Clinical study
Limitations of D-dimer testing in unselected inpatients with suspected venous thromboembolism

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Abstract

Purpose

To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients.

Methods

We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic evaluation for possible venous thromboembolism. We included patients with a history of malignancy, recent surgery, thrombosis, and anticoagulation treatment. C-reactive protein levels were assayed as a measure of inflammation.

Results

Of 45 patients with radiographically proven proximal deep venous thrombosis or pulmonary embolism, 43 had elevated D-dimer levels by enzyme-linked immunosorbent assay (ELISA) (sensitivity, 96%); the specificity of the test was 23% (36/157). The qualitative non-ELISA tests had higher specificities, but their sensitivities were <70%. Nineteen patients (42%) with thrombosis had false-negative D-dimer tests by at least one assay. The specificity of the tests decreased with increasing duration of hospitalization, increasing age, and increasing C-reactive protein levels. D-dimer testing had little or no utility in distinguishing patients with thrombosis from those without in patients who had been hospitalized for more than 3 days, were older than 60 years, or had C-reactive protein levels in the highest quartile.

Conclusion

In unselected inpatients, D-dimer testing has limited clinical utility because of its poor specificity. This is particularly true for older patients, those who have undergone prolonged hospitalization, and those with markedly elevated C-reactive protein levels. In some patient subsets, a negative non-ELISA D-dimer test cannot discriminate between inpatients with and without thrombosis.

Section snippets

Design and subjects

We conducted a prospective study of patients at Johns Hopkins Hospital who underwent radiologic evaluation for possible venous thromboembolism. The hospital’s institutional review board approved the protocol; informed consent was obtained from all participants. We identified patients by daily review (weekdays only) of radiology scheduling records. Attempts were made to enroll all eligible patients. Any patient who underwent radiologic evaluation for deep vein thrombosis or pulmonary embolism

Results

Subjects were enrolled between November 1999 and December 2000. Of the 250 patients enrolled, laboratory tests and appropriate radiographic studies were completed for 203 patients (81%). Forty-five patients (22%) had thrombosis by radiographic imaging, including pulmonary embolism in 21 patients, deep vein thrombosis alone in 20 patients, and both conditions in 4 patients. Thrombosis was diagnosed by helical CT scan alone in 16 patients, ultrasound examination alone in 18, autopsy in 1,

Discussion

We found that D-dimer testing has limited utility for the exclusion of venous thromboembolism in unselected hospitalized patients, especially in the elderly and in those who have been hospitalized for more than 3 days. The three non-ELISA tests were not useful in distinguishing patients with thrombosis from those without thrombosis among patients 60 years of age or older, or who had been hospitalized for more than 3 days; in other words, a negative D-dimer test did not lower the probability of

Acknowledgements

We thank Rosa Sebree, Jeffrey Mendoza, and Dawn Clark for subject enrollment and chart review; Esther Lipsky for her technical assistance; and Elliot Fishman, Elrike Hamper, Karen Horton, and Richard Rothman for their willingness to facilitate patient enrollment.

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    Dr. Brotman is currently with the Department of General Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.

    This study was supported by funding from the Dade Behring Corporation, Marburg, Germany.

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