Regular ArticleComparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of Pulmonary Embolism
Introduction
D-Dimer assays have an established role in the diagnostic approach of venous thrombo-embolism. D-Dimer test in combination with the determination of clinical pretest probability is increasingly accepted as a first-line test in patients with suspected pulmonary embolism (PE) [1], [2], [3], [4], [5], [6]. Several management studies have shown that PE can be safely ruled out without the need for additional imaging in patients with an unlikely clinical pretest probability according to Wells (Table 1) and a normal D-Dimer test result, occurring in 20% to 40% of patients [6], [7], [8].
When choosing a specific D-Dimer test, it is important to consider both sensitivity and specificity of the assay. Most quantitative D-Dimer tests are very sensitive but specificity is generally relatively poor [9], so that a normal result has high negative predictive value but occurs in a relatively small proportion of patients. Differences between D-Dimer assays are caused by antibody specificity, especially concerning the preference for high- or low-molecular-weight fibrin derivates and for cross-linked and non-cross-linked fibrin derivates [10]. Other causes of discrepancies between D-Dimer assays are thought to be the time-dependency of neo-epitope expression in the course of fibrin formation and dissolution, assay format, purity or heterogeneity of the calibrator, matrix effects of plasma on epitope presentation and interference by irrelevant analysis [11].
Importantly, although there is a wealth of studies evaluating different D-Dimer tests in the setting of venous thrombosis and pulmonary embolism, a comparison between two tests in a clinical outcome study has not been carried out.
We conducted a post-hoc analysis from data that were derived from a prospective cohort study, the Christopher study [6]. Within this study we evaluated the clinical usefulness and test efficiency of the two quantitative D-Dimer tests used in this study, the latex (Tinaquant) D-Dimer test and the quantitative ELISA (VIDAS) plasma D-Dimer test.
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Patients
Consecutive in- and outpatients with clinically suspected pulmonary embolism were eligible for the Christopher study. Patients were excluded if they had received treatment with therapeutic doses of unfractionated or low-molecular-weight-heparin for more than 24 hours, had a life expectancy less than 3 months, were pregnant, had geographic inaccessibility precluding follow-up an age below 18 years, an allergy to intravenous contrast agents, a renal insufficiency (creatinine clearance 30 mL/ min
Results
In the total study population, consisting of 2206 patients, a D-Dimer concentration was measured in 1238 patients using the Tinaquant D-Dimer assay and in 968 patients using the VIDAS D-Dimer assay. The general characteristics of both groups were comparable (Table 2). Of the 1057 patients with a normal D-dimer test result, 29 (11 in the Tinaquant group and 18 in the VIDAS group) were treated with oral anticoagulants during follow-up for other reasons than venous thrombosis. Also, 2 patients
Discussion
This analysis shows that in patients with an unlikely clinical probability of PE according to the Wells Rule, the quantitative Tinaquant and VIDAS D-Dimer tests performed equally well in excluding PE. Both tests had very low VTE failure rates at follow up, 0.62% for the Tinaquant and 0.24% for the VIDAS. Also, in neither group fatal PE occurred during follow-up. Our results are in contrast with earlier studies, in which the VIDAS test was shown to have a better sensitivity and NPV than
Conflict of interest
The authors declare to have no financial disclosure to this manuscript which they should report.
Acknowledgements
The Christopher Study Writing Group consisted of the following investigators in alphabetical order: Arne van Belle, Harry R. Büller, Menno V. Huisman, Peter M. Huisman, Karin Kaasjager, Pieter W. Kamphuisen, Mark H.H. Kramer, Marieke J.H.A. Kruip, Johanna M. Kwakkel-van Erp, Frank W.G. Leebeek, Mathilde Nijkeuter, Martin H. Prins, Maaike Sohne, Lidwine W. Tick.
References (14)
- et al.
A clinical probability assessment and d-dimer measurement should be the initial step in the investigation of suspected venous thromboembolism
Chest
(2003) - et al.
The accuracy of the enzyme-linked immunosorbent assay D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis
Ann Emerg Med
(2002) - et al.
Non-invasive diagnostic work-up of patients with clinically suspected pulmonary embolism: results of a management study
J Thromb Haemost
(2004) - et al.
Sensitivity and Specificity of the Semiquantitative Latex Agglutination D-Dimer Assay for the Diagnosis of Acute Pulmonary Embolism as Defined by Computed Tomographic Angiography
Mayo Clin Proc
(2004) - et al.
Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism: a prospective management study
Arch Intern Med
(2002) - et al.
Clinical practice: the evaluation of suspected pulmonary embolism
N Eng J Med
(2003) British Thoracic Society guidelines for the management of suspected acute pulmonary embolism
Thorax
(2003)