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| {{Pulmonary embolism}}
| | #Redirect [[D-dimer]] |
| {{PE editors}}
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| ==Overview==
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| [[D-dimer]] is a [[fibrin degradation product]], that is elevated in the plasma after an acute blood clot. Majority of the patients with pulmonary embolism have some degree of endogenous [[fibrinolysis]] with subsequent elevation of [[D-dimer]]. Therefore, the [[negative predictive value]] of D-dimer for the diagnosis of pulmonary embolism is very high. Despite this specificity, a wide range of diseases associated with mild degree of [[fibrinolysis]] may falsely elevate [[D-dimer]] levels contributing to an increased [[false positive|false positive value]]. Such disease states include [[pneumonia]], [[Congestive heart failure|congestive heart failure (CHF)]], [[Myocardial infarction|myocardial infarction (MI)]] and [[malignancy]]. Additionally, in patients with prolong symptoms of [[venous thromboembolism]] (≥14 days), patients on therapeutic [[heparin|heparin therapy]] and patients with suspected [[deep venous thrombosis]] on oral anticoagulation, the plasma d-dimer levels are considerable lower, resulting in high [[false-negative]] values.<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>
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| ==Sensitivity and 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>==
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| {| border="1"
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| ! Method !! Sensitivity (95% CI) !! Specificity (95% CI) !! Positive Likelihood Ratio (95% CI) !! Negative Likelihood Ratio (95% CI)
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| |-
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| | [[ELISA|Enzyme-linked immunosorbent assay (ELISA)]]
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| | 0.95 (0.85 to 1.00)
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| | NS
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| | NS
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| | 0.13 (0.03 to 0.58)
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| |-
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| | [[ELISA|Quantitative rapid ELISA]]
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| | 0.95 (0.83 to 1.00)
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| | NS
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| | NS
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| | 0.13 (0.02 to 0.84)
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| |-
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| | [[ELISA|Semi-Quantitative rapid ELISA]]
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| | 0.93 (0.79 to 1.00)
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| | NS
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| | NS
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| | 0.20 (0.04 to 0.96)
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| |-
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| | [[ELISA|Qualitative rapid ELISA]]
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| | NS
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| | 0.68 (0.50 to 0.87)
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| | NS
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| | 0.11 (0.01 to 0.93)
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| |-
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| | [[Quantitative Latex]]
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| | NS
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| | NS
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| | NS
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| | NS
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| |-
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| | [[Semi-quantitative Latex]]
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| | NS
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| | NS
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| | NS
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| | 0.17 (0.04 to 0.78)
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| |-
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| | Whole-Blood
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| | NS
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| | 0.74 (0.60 to 0.88)
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| | NS
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| | NS
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| |}
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| ====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>====
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| [[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 whole-blood agglutination.
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| ====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>====
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| [[ELISA|Qualitative rapid ELISA]] has shown to be statistically superior to [[ELISA]] ''(p=0.004)'', [[quatitative rapid ELISA]] ''(p=0.002)'', [[semi-quantitative rapid ELISA]] ''(p=0.001)'', [[latex agglutination|quantitative]] ''(p=0.005)'' and [[latex agglutination|semi-quantitative]] latex agglutination assays ''(p=0.019)''.
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| ==Hemodynamically Stable Patients==
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| ====Incidence of Thromboembolic Events in Hemodynamicaly Stable Patients====
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| {| border="1"
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| ! Condition !! Incidence of thromboembolic event (%)
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| |-
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| | Patients not receiving anticoagulation and with negative CT findings.
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| | 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>
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| |-
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| | Patients with High d-dimer level
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| | 1.5%
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| |-
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| | Patients with Normal d-dimer level
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| | 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>
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| |}
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| *[[Pulmonary embolism CT#Multi-Detector CT|Multidetector CT]] is indicated in hemodynamically stable with high clinical probability and/or patients with elevated plasma d-dimer levels.<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>
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| *In '''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> 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>
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| ==Flowchart summarizing the role of D-dimer in the diagnosis of PE==
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| {{familytree/start |summary=Use of D-Dimer.}}
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| {{familytree | | | | GMa | GMa=Patients with suspection of [[Pulmonary embolism]]}}
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| {{familytree | |,|-|-|^|-|-|-|.| | | }}
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| {{familytree |JOE| | | | |SIS| | | JOE=Clinically Low or Moderate|SIS=Clinically High}}
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| {{familytree |,|^|-|.| | | | |!| }}
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| {{familytree |!| | |!| | | | |!| }}
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| {{familytree |!| | |ME| | |!|ME=D-Dimer Positive}}
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| {{familytree |!| | | |!| | | |!| }}
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| {{familytree |MOM| |!| | | |!| |MOM=D-Dimer Negative|}}
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| {{familytree | |!| | |!| | | |!| }}
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| {{familytree |GPa| |ME| |SIS|GPa=No treatment|ME=Further Tests|SIS=Further Tests}}
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| {{familytree/end}}
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| 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>
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| ==ESC 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>==
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| ===Suspected Non High-risk PE Patients===
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| {{cquote|
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| ====[[European society of cardiology#Classes of Recommendations|Class I]]====
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| '''1.''' Plasma D-dimer measurement is recommended in emergency department patients to reduce the need for unnecessary imaging and irradiation, preferably using a highly sensitive assay. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
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| ====Low clinical probability====
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| ====[[European society of cardiology#Classes of Recommendations|Class I]]====
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| '''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]])''
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| ====Intermediate clinical probability====
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| ====[[European society of cardiology#Classes of Recommendations|Class I]]====
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| '''1.''' Normal D-dimer level using a highly sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])''
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| ====[[European society of cardiology#Classes of Recommendations|Class IIa]]====
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| '''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]])''
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| ====High clinical probability====
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| ====[[European society of cardiology#Classes of Recommendations|Class III]]====
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| '''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]])''}}
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| ==Guideline Resources==
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| [http://eurheartj.oxfordjournals.org/content/29/18/2276.long 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]<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=[[European Heart Journal]] |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=2012-04-26}}</ref>
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| ==References==
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| {{reflist|2}}
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| [[Category:Hematology]]
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| [[Category:Pulmonology]]
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| [[Category:Cardiology]]
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| [[Category:Emergency medicine]]
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| [[Category:Laboratory Tests]]
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| {{WH}}
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| {{WS}}
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