Pulmonary embolism laboratory findings: Difference between revisions

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__NOTOC__
{| 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''']]
|}
{{Pulmonary embolism}}
{{Pulmonary embolism}}
{{PE editors}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{Rim}}


==Overview==
==Overview==
Routine laboratory tests including [[ABG|arterial blood gas]] analysis are non-specific in patients with acute pulmonary embolism; however, in cases of suspected PE they may be ordered to rule-out secondary causes.  
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==
===D-dimer Test===
''Fore more information about [[D-dimer]], click '''[[D-dimer|here]]'''.''


==Laboratory tests==
* [[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]].
*In patients with '''''acute''''' pulmonary embolism, routine laboratory findings are '''''non-specific''''' and include: [[leukocytosis]], [[erythrocyte sedimentation rate|elevated ESR]] with an elevated [[LDH|serum LDH]] and [[transaminases|serum transaminase]] (especially [[Aspartate transaminase|AST or SGOT]]). However, [[bilirubin|serum bilirubin]] levels are found to be within normal limits.


*In patients with '''''suspected''''' pulmonary embolism, routine laboratory tests are ordered to '''''exclude the secondary causes''''' of PE. These tests include:
* [[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>
:*[[Complete blood count]],
:*[[Erythrocyte sedimentation rate]],
:*[[Coagulation studies]],
:*Other screening tests such as [[renal function tests]], [[LFT|liver function tests]] and [[electrolyte|electrolyte]] assessment.  


==Arterial blood gas (ABG)==
* [[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>
*In patients with pulmonary embolism, [[ABG|arterial blood gas]] analysis may reveal:<ref name="pmid2491801">{{cite journal |author=Cvitanic O, Marino PL |title=Improved use of arterial blood gas analysis in suspected pulmonary embolism |journal=[[Chest]] |volume=95 |issue=1 |pages=48–51 |year=1989 |month=January |pmid=2491801 |doi= |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2491801 |accessdate=2012-04-30}}</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>
:*[[Hypoxemia]],
**Plasma [[D-dimer]]<500 excludes [[PE]] (high [[negative predictive value]])
:*[[Hypocapnia]],
:*Increased [[alveolar-arterial oxygen difference]] ([[Alveolar-arterial gradient|P(A-a)O2 gradient]]) and
:*[[Respiratory alkalosis]].


*However, the above mentioned [[ABG]] findings are not exclusive for the diagnosis PE. Some variations include:
* 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:
:*[[Hypercapnia]] in cases of massive PE secondary to circulatory collapse.
** If age <50 years, the cut off value for [[D-dimer]] is 500 ng/mL.
:*Normal [[PaO2]] ''(partial pressure of oxygen in arterial blood)'' levels as demonstrated by majority of patients.<ref name="pmid1909617">{{cite journal |author=Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT, Weg JG |title=Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease |journal=[[Chest]] |volume=100 |issue=3 |pages=598–603 |year=1991 |month=September |pmid=1909617 |doi= |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=1909617 |accessdate=2012-04-30}}</ref>  
** 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>
:*Normal [[alveolar-arterial oxygen gradient]] may be observed in ~6% of patients.


=====Sensitivity and Specificity=====
===Routine Blood Tests===
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.<ref name="pmid11112122">{{cite journal |author=Rodger MA, Carrier M, Jones GN, Rasuli P, Raymond F, Djunaedi H, Wells PS |title=Diagnostic value of arterial blood gas measurement in suspected pulmonary embolism |journal=[[American Journal of Respiratory and Critical Care Medicine]] |volume=162 |issue=6 |pages=2105–8 |year=2000 |month=December |pmid=11112122 |doi= |url=http://ajrccm.atsjournals.org/cgi/pmidlookup?view=long&pmid=11112122 |accessdate=2012-04-30}}</ref> Similar findings were observed by the PIOPED II investigators.<ref name="pmid17145249">{{cite journal |author=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 |title=Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators |journal=[[The American Journal of Medicine]] |volume=119 |issue=12 |pages=1048–55 |year=2006 |month=December |pmid=17145249 |doi=10.1016/j.amjmed.2006.05.060 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(06)00779-0 |accessdate=2012-04-30}}</ref>
*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>
:*[[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>
:*Elevated [[LDH|serum LDH]]<ref name="pmid8351437">{{cite journal| author=Hasegawa K, Sawayama T, Ibukiyama C, Muramatsu J, Ozawa Y, Kanemoto N et al.| title=[Early diagnosis and management of acute pulmonary embolism: clinical evaluation those of 225 cases]. | journal=Kokyu To Junkan | year= 1993 | volume= 41 | issue= 8 | pages= 773-7 | pmid=8351437 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8351437  }} </ref>
:* Elevated [[transaminases|serum transaminase]] (especially [[Aspartate transaminase|AST or SGOT]])<ref name="pmid18971188">{{cite journal| author=Hu ZJ, Zhou YQ, Zhang HB, Li L| title=[Clinical value of monitoring serum cardiac biomarkers in pulmonary thromboembolism-induced myocardial injury]. | journal=Nan Fang Yi Ke Da Xue Xue Bao | year= 2008 | volume= 28 | issue= 10 | pages= 1853-5 | pmid=18971188 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18971188  }} </ref>


