am Board Fam Med. 26 (4): 470–7. doi:10.3122/jabfm.2013.04.120256. PMID 23833163.
  11. Khandaker MH, Espinosa RE, Nishimura RA, Sinak LJ, Hayes SN, Melduni RM, Oh JK (2010). "Pericardial disease: diagnosis and management". Mayo Clin. Proc. 85 (6): 572–93. doi:10.4065/mcp.2010.0046. PMC 2878263. PMID 20511488.
  12. Bogaert J, Francone M (2013). "Pericardial disease: value of CT and MR imaging". Radiology. 267 (2): 340–56. doi:10.1148/radiol.13121059. PMID 23610095.
  13. Gharib AM, Stern EJ (2001). "Radiology of pneumonia". Med. Clin. North Am. 85 (6): 1461–91, x. PMID 11680112.
  14. Schmidt WA (2013). "Imaging in vasculitis". Best Pract Res Clin Rheumatol. 27 (1): 107–18. doi:10.1016/j.berh.2013.01.001. PMID 23507061.
  15. Suresh E (2006). "Diagnostic approach to patients with suspected vasculitis". Postgrad Med J. 82 (970): 483–8. doi:10.1136/pgmj.2005.042648. PMC 2585712. PMID 16891436.
  16. Stein PD, Dalen JE, McIntyre KM, Sasahara AA, Wenger NK, Willis PW (1975). "The electrocardiogram in acute pulmonary embolism". Prog Cardiovasc Dis. 17 (4): 247–57. PMID 123074.
  17. Warnier MJ, Rutten FH, Numans ME, Kors JA, Tan HL, de Boer A, Hoes AW, De Bruin ML (2013). "Electrocardiographic characteristics of patients with chronic obstructive pulmonary disease". COPD. 10 (1): 62–71. doi:10.3109/15412555.2012.727918. PMID 23413894.
  18. Stein PD, Matta F, Ekkah M, Saleh T, Janjua M, Patel YR, Khadra H (2012). "Electrocardiogram in pneumonia". Am. J. Cardiol. 110 (12): 1836–40. doi:10.1016/j.amjcard.2012.08.019. PMID 23000104.
  19. Hazebroek MR, Kemna MJ, Schalla S, Sanders-van Wijk S, Gerretsen SC, Dennert R, Merken J, Kuznetsova T, Staessen JA, Brunner-La Rocca HP, van Paassen P, Cohen Tervaert JW, Heymans S (2015). "Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis". Int. J. Cardiol. 199: 170–9. doi:10.1016/j.ijcard.2015.06.087. PMID 26209947.
  20. Dennert RM, van Paassen P, Schalla S, Kuznetsova T, Alzand BS, Staessen JA, Velthuis S, Crijns HJ, Tervaert JW, Heymans S (2010). "Cardiac involvement in Churg-Strauss syndrome". Arthritis Rheum. 62 (2): 627–34. doi:10.1002/art.27263. PMID 20112390.
  21. 21.0 21.1 21.2 21.3 21.4 Squizzato A, Luciani D, Rubboli A, Di Gennaro L, Gennaro LD, Landolfi R; et al. (2013). "Differential diagnosis of pulmonary embolism in outpatients with non-specific cardiopulmonary symptoms". Intern Emerg Med. 8 (8): 695–702. doi:10.1007/s11739-011-0725-1. PMID 22094406.
  22. Restrepo CS, Artunduaga M, Carrillo JA, Rivera AL, Ojeda P, Martinez-Jimenez S; et al. (2009). "Silicone pulmonary embolism: report of 10 cases and review of the literature". J Comput Assist Tomogr. 33 (2): 233–7. doi:10.1097/RCT.0b013e31817ecb4e. PMID 19346851.

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