A negative simpliRED D-Dimer Assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients☆,☆☆
Introduction
Pulmonary embolism (PE) and deep venous thrombosis (DVT) are both clinical presentations of the same disease process, termed venous thromboembolism (VTE). Failure to diagnose and treat VTE places the patient at increased risk of death.1, 2 This prompts physicians to consider the diagnosis even when the likelihood of disease is low. Clinical presentation of VTE is often protean, and confirmatory testing is both difficult to perform and interpret. A rapid, inexpensive, screening test with a high negative predictive value is needed to rule out disease in those patients considered at risk. Assays to measure fibrin degradation products, D -dimers, may provide such a test.
D -dimer levels are elevated in the presence of VTE.3 However, other conditions including sepsis, myocardial infarction, liver disease, and HIV infection can also cause elevations. It follows that D -dimers are sensitive but relatively nonspecific markers for VTE. This has generated considerable interest in development of D -dimer assays with adequate negative predictive value to effectively rule out VTE.
The Food and Drug Administration recently approved the use of the SimpliRED D -dimer assay (American Diagnostica Inc, Greenwich, CT) for the diagnosis of VTE. The SimpliRED assay uses an antibody specific for both D -dimers and RBCs. D -dimer levels in excess of 200 μg/L result in agglutination of whole blood. This assay can be performed at the bedside and provides results within 5 minutes. In previous clinical trials, the SimpliRED assay has demonstrated sensitivity and negative predictive value of 95% to 100% for VTE.4, 5, 6, 7, 8, 9
Our objective was to perform a validation study of the SimpliRED assay in our emergency department population. The study hypothesis was that a negative SimpliRED D -dimer assay result would exclude the diagnosis of VTE in those patients considered at risk for disease.
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Materials and methods
ED patients considered at risk for DVT or PE were consecutively enrolled over a 2-year period (December 1996 through December 1998). The study was conducted at a tertiary care facility with an annual ED census of approximately 62,000 visits. Physicians obtained informed written consent and completed a clinical fact sheet for each patient at the time of enrollment. The fact sheet consisted of patient demographics, risk factors, and pretest probability of disease. The enrolling physician made a
Results
One hundred ninety-eight patients were enrolled during the 2-year study period. Patient ages ranged from 21 to 95 years (mean 55 years). Women comprised 59% of the study population. A total of 25 patients were excluded from data analysis; 16 were lost to follow-up, 8 received alternative diagnoses without any testing for VTE, and 1 with a nondiagnostic V/Q scan and a high pretest probability of PE was given a clinical diagnosis of VTE without any confirmatory testing. A total of 173 patients
Discussion
A screening test is needed for patients considered at risk for VTE. An ideal screening test would require a negative predictive value of at least 95%, provide rapid results (<1 hour), and demonstrate validity at individual institutions. Although a growing body of evidence exists to support the potential role of D -dimers in excluding the diagnosis of VTE, no individual assay has demonstrated the necessary clinical utility to be regarded as an effective screening test.
Current data suggest that
Acknowledgements
We thank Lee Lucas, PhD, statistical consultant, Department of Medical Research, Maine Medical Center, for assistance in statistical analyses.
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Cited by (0)
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Supported by a grant from the Maine Medical Center Research Institute.
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Address for reprints: Scott Farrell, MD, Department of Emergency Medicine, Maine Medical Center, 47 Bramhall Street, Portland, ME 04102;fax 207-772-4036; E-mail [email protected].