==D-dimers==
===Workup for Hypercoagulability===
This is formed by the degradation of fibrin clot. Almost all patients with PE have some endogenous fibrinolysis, and therefore have elevated levels of D-dimer.
*Workup for [[hypercoagulation]] includes:
* The negative predictive value (when done by ELISA) is 91% – 94% .
**Activated [[protein C]] resistance
* Many other diseases are associated with a mild degree of fibrinolysis, and hence an elevated D-dimer is not specific for pulmonary embolism. Disease with elevated levels of D-dimer are:
**[[Factor V Leiden]] [[mutation]]
**[[Pneumonia]]  
**[[Protein C]]
**[[Congestive heart failure|Congestive heart failure (CHF)]]  
**[[Protein S]] (free and total)
**[[Myocardial infarction|Myocardial infarction (MI)]]
**[[Antithrombin]]
**[[Malignancy]]  
**[[Lupus anticoagulant]]
**[[Anticardiolipin antibodies]]
**Plasma [[homocysteine]] values


D-Dimer levels are elevated in other medical conditions such as:
* 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>
# Pregnancy
# After surgery
# Hospitalized patient.<ref name="pmid19712840">{{cite journal| author=Bruinstroop E, van de Ree MA, Huisman MV| title=The use of D-dimer in specific clinical conditions: a narrative review. | journal=Eur J Intern Med | year= 2009 | volume= 20 | issue= 5 | pages= 441-6 | pmid=19712840 | doi=10.1016/j.ejim.2008.12.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19712840  }} </ref> Thus, most hospitalized patients should not undergo D-dimer testing if PE is suspected.<ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294 }} </ref>


Patients who are '''hemodynamically stable''', but have a high clinical probability or those having a high d-dimer level should undergo [[Computed tomography#Multislice CT|multidetector CT]].<ref name="pmid16403929">{{cite journal| author=van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW et al.| title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. | journal=JAMA | year= 2006 | volume= 295 | issue= 2 | pages= 172-9 | pmid=16403929 | doi=10.1001/jama.295.2.172 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403929 }} </ref> The following table depicts the incidences of thromboembolic events in hemodynamicaly stable patients.
* 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>
{| border="1"
** Upper limb [[thrombosis]]
|+
** Central [[venous]] catheter related [[thrombosis]]
! Condition !! Incidence of thromboembolic event (%)
** Retinal [[vein]] occlusion
** Recent major surgery
** Recent [[trauma]]
** Recent immobilization
** Active [[cancer]]
 
==The 2008 Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>==
 
===Suspected Non High-risk PE Patients (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>===
{|class="wikitable"
|-
|-
| Patients not receiving anticoagulation and with negative CT findings.
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
| 1.5%<ref name="pmid15858185">{{cite journal| author=Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL et al.|title=Multidetector-row computed tomography in suspected pulmonary embolism. | journal=N Engl J Med | year= 2005 | volume= 352|issue= 17 | pages= 1760-8 | pmid=15858185 | doi=10.1056/NEJMoa042905 | pmc=|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15858185}}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16118905Review in: J Fam Pract. 2005 Aug;54(8):653, 657] </ref><ref name="pmid16403929">{{cite journal| author=van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW et al.|title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. | journal=JAMA | year= 2006 | volume= 295 |issue= 2 | pages= 172-9 | pmid=16403929 | doi=10.1001/jama.295.2.172| pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403929 }} </ref>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''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. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}
 
