Pulmonary embolism laboratory findings: Difference between revisions

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__NOTOC__
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{| class="infobox" style="float:right;"
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| [[File:Siren.gif|30px|link=Pulmonary embolism resident survival guide]]|| <br> || <br>
| [[Pulmonary embolism resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Pulmonary embolism}}
{{Pulmonary embolism}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{Rim}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{Rim}}


==Overview==
==Overview==
The results of routine laboratory tests including [[ABG|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]], [[erythrocyte sedimentation rate|elevated ESR]] with an elevated [[LDH|serum LDH]] and [[transaminases|serum transaminase]] (especially [[Aspartate transaminase|AST or SGOT]]).  A negative [[D-dimer]] in a patient with low to intermediate probability of pulmonary embolism strongly suggests pulmonary embolism is not present.
The results of routine laboratory tests including [[ABG|arterial blood gas]] analysis are non-specific in making the diagnosis of pulmonary embolism (PE).  These laboratory studies can be obtained to rule out other cause of [[chest discomfort]] and [[tachypnea]].  In patients with [[acute]] [[PE]], non-specific lab findings include: [[leukocytosis]], [[erythrocyte sedimentation rate|elevated ESR]] with an elevated [[LDH|serum LDH]] and [[transaminases|serum transaminase]] (especially [[Aspartate transaminase|AST or SGOT]]).  A negative [[D-dimer]] in a patient with low to intermediate probability of [[PE]] strongly suggests [[PE]] is not present.


==Laboratory Findings==
==Laboratory Findings==
===D-dimer Test===
===D-dimer Test===
''Fore more information about D-dimer, click '''[[D-dimer|here]]'''.''
''Fore more information about [[D-dimer]], click '''[[D-dimer|here]]'''.''


* The D-dimer cut-off values varies among tests; however, [[D-dimer|plasma D-dimer]] > 500 ng/mL is the most commonly used cut-off concentration.<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=[[Annals of Internal Medicine]] |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |accessdate=2012-05-07}}</ref>
* [[D-dimer]] is a cross-linked [[fibrin degradation product]] and a marker of [[endogenous]] [[fibrinolysis]]. In the setting of ongoing [[thrombosis]], D-dimer's concentration is elevated in the blood and thus makes it a screening tool to rule out [[DVT]].
**Plasma D-dimer>500 ng/ml, PE present (sensitivity: 84.8%; specificity:68.4%)<ref name="pmid9867754">{{cite journal| author=Ginsberg JS, Wells PS, Kearon C, Anderson D, Crowther M, Weitz JI et al.| title=Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 12 | pages= 1006-11 | pmid=9867754 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9867754  }} </ref>
**Plasma D-dimer<500 excludes PE (high negative predictive value)


* However, the use of the cut off value 500 ng/mL for abnormal D-dimer limits the diagnostic role of D-dimer in the elderly, among whom D-dimer increases with age in the absence of any ongoing [[venous thromboembolism]] process.  The age adjusted cut off value of D-dimer is the following:
* [[D-dimer]] is the test of choice in patients who are considered to be at low or intermediate risk of [[PE]] according to [[Wells score for DVT|pre-test probability]].  [[D-dimer]] is more useful if its negative rather than positive. It has a great '''[[negative predictive value]]''' in low to moderate risk patients.  If [[D-dimer]] is elevated, then [[DVT]] should be confirmed with [[Deep vein thrombosis ultrasound|ultrasound]].<ref name="pmid14507948">{{cite journal |author=Wells PS, Anderson DR, Rodger M, ''et al'' |title=Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis |journal=N. Engl. J. Med. |volume=349 |issue=13 |pages=1227-35 |year=2003 |pmid=14507948 |doi=10.1056/NEJMoa023153}}</ref><ref name="pmid12755550">{{cite journal |author=Bates SM, Kearon C, Crowther M, ''et al'' |title=A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis |journal=Ann. Intern. Med. |volume=138 |issue=10 |pages=787-94 |year=2003 |pmid=12755550 |doi=}}</ref>
** If age <50 years, the cut off value for D-dimer is 500 ng/mL.
 
** If age >50 years, the cut off value for D-dimer is age multiplied by 10.<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><ref name="pmid23645857">{{cite journal| author=Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA et al.| title=Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. | journal=BMJ | year= 2013 | volume= 346 | issue=  | pages= f2492 | pmid=23645857 | doi=10.1136/bmj.f2492 | pmc=PMC3643284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23645857  }} </ref><ref name="JAMA 2014"> Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135. </ref>
* [[D-dimer|Plasma D-dimer]] > 500 ng/mL is the most commonly used cut-off concentration.<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=[[Annals of Internal Medicine]] |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |accessdate=2012-05-07}}</ref>
**Plasma [[D-dimer]]>500 ng/ml, PE present ([[sensitivity]]: 84.8%; [[specificity]]:68.4%)<ref name="pmid9867754">{{cite journal| author=Ginsberg JS, Wells PS, Kearon C, Anderson D, Crowther M, Weitz JI et al.| title=Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 12 | pages= 1006-11 | pmid=9867754 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9867754  }} </ref>
**Plasma [[D-dimer]]<500 excludes [[PE]] (high [[negative predictive value]])
 
