D-dimer and DVT

abstract & commentary

Source: Lee AYY, et al. Clinical utility of a rapid whole-blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis. Ann Intern Med 1999; 131:417-423.

There have been several studies suggesting that certain D-dimer assays have high negative predictive values (NPV) for the diagnosis of deep venous thrombosis (DVT) in a general population of outpatients with suspected DVT.1,2 However, there are also data to suggest that the accuracy of this test in patients with illnesses such as infection, liver disease, and cancer is reduced. This study by the McMaster group compares the clinical utility of a whole blood D-dimer assay (SimpliRed assay) for the diagnosis of DVT in patients with and without cancer.

This was a retrospective analysis of data collected in three prospective studies between 1992 and 1997. In all three studies, D-dimer testing was performed at presentation as part of a diagnostic algorithm that included other tests such as impedance plethysmography, compression ultrasonography, venography, and the assessment of pretest probability. In all three studies, cancer status was recorded at enrollment and before diagnostic testing. To obtain more information on cancer history, charts were reviewed independently by two reviewers who were blinded to D-dimer test results and final DVT status. The sensitivity, specificity, positive and negative predictive values, and likelihood ratios were calculated for the D-dimer assay in patients with and without cancer.

A total of 1068 patients were included in the analysis. The prevalence of DVT was 49% in 121 patients with cancer and 15% in 947 patients without cancer (P < 0.001). The NPV was significantly lower in patients with cancer (79% [CI 62.7-90.4]) than in patients without cancer (97% [CI 94.9-97.8]). This significant difference in NPV occurred despite similar sensitivities in the two patient groups (86% [CI 75.0-94.0] in patients with cancer and 83% [CI 75.2-88.5] in patients without cancer). Of the patients with cancer and a negative D-dimer result, 21% had DVT.

Comment by Stephanie B. Abbuhl, MD, facep

This study clearly shows how the prevalence of a disease can impact the clinical utility of a test by influencing the positive and negative predictive values. Despite its high NPV in patients without cancer, the SimpliRed D-dimer test does not have the same high NPV in patients with cancer, and a negative test cannot be used to reliably exclude DVT in these patients. There may still be a role for D-dimer testing in certain patient groups or in combination with other tests, but additional prospective studies are needed to clarify who, how, and when to use this test in a DVT or pulmonary embolism work-up. This study illustrates the importance of evaluating the performance of a diagnostic test in different patient populations before it is adopted for widespread use.

References

1. Ginsberg JS, et al. Sensitivity and specificity of a rapid whole blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Intern Med 1998;129:1006-1011.

2. Perrier A, et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353:190-195.

In the recent study by Lee et al comparing the clinical utility of a whole blood D-dimer assay (SimpliRed assay) in patients with and without cancer, the authors found:

a. the prevalence of DVT to be almost 50% in patients with cancer undergoing a DVT evaluation compared to 15% in patients without cancer.

b. the negative predictive value of the SimpliRed D-dimer assay in patients with and without cancer was about the same.

c. the SimpliRed D-dimer assay can be used to exclude DVT in patients with cancer.

d. that of the patients with cancer and a negative D-dimer test, only 2% had DVT.