====Low Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
{|class="wikitable"
|-
|-
| Patients with High d-dimer level
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
| 1.5%
|-
|-
| Patients with Normal d-dimer level
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Normal D-dimer level using either a highly or moderately sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
| 0.5%<ref name="pmid15858185">{{cite journal| author=Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL et al.|title=Multidetector-row computed tomography in suspected pulmonary embolism. | journal=N Engl J Med | year= 2005 | volume= 352|issue= 17 | pages= 1760-8 | pmid=15858185 | doi=10.1056/NEJMoa042905 | pmc=|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15858185}}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16118905Review in: J Fam Pract. 2005 Aug;54(8):653, 657] </ref>
|}
|}


In '''low-to-moderate''' suspicion of PE, a normal [[D-dimer]] level (shown in a [[blood test]]) is enough to exclude the possibility of thrombotic PE.<ref name="pmid8165626">{{cite journal |author=Bounameaux H, de Moerloose P, Perrier A, Reber G|title=Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview |journal=Thromb. Haemost.|volume=71 |issue=1 |pages=1-6 |year=1994 |pmid=8165626 |doi=}}</ref> In patients with '''High''' clinical probability, the use of the d-dimer assay is of limited value.<ref name="pmid19620439">{{cite journal| author=Gupta RT, Kakarla RK, Kirshenbaum KJ, Tapson VF| title=D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism. |journal=AJR Am J Roentgenol | year= 2009 | volume= 193 | issue= 2 | pages= 425-30 | pmid=19620439 |doi=10.2214/AJR.08.2186 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19620439 }} </ref>
====Intermediate Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Normal D-dimer level using a highly sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}


'''The following flowchart summarize the role of D-dimer''':
{|class="wikitable"
{{familytree/start |summary=Use of D-Dimer.}}
|-
{{familytree | | | | GMa | GMa=Patients with suspection of [[Pulmonary embolism]]}}
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIa]]
{{familytree | |,|-|-|^|-|-|-|.| | | }}
|-
{{familytree |JOE| | | | |SIS| | | JOE=Clinically Low or Moderate|SIS=Clinically High}}
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Further testing should be considered if D-dimer level is normal when using a less sensitive assay. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
{{familytree |,|^|-|.| | | | |!| }}
|}
{{familytree |!| | |!| | | | |!| }}
{{familytree |!| | |ME| | |!|ME=D-Dimer Positive}}
{{familytree |!| | | |!| | | |!| }}
{{familytree |MOM| |!| | | |!| |MOM=D-Dimer Negative|}}
{{familytree | |!| | |!| | | |!| }}
{{familytree |GPa| |ME| |SIS|GPa=No treatment|ME=Further Tests|SIS=Further Tests}}
{{familytree/end}}


 
====High Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=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 |title=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) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
A new D-Dimer (DDMR) analyzer has shown to have higher accuracy in excluding patients with non-high clinical pre-test probability.<ref name="pmid22245223">{{cite journal| author=Gosselin RC, Wu JR, Kottke-Marchant K, Peetz D, Christie DJ, Muth H et al.| title=Evaluation of the Stratus® CS Acute Care™ D-dimer assay (DDMR) using the Stratus® CS STAT Fluorometric Analyzer: A prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis. | journal=Thromb Res | year= 2012 | volume=  | issue=  | pages=  | pmid=22245223 | doi=10.1016/j.thromres.2011.12.015 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22245223  }} </ref>
{|class="wikitable"
 
|-
==Brain natriuretic peptide (BNP)==
|colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
In a case-control study of 2213 hemodynamically stable patients with suspected acute PE, BNP was found to have 60% sensitivity and 62% specificity.<ref name="pmid16405522">{{cite journal| author=Söhne M, Ten Wolde M, Boomsma F, Reitsma JB, Douketis JD, Büller HR| title=Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. | journal=J Thromb Haemost | year= 2006 | volume= 4 | issue= 3 | pages= 552-6 | pmid=16405522 | doi=10.1111/j.1538-7836.2005.01752.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16405522  }} </ref>
|-
 
