From misinterpretation to evidence-informed clinical assessment: optimizing the use of D-dimer in childhood immunoglobulin A vasculitis

Abstract Background A D-dimer is frequently elevated during acute childhood immunoglobulin A vasculitis (IgAV), but this finding is often misinterpreted as direct evidence of thrombosis. This review examines its mechanistic basis, clinical associations, limitations, and appropriate role in risk assessment. Methods This narrative review used a systematic search of PubMed, Web of Science Core Collection, Scopus, and the Cochrane Library from inception to August 26, 2026. Of 262 records identified, 156 remained after deduplication; the evidence map comprised 33 core childhood records and 28 supportive records. Findings were synthesized narratively because clinical outcomes, sampling, assays, reporting units, and statistical methods were heterogeneous. Results Immune-complex- and complement-mediated endothelial injury may activate coagulation and compensatory fibrinolysis; accordingly, D-dimer elevation is generally more consistent with inflammation-associated coagulation activation and secondary fibrin turnover. Its most consistent clinical association was with acute systemic and gastrointestinal activity, including gastrointestinal bleeding and intussusception. Associations with renal involvement were inconsistent and sensitive to sampling time, phenotype definition, biopsy selection, treatment, and assay heterogeneity. Published cutoffs were not interchangeable across analytical platforms, units, FEU/DDU calibrations, or sampling windows. No prospective evidence showed that D-dimer-guided treatment improves outcomes. Isolated elevation confirms neither venous thromboembolism nor disseminated intravascular coagulation and does not justify routine imaging or anticoagulation. Conclusions D-dimer should be interpreted only as an adjunct to clinical and organ-specific assessment. We propose a clinical-first conceptual framework in which symptoms, hemodynamic status, urinalysis, organ function, and targeted imaging guide management, while the D-dimer is interpreted relative to the local assay-specific upper limit of normal and its temporal trend. This framework is not a validated prediction rule or practice guideline.