A systematic review and meta-analysis of the association between the D-dimer and rheumatic diseases

Introduction

There is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta-analysis of the association between the d-dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association.

Methods

We searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively.

Results

In 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d-dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76−1.10, p < .001; I² = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between-group differences in d-dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C-reactive protein, and erythrocyte sedimentation rate.

Conclusions

Overall, patients with RDs have significantly higher d-dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d-dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d-dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712).