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''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. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
BNP levels are typically higher in PE patients as compared to patients without PE; however, certain features limit its usefulness as a diagnostic test:
|}
*Many patients with PE do not have elevated BNP levels.
*There are many alternative causes of an elevated BNP level (proving it to be nonspecific).<ref name="pmid16099151">{{cite journal| author=Kiely DG, Kennedy NS, Pirzada O, Batchelor SA, Struthers AD, Lipworth BJ| title=Elevated levels of natriuretic peptides in patients with pulmonary thromboembolism. | journal=Respir Med | year= 2005 | volume= 99 | issue= 10 | pages= 1286-91 | pmid=16099151 | doi=10.1016/j.rmed.2005.02.029 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16099151  }} </ref>
 
In hemodynamically stable patients, normal level of BNP and pro-BNP have 100% negative predictive value (NPV) for an adverse outcome.<ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294  }} </ref> High level of BNP distinguish patients with pulmonary embolism at higher risk of complicated in-hospital duration and death, when compared with those with low BNP levels. However an isolated increase in BNP or NT-pro-BNP level, do not justify more invasive treatment regimens.<ref name="pmid18556626">{{cite journal| author=Klok FA, Mos IC, Huisman MV| title=Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. | journal=Am J Respir Crit Care Med | year= 2008 | volume= 178 | issue= 4 | pages= 425-30 | pmid=18556626 | doi=10.1164/rccm.200803-459OC | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18556626  }} </ref>
 
==Troponin==
Serum troponin I and troponin T are elevated in approximately thirty to fifty percent of the PE patients.<ref name="pmid12904706">{{cite journal| author=Horlander KT, Leeper KV| title=Troponin levels as a guide to treatment of pulmonary embolism. | journal=Curr Opin Pulm Med | year= 2003 | volume= 9 | issue= 5 | pages= 374-7 | pmid=12904706 | doi= | pmc= | url= }} </ref><ref name="pmid12208803">{{cite journal| author=Konstantinides S, Geibel A, Olschewski M, Kasper W, Hruska N, Jäckle S et al.| title=Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism. | journal=Circulation | year= 2002 | volume= 106 | issue= 10 | pages= 1263-8 | pmid=12208803 | doi= | pmc= | url= }} </ref> The suspected mechanism is due to acute right heart overload.<ref name="pmid11079669">{{cite journal| author=Meyer T, Binder L, Hruska N, Luthe H, Buchwald AB| title=Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 5 | pages= 1632-6 | pmid=11079669 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11079669  }} </ref> Troponin elevation is more prolonged in acute MI rather in PE and usually resolve within 40 hours after a PE event.<ref name="pmid11901075">{{cite journal| author=Müller-Bardorff M, Weidtmann B, Giannitsis E, Kurowski V, Katus HA| title=Release kinetics of cardiac troponin T in survivors of confirmed severe pulmonary embolism. | journal=Clin Chem | year= 2002 | volume= 48 | issue= 4 | pages= 673-5 | pmid=11901075 | doi= | pmc= | url= }} </ref> Thus troponins are not useful for diagnosis, but there role in prognostic assessment has been proved in a meta-analysis.<ref name="pmid18094010">{{cite journal| author=Jiménez D, Díaz G, Molina J, Martí D, Del Rey J, García-Rull S et al.| title=Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism. | journal=Eur Respir J | year= 2008 | volume= 31 | issue= 4 | pages= 847-53 | pmid=18094010 | doi=10.1183/09031936.00113307 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18094010  }} </ref>


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

Pulmonary Embolism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Pulmonary Embolism from other Diseases

Epidemiology and Demographics

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Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

Assessment of Clinical Probability and Risk Scores

Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Arterial Blood Gas Analysis

D-dimer

Biomarkers

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Ventilation/Perfusion Scan

Echocardiography

Compression Ultrasonography

CT

MRI

Treatment

Treatment approach

Medical Therapy

IVC Filter

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Case #1

Pulmonary embolism laboratory findings On the Web

Most recent articles

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Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Pulmonary embolism laboratory findings

CDC on Pulmonary embolism laboratory findings

Pulmonary embolism laboratory findings in the news

Blogs on Pulmonary embolism laboratory findings

Directions to Hospitals Treating Pulmonary embolism laboratory findings

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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