Pulmonary embolism D-dimer: Difference between revisions

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__NOTOC__
#Redirect [[D-dimer]]
{{Pulmonary embolism}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{CZ}}
 
==Overview==
[[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|congestive heart failure (CHF)]], [[Myocardial infarction|myocardial infarction (MI)]] and [[malignancy]]. [[False-negative]] values may occur in patients with prolonged symptoms of [[venous thromboembolism]] (≥14 days), patients on therapeutic [[heparin|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.<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><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>
== D-dimer ==
=== Abnormal Levels ===
[[D-dimer|Plasma D-dimer]] levels > 500 ng/mL are abnormal.<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>
 
=== Sensitivity and Specificity ===
 
====Sensitivity<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>====
[[ELISA]] ''(p=0.020)'', [[ELISA|quantitative rapid ELISA]] ''(p=0.016)'' and [[ELISA|semi-quantitative ELISA]] ''(p=0.047)'' are shown to be statistically superior to [[agglutination|whole-blood agglutination]].
 
====Specificity<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>====
[[ELISA|Qualitative rapid ELISA]] has shown to be statistically superior to [[ELISA]] ''(p=0.004)'', [[ELISA|quantitative rapid ELISA]] ''(p=0.002)'', [[ELISA|semi-quantitative rapid ELISA]] ''(p=0.001)'', [[latex agglutination test|quantitative]] ''(p=0.005)'' and [[latex agglutination test|semi-quantitative]] latex agglutination assays ''(p=0.019)''.
 
 
{| border="1"
|+
! Method !! Sensitivity (95% CI) !! Specificity (95% CI) !! Positive Likelihood Ratio (95% CI) !! Negative Likelihood Ratio (95% CI) !! Time to obtain Results
|-
| [[ELISA|Enzyme-linked immunosorbent assay (ELISA)]]
| align= "center" | 0.95 (0.85 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.13 (0.03 to 0.58)
| align= "center" | ≥ 8 hours
|-
| [[ELISA|Quantitative rapid ELISA]]
| align= "center" | 0.95 (0.83 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.13 (0.02 to 0.84)
| align= "center" | 30 mins
|-
| [[ELISA|Semi-Quantitative rapid ELISA]]
| align= "center" | 0.93 (0.79 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.20 (0.04 to 0.96)
| align= "center" | 10 mins
|-
| [[ELISA|Qualitative rapid ELISA]]
| align= "center" | NS
| align= "center" | 0.68 (0.50 to 0.87)
| align= "center" | NS
| align= "center" | 0.11 (0.01 to 0.93)
| align= "center" | 10 mins
|-
| [[Latex agglutination test|Quantitative Latex Agglutination]]
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | 10-15 mins
|-
| [[Latex agglutination test|Semi-quantitative Latex Agglutination]]
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.17 (0.04 to 0.78)
| align= "center" | 5 mins
|-
| [[Latex agglutination test|Whole-Blood Agglutination]]
| align= "center" | NS
| align= "center" | 0.74 (0.60 to 0.88)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 2 mins
|}
 
=== Hemodynamically Stable Patients ===
====Incidence of Thromboembolic Events in Hemodynamically Stable Patients====
{| border="1"
|+
! Condition !! Incidence of thromboembolic event (%)
|-
| Patients not receiving anticoagulation with negative CT findings.
| 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>
|-
| Patients with a high d-dimer level
| 1.5%
|-
| Patients with a normal d-dimer level
| 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>
|}
 
*[[Pulmonary embolism CT#Multi-Detector CT|Multidetector CT]] is indicated in hemodynamically stable patients with a high clinical probability of PE and/or patients with elevated plasma [[d-dimer]] levels secondary to the lack of specificity.<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><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>
 
*In patients with low-to-moderate suspicion of PE, a normal [[D-dimer]] level is considered sufficient to exclude the possibility of pulmonary embolism.<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>
 
=== Flowchart Summarizing the Role of D-dimer in the Diagnosis of PE ===
{{familytree/start |summary=Use of D-Dimer.}}
{{familytree | | | | GMa | GMa=Patients with suspection of [[Pulmonary embolism]]}}
{{familytree | |,|-|-|^|-|-|-|.| | | }}
{{familytree |JOE| | | | |SIS| | | JOE=Clinically Low or Moderate|SIS=Clinically High}}
{{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}}
 
 
A new D-Dimer (DDMR) analyzer has shown to be more accurate in excluding patients with a low 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>
 
==ESC 2008 Guideline Recommendations <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"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| 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"
|-
| 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 either a highly or moderately sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
 
|}
 
====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>
 
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIa]]
|-
|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>
 
|}
 
====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>====
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
|-
|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>
 
|}
 
==References==
{{reflist|2}}
 
[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Intensive care medicine]]
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Latest revision as of 13:52, 9 September 2013

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