Pulmonary embolism D-dimer: Difference between revisions

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==Overview==
==Overview==
[[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 ''(91-94% when done by ELISA)''. 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]]. The d-dimer levels are considerable lower in patients with symptoms of [[venous thromboembolism]] for over 14 days, patients on therapeutic [[heparin|heparin therapy]] and patients with suspected [[deep venous thrombosis]] on oral anticoagulation giving rise to [[false-negative]] results.<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]] 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]]. The d-dimer levels are considerable lower in patients with symptoms of [[venous thromboembolism]] for over 14 days, patients on therapeutic [[heparin|heparin therapy]] and patients with suspected [[deep venous thrombosis]] on oral anticoagulation giving rise to [[false-negative]] results.<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>


==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>==
==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>==

Revision as of 03:27, 8 May 2012

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

Overview

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 value. Such disease states include pneumonia, congestive heart failure (CHF), myocardial infarction (MI) and malignancy. The d-dimer levels are considerable lower in patients with symptoms of venous thromboembolism for over 14 days, patients on therapeutic heparin therapy and patients with suspected deep venous thrombosis on oral anticoagulation giving rise to false-negative results.[1][2]

Sensitivity and Specificity[3]

Method Sensitivity (95% CI) Specificity (95% CI) Positive Likelihood Ratio (95% CI) Negative Likelihood Ratio (95% CI)
Enzyme-linked immunosorbent assay (ELISA) 0.95 (0.85 to 1.00) NS NS 0.13 (0.03 to 0.58)
Quantitative rapid ELISA 0.95 (0.83 to 1.00) NS NS 0.13 (0.02 to 0.84)
Semi-Quantitative rapid ELISA 0.93 (0.79 to 1.00) NS NS 0.20 (0.04 to 0.96)
Qualitative rapid ELISA NS 0.68 (0.50 to 0.87) NS 0.11 (0.01 to 0.93)
Quantitative Latex NS NS NS NS
Semi-quantitative Latex NS NS NS 0.17 (0.04 to 0.78)
Whole-Blood NS 0.74 (0.60 to 0.88) NS NS

Sensitivity[3]

ELISA (p=0.020), quantitative rapid ELISA (p=0.016) and semi-quantitative ELISA (p=0.047) are shown to be statistically superior to whole-blood agglutination.

Specificity[3]

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), quantitative (p=0.005) and semi-quantitative latex agglutination assays (p=0.019).

Hemodynamically Stable Patients

Incidence of Thromboembolic Events in Hemodynamicaly Stable Patients

Condition Incidence of thromboembolic event (%)
Patients not receiving anticoagulation and with negative CT findings. 1.5%[4][5]
Patients with High d-dimer level 1.5%
Patients with Normal d-dimer level 0.5%[4]
  • Multidetector CT is indicated in hemodynamically stable with high clinical probability and/or patients with elevated plasma d-dimer levels.[5]
  • In low-to-moderate suspicion of PE, a normal D-dimer level is considered sufficient to exclude the possibility of pulmonary embolism.[6] In patients with High clinical probability, the use of the d-dimer assay is of limited value.[7]

Flowchart summarizing the role of D-dimer in the diagnosis of PE

 
 
 
Patients with suspection of Pulmonary embolism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinically Low or Moderate
 
 
 
 
Clinically High
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D-Dimer Positive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D-Dimer Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No treatment
 
Further Tests
 
Further Tests


A new D-Dimer (DDMR) analyzer has shown to have higher accuracy in excluding patients with non-high clinical pre-test probability.[8]

ESC Guideline Recommendations [9]

Suspected Non High-risk PE Patients

Class I

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. (Level of Evidence: A)

Low clinical probability

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

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

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)

Guideline Resources

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[9]

References

  1. Bruinstroop E, van de Ree MA, Huisman MV (2009). "The use of D-dimer in specific clinical conditions: a narrative review". Eur J Intern Med. 20 (5): 441–6. doi:10.1016/j.ejim.2008.12.004. PMID 19712840.
  2. Agnelli G, Becattini C (2010). "Acute pulmonary embolism". N Engl J Med. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294.
  3. 3.0 3.1 3.2 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. 4.0 4.1 Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL; et al. (2005). "Multidetector-row computed tomography in suspected pulmonary embolism". N Engl J Med. 352 (17): 1760–8. doi:10.1056/NEJMoa042905. PMID 15858185. in: J Fam Pract. 2005 Aug;54(8):653, 657
  5. 5.0 5.1 van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW; et al. (2006). "Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography". JAMA. 295 (2): 172–9. doi:10.1001/jama.295.2.172. PMID 16403929.
  6. Bounameaux H, de Moerloose P, Perrier A, Reber G (1994). "Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview". Thromb. Haemost. 71 (1): 1–6. PMID 8165626.
  7. Gupta RT, Kakarla RK, Kirshenbaum KJ, Tapson VF (2009). "D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism". AJR Am J Roentgenol. 193 (2): 425–30. doi:10.2214/AJR.08.2186. PMID 19620439.
  8. Gosselin RC, Wu JR, Kottke-Marchant K, Peetz D, Christie DJ, Muth H; et al. (2012). "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". Thromb Res. doi:10.1016/j.thromres.2011.12.015. PMID 22245223.
  9. 9.0 9.1 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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