Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis

Abstract

Objective: To review the evidence on the diagnostic accuracy of the currently available point of care D-dimer tests for excluding venous thromboembolism.

Design: Systematic review of research on the accuracy of point of care D-dimer tests, using bivariate regression to examine sources of variation and to estimate sensitivity and specificity.

Data sources: Studies on the diagnostic accuracy of point of care D-dimer tests published between January 1995 and September 2008 and available in either Medline or Embase. Review methods The analysis included studies that compared point of care D-dimer tests with predefined reference criteria for venous thromboembolism, enrolled consecutive outpatients, and allowed for construction of a 2x2 table.

Results: 23 studies (total number of patients 13 959, range in mean age 38-65 years, range of venous thromboembolism prevalence 4-51%) were included in the meta-analysis. The studies reported two qualitative point of care D-dimer tests (SimpliRED D-dimer (n=12) and Clearview Simplify D-dimer (n=7)) and two quantitative point of care D-dimer tests (Cardiac D-dimer (n=4) and Triage D-dimer (n=2)). Overall sensitivity ranged from 0.85 (95% confidence interval 0.78 to 0.90) to 0.96 (0.91 to 0.98) and overall specificity from 0.48 (0.33 to 0.62) to 0.74 (0.69 to 0.78). The two quantitative tests Cardiac D-dimer and Triage D-dimer scored most favourably.

Conclusions: In outpatients suspected of venous thromboembolism, point of care D-dimer tests can contribute important information and guide patient management, notably in low risk patients (that is, those patients with a low score on a clinical decision rule).

Fig 1 Flowchart of included studies. *Instead an aetiological study; for example, a study on risk factors for venous thromboembolism or number of ventilation-perfusion lung scans ordered as a function of D-dimer testing. †Studies investigating other biomarkers, such as P-selectin, or other tests, such as electrocardiography. ‡Studies that did not use venous thromboembolism as the outcome, but aortic dissection or mesenterial thrombosis, for example. §156 of 203 studies were found in both Embase and Medline. ¶For example, because D-dimer testing was only performed in patients with a positive ultrasonogram. **One study compared three different point of care D-dimer tests. Abbreviations: POC, point of care; VTE, venous thromboembolism

Fig 2 Proportion of all 14 Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool criteria that were fulfilled

Fig 3 Receiver operating characteristic graphs with 95% confidence region and 95% prediction region for SimpliRED, Clearview Simplify, and Cardiac D-dimer. The pooled sensitivity of SimpliRED, Clearview Simplify, and Cardiac D-dimer was 0.85, 0.87, and 0.96, respectively; pooled specificity was 0.74, 0.62, and 0.57, respectively. Pooled sensitivity and specificity could not be calculated using the bivariate model for Triage D-dimer owing to the small number of studies assessing this test; the traditional sample size weighted approach yielded an average sensitivity of 0.93 and specificity of 0.48. Abbreviation: HSROC, hierarchical summary receiver operating characteristic

Fig 4 Fagan’s nomogram for Cardiac D-dimer (dashed red line) and Clearview Simplify D-dimer (solid blue line), with a fixed post-test probability of 2%. If post-test probability is fixed at the accepted safety standard of 2%, Cardiac D-dimer can exclude venous thromboembolism in patients with a pre-test probability of up to 27%, compared with 9% with Clearview Simplify D-dimer. For other pre-test probabilities, the post-test probability can be calculated by simply drawing a line through the negative likelihood ratio of the respective point of care D-dimer test (see table 3) and the chosen pre-test probability