* However, the use of the cut off value 500 ng/mL for abnormal [[D-dimer]] limits the diagnostic role of [[D-dimer]] in the elderly, among whom [[D-dimer]] increases with age in the absence of any ongoing [[venous thromboembolism]] (VTE) process.  The age adjusted cut off value of [[D-dimer]] is the following:
** If age <50 years, the cut off value for [[D-dimer]] is 500 ng/mL.
** If age >50 years, the cut off value for [[D-dimer]] is age multiplied by 10.<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><ref name="pmid23645857">{{cite journal| author=Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA et al.| title=Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. | journal=BMJ | year= 2013 | volume= 346 | issue=  | pages= f2492 | pmid=23645857 | doi=10.1136/bmj.f2492 | pmc=PMC3643284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23645857  }} </ref><ref name="JAMA 2014"> Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135. </ref>


===Routine Blood Tests===
===Routine Blood Tests===
*In patients with acute pulmonary embolism, routine laboratory findings are non-specific and include:
*In patients with [[acute]] [[PE]], routine laboratory findings are non-specific and include:
:*[[Leukocytosis]]<ref name="pmid10334148">{{cite journal| author=Afzal A, Noor HA, Gill SA, Brawner C, Stein PD| title=Leukocytosis in acute pulmonary embolism. | journal=Chest | year= 1999 | volume= 115 | issue= 5 | pages= 1329-32 | pmid=10334148 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10334148  }} </ref>
:*[[Leukocytosis]]<ref name="pmid10334148">{{cite journal| author=Afzal A, Noor HA, Gill SA, Brawner C, Stein PD| title=Leukocytosis in acute pulmonary embolism. | journal=Chest | year= 1999 | volume= 115 | issue= 5 | pages= 1329-32 | pmid=10334148 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10334148  }} </ref>
:*[[erythrocyte sedimentation rate|Elevated ESR]]<ref name="pmid15970718">{{cite journal| author=Kokturk N, Demir N, Oguzulgen IK, Demirel K, Ekim N| title=Fever in pulmonary embolism. | journal=Blood Coagul Fibrinolysis | year= 2005 | volume= 16 | issue= 5 | pages= 341-7 | pmid=15970718 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15970718  }} </ref>
:*[[erythrocyte sedimentation rate|Elevated ESR]]<ref name="pmid15970718">{{cite journal| author=Kokturk N, Demir N, Oguzulgen IK, Demirel K, Ekim N| title=Fever in pulmonary embolism. | journal=Blood Coagul Fibrinolysis | year= 2005 | volume= 16 | issue= 5 | pages= 341-7 | pmid=15970718 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15970718  }} </ref>
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*Workup for [[hypercoagulation]] includes:
*Workup for [[hypercoagulation]] includes:
**Activated [[protein C]] resistance  
**Activated [[protein C]] resistance  
**[[Factor V]] Leiden mutation
**[[Factor V Leiden]] [[mutation]]
**[[Protein C]]
**[[Protein C]]
**[[Protein S]] (free and total)
**[[Protein S]] (free and total)
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**Plasma [[homocysteine]] values
**Plasma [[homocysteine]] values


* The hypercoagulability tests are not part of the routine workup for all patients who suffer from PE.  The hypercoagulability workup should be considered in the case of unprovoked venous thrombosis at an early age (< 40 years), strong family history of more than 2 relative who had VTE symptoms, and pregnant women who had a previous VTE episode in the absence of a significant trigger.<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>
* The [[hypercoagulability]] tests are not part of the routine workup for all patients who suffer from [[PE]].  The [[hypercoagulability]] workup should be considered in the case of unprovoked [[venous]] [[thrombosis]] at an early age (< 40 years), strong family history of more than 2 relatives who had [[VTE]] symptoms, and pregnant women who had a previous [[VTE]] episode in the absence of a significant trigger.<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>


* The hypercoagulability workup should not be performed in the cases of:<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>
* The [[hypercoagulability]] workup should not be performed in the cases of:<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>
** Upper limb thrombosis
** Upper limb [[thrombosis]]
* Central venous catheter related thrombosis
** Central [[venous]] catheter related [[thrombosis]]
** Retinal vein occlusion
** Retinal [[vein]] occlusion
** Recent major surgery
** Recent major surgery
** Recent [[trauma]]
** Recent [[trauma]]
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==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


[[Category:Hematology]]
[[Category:Hematology]]
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[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]
[[Category:Intensive care medicine]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Latest revision as of 23:53, 29 July 2020
Resident
Survival
Guide

Pulmonary Embolism Microchapters

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Risk calculators and risk factors for Pulmonary embolism laboratory findings

Editor(s)-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

The results of routine laboratory tests including arterial blood gas analysis are non-specific in making the diagnosis of pulmonary embolism (PE). These laboratory studies can be obtained to rule out other cause of chest discomfort and tachypnea. In patients with acute PE, non-specific lab findings include: leukocytosis, elevated ESR with an elevated serum LDH and serum transaminase (especially AST or SGOT). A negative D-dimer in a patient with low to intermediate probability of PE strongly suggests PE is not present.

