Revisiting D-dimer in periprosthetic joint infection: a comprehensive systematic review and meta-analysis with...

D-dimer has gained considerable attention since its inclusion as a minor criterion in the 2018 International Consensus Meeting. However, evidence regarding its diagnostic accuracy for periprosthetic joint infection (PJI) remains inconclusive. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of D-dimer in diagnosing PJI and comprehensively explore the sources of heterogeneity.

The PubMed, Scopus, Web of Science, Embase, and Cochrane library were systematically searched from their inception to 10 May 2025. Studies that evaluated D-dimer in serum or plasma for the diagnosis of PJI were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup analyses and meta-regression were performed to investigate sources of heterogeneity. Sensitivity analysis evaluated the robustness of the results, and publication bias was examined using Deeks' funnel plot. We assessed the certainty of the evidence for the pooled diagnostic accuracy estimates using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

This study encompassed 30 studies involving 6444 patients. The results of the quality assessment indicate that the majority of the literature was deemed acceptable. The aggregated sensitivity and specificity of D-dimer in diagnosing PJI were 0.74 [95% confidence interval [CI] 0.69-0.79] and 0.72 (95% CI 0.66-0.77), respectively. The summary receiver operating characteristic curve analysis yielded an area under the curve of 0.79 (95% CI 0.76-0.83). Meta-regression identified specimen type, infection type, surgical site, study design, sample size, and gold standard as major sources of heterogeneity; however, substantial residual heterogeneity persisted after multivariable analysis.

This systematic review and meta-analysis demonstrate that, based on low-to-moderate certainty evidence, D-dimer is best used as an initial triage tool or adjunctive rule-out test for PJI, particularly in lower-prevalence settings. Subgroup analyses and meta-regression suggest better diagnostic performance in serum assays, chronic infections, and knee PJI. High-certainty evidence supports the use of D-dimer in combination with C-reactive protein in a serial testing strategy to confirm PJI. Future studies should include large, prospective, multicenter diagnostic cohorts with rigorous methods, minimal missing data, and standardized laboratory reporting to strengthen the evidence base for D-dimer as a diagnostic criterion.