Pulmonary embolism D-dimer
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Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]
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 (CHF), myocardial infarction (MI) and malignancy. False-negative values may occur in patients with prolonged symptoms of venous thromboembolism (≥14 days), patients on therapeutic 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.[1][2]
D-dimer
Abnormal Levels
Plasma D-dimer levels > 500 ng/mL are abnormal.[3]
Sensitivity and Specificity
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), quantitative 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).
| Method | Sensitivity (95% CI) | Specificity (95% CI) | Positive Likelihood Ratio (95% CI) | Negative Likelihood Ratio (95% CI) | Time to obtain Results |
|---|---|---|---|---|---|
| Enzyme-linked immunosorbent assay (ELISA) | 0.95 (0.85 to 1.00) | NS | NS | 0.13 (0.03 to 0.58) | ≥ 8 hours |
| Quantitative rapid ELISA | 0.95 (0.83 to 1.00) | NS | NS | 0.13 (0.02 to 0.84) | 30 mins |
| Semi-Quantitative rapid ELISA | 0.93 (0.79 to 1.00) | NS | NS | 0.20 (0.04 to 0.96) | 10 mins |
| Qualitative rapid ELISA | NS | 0.68 (0.50 to 0.87) | NS | 0.11 (0.01 to 0.93) | 10 mins |
| Quantitative Latex Agglutination | NS | NS | NS | NS | 10-15 mins |
| Semi-quantitative Latex Agglutination | NS | NS | NS | 0.17 (0.04 to 0.78) | 5 mins |
| Whole-Blood Agglutination | NS | 0.74 (0.60 to 0.88) | NS | NS | 2 mins |
Hemodynamically Stable Patients
Incidence of Thromboembolic Events in Hemodynamically Stable Patients
| Condition | Incidence of thromboembolic event (%) |
|---|---|
| Patients not receiving anticoagulation with negative CT findings. | 1.5%[4][5] |
| Patients with a high d-dimer level | 1.5% |
| Patients with a normal d-dimer level | 0.5%[4] |
- 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.[5][6]
- In patients with low-to-moderate suspicion of PE, a normal D-dimer level is considered sufficient to exclude the possibility of pulmonary embolism.[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 be more accurate in excluding patients with a low clinical pre-test probability.[8]
ESC 2008 Guideline Recommendations [9]
Suspected Non High-risk PE Patients (DO NOT EDIT)[9]
| 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)[9]
| 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)[9]
| 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)[9]
| 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
- ↑ 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.
- ↑ Agnelli G, Becattini C (2010). "Acute pulmonary embolism". N Engl J Med. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294.
- ↑ 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) - ↑ 4.0 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
- ↑ 5.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 9.0 9.1 9.2 9.3 9.4 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)