Laboratory Findings

D-dimer Test

Fore more information about D-dimer, click here.

  • However, the use of the cut off value 500 ng/mL for abnormal D-dimer limits the diagnostic role of D-dimer in the elderly, among whom D-dimer increases with age in the absence of any ongoing venous thromboembolism (VTE) process. The age adjusted cut off value of D-dimer is the following:
    • If age <50 years, the cut off value for D-dimer is 500 ng/mL.
    • If age >50 years, the cut off value for D-dimer is age multiplied by 10.[5][6][7]

Routine Blood Tests

  • In patients with acute PE, routine laboratory findings are non-specific and include:

Workup for Hypercoagulability

  • The hypercoagulability tests are not part of the routine workup for all patients who suffer from PE. The hypercoagulability workup should be considered in the case of unprovoked venous thrombosis at an early age (< 40 years), strong family history of more than 2 relatives who had VTE symptoms, and pregnant women who had a previous VTE episode in the absence of a significant trigger.[12]

The 2008 Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)[13]

Suspected Non High-risk PE Patients (DO NOT EDIT)[13]

Class I
"1. Plasma D-dimer measurement is recommended in emergency department patients to reduce the need for unnecessary imaging and irradiation, preferably with the use of a highly sensitive assay. (Level of Evidence: A) "

Low Clinical Probability (DO NOT EDIT)[13]

Class I
"1. Normal D-dimer level using either a highly or moderately sensitive assay excludes pulmonary embolism. (Level of Evidence: A) "

Intermediate Clinical Probability (DO NOT EDIT)[13]

Class I
"1. Normal D-dimer level using a highly sensitive assay excludes pulmonary embolism. (Level of Evidence: A) "
Class IIa
"1. Further testing should be considered if D-dimer level is normal when using a less sensitive assay. (Level of Evidence: B) "

High Clinical Probability (DO NOT EDIT)[13]

Class III
"1. D-dimer measurement is not recommended in high clinical probability patients as a normal result does not safely exclude pulmonary embolism even when using a highly sensitive assay. (Level of Evidence: C) "

References

  1. ↑ Wells PS, Anderson DR, Rodger M; et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N. Engl. J. Med. 349 (13): 1227–35. doi:10.1056/NEJMoa023153. PMID 14507948.
  2. ↑ Bates SM, Kearon C, Crowther M; et al. (2003). "A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis". Ann. Intern. Med. 138 (10): 787–94. PMID 12755550.
  3. ↑ Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK (2004). "D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review". Annals of Internal Medicine. 140 (8): 589–602. PMID 15096330. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  4. ↑ Ginsberg JS, Wells PS, Kearon C, Anderson D, Crowther M, Weitz JI; et al. (1998). "Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism". Ann Intern Med. 129 (12): 1006–11. PMID 9867754.
  5. ↑ Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C; et al. (2012). "Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded". Haematologica. 97 (10): 1507–13. doi:10.3324/haematol.2011.060657. PMC 3487551. PMID 22511491.
  6. ↑ Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA; et al. (2013). "Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis". BMJ. 346: f2492. doi:10.1136/bmj.f2492. PMC 3643284. PMID 23645857.
  7. ↑ Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135.
  8. ↑ Afzal A, Noor HA, Gill SA, Brawner C, Stein PD (1999). "Leukocytosis in acute pulmonary embolism". Chest. 115 (5): 1329–32. PMID 10334148.
  9. ↑ Kokturk N, Demir N, Oguzulgen IK, Demirel K, Ekim N (2005). "Fever in pulmonary embolism". Blood Coagul Fibrinolysis. 16 (5): 341–7. PMID 15970718.
  10. ↑ Hasegawa K, Sawayama T, Ibukiyama C, Muramatsu J, Ozawa Y, Kanemoto N; et al. (1993). "[Early diagnosis and management of acute pulmonary embolism: clinical evaluation those of 225 cases]". Kokyu To Junkan. 41 (8): 773–7. PMID 8351437.
  11. ↑ Hu ZJ, Zhou YQ, Zhang HB, Li L (2008). "[Clinical value of monitoring serum cardiac biomarkers in pulmonary thromboembolism-induced myocardial injury]". Nan Fang Yi Ke Da Xue Xue Bao. 28 (10): 1853–5. PMID 18971188.
  12. ↑ 12.0 12.1 Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S; et al. (2010). "Clinical guidelines for testing for heritable thrombophilia". Br J Haematol. 149 (2): 209–20. doi:10.1111/j.1365-2141.2009.08022.x. PMID 20128794.
  13. ↑ 13.0 13.1 13.2 13.3 13.4 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP (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. Retrieved 2011-12-07. Unknown parameter |month= ignored (help)

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