Utility and limitations of patient‐adjusted D‐dimer cut‐off levels for diagnosis of venous thromboembolism—A systematic review and meta‐analysis

Abstract

AbstractPurposeTo systematically assess test performance of patient‐adapted D‐dimer cut‐offs for the diagnosis of venous thromboembolism (VTE).MethodsSystematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient‐adjusted D‐dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score.ResultsA total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut‐off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98–0.99) and specificity of 0.23 (95% CI 0.16–0.31). Sensitivity was comparable to the standard cut‐off for age‐adjustment (0.97 [95% CI 0.96–0.98]) and YEARS algorithm (0.98 [95% CI 0.91–1.00]) but lower for pretest probability (PTP)‐adjusted (0.95 [95% CI 0.89–0.98) and COVID‐19‐adapted thresholds (0.93 [95% CI 0.82–0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36–0.50]; PTP: 0.63 [95% CI 0.51–0.73]; YEARS algorithm: 0.65 [95% CI 0.39–0.84]; and COVID‐19: 0.51 [95% CI 0.40–0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01–0.15]), followed by age‐adjusted (both 0.07 [95% CI 0.05–0.09]), PTP (0.08 [95% CI 0.04–0.17), and COVID‐19‐adjusted thresholds (0.13 [95% CI 0.05–0.32]).ConclusionsThis study indicates that adjustment of D‐dimer thresholds to patient‐specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.