Q&A

Negative ELISA D-dimer assay can miss pulmonary embolism

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  • BACKGROUND: In patients with clinically suspected acute pulmonary embolism, does a negative ELISA D-dimer assay correctly exclude pulmonary embolism? Physicians do not want to miss cases of pulmonary embolism. Because imaging tests to rule out the diagnosis (lung scans, chest computed tomography, or pulmonary angiography) are inexact, expensive, or invasive, physicians seek a sensitive screening assay to reduce the number of patients needing additional testing.
  • POPULATION STUDIED: The authors enrolled all patients presenting to the emergency department of the Brigham and Women’s Hospital during 2000 who were initially evaluated for suspected pulmonary embolism. The authors evaluated 1106 D-dimer levels: 311 from men and 795 from women. They did not define the emergency department physicians’ criteria for suspected pulmonary embolism and did not specify any inclusion or exclusion criteria. The prevalence of pulmonary embolism over the course of the year was 5.0%.
  • STUDY DESIGN AND VALIDITY: This evaluation of the negative predictive value of a normal D-dimer assay mandated that emergency department physicians order the assay for all patients suspected of acute pulmonary embolism. No other procedural change was required in how physicians chose to work up, treat, or follow up suspected pulmonary embolism. Because no imaging test was performed on all subjects as a gold standard for the diagnosis, the authors chose to follow up every subject for 6 months to determine whether pulmonary embolism was subsequently diagnosed.
  • OUTCOMES MEASURED: The primary outcomes were the sensitivity and specificity of the ELISA D-dimer assay (VIDAS assay, bioMerieux) in detecting pulmonary embolism in symptomatic patients presenting to the emergency department.
  • RESULTS: Of 547 patients who screened negative with the D-dimer assay, 2 had acute pulmonary embolism; of 559 positive screens, 53 patients had acute pulmonary embolism. These results translated into a sensitivity of 96.4%, a specificity of 52.0%, a positive predictive value of 9.5%, and a negative predictive value of 99.6%.


 

PRACTICE RECOMMENDATIONS

This evaluation of the use of enzyme-linked immunosorbent assay (ELISA) D-dimer test in routine clinical practice supports other evidence that the assay has a high sensitivity to exclude pulmonary embolism in patient populations in which there is clinical suspicion. Nevertheless, the assay incorrectly excluded the diagnosis of pulmonary embolism in 2 cases.

Other examples of clinical decision-making exist for which the acceptable negative predictive value for screening is set at 100%—eg, the diagnosis of phenylketonuria in newborns.

Physicians who do not want to miss cases of acute pulmonary embolism when they clinically suspect the diagnosis should not rely solely on negative D-dimer assay results when the value to rule out the diagnosis is set at 500 ng/mL. If a lower value is used to define normal—eg, 250 ng/mL, as used in other studies—no cases of acute pulmonary embolism would have been missed in this group of patients. Regardless of the cutoff used, the assay will yield many false-positive results.

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