Ferritin/TfR ratio in anaemia discrimination: Review Article

Background: Differentiating iron deficiency anaemia (IDA) from anaemia of chronic disease (ACD) in hospitalised adults is a clinically critical yet diagnostically challenging task. Conventional iron indices, especially serum ferritin, are confounded by inflammatory acute-phase responses, reducing their reliability in patients with co-existing inflammatory or malignant conditions. The serum ferritin-to-transferrin receptor ratio (Ferritin/TfR ratio) operationalised as the soluble transferrin receptor to log-ferritin index (TfR-F index) has emerged as a composite biomarker that integrates iron store assessment with cellular iron demand, offering superior discrimination in inflammatory clinical contexts.

Objectives: This review critically evaluates the biochemical basis, diagnostic performance, comparative utility, and clinical integration of the Ferritin/TfR ratio in distinguishing IDA from ACD in hospitalised adult patients and identifies key gaps and future research priorities.

Methods: A structured narrative review of peer-reviewed literature was conducted across PubMed/MEDLINE, EMBASE, Scopus, and Web of Science (1990–2024). Studies reporting diagnostic accuracy metrics (AUC, sensitivity, specificity, positive and negative predictive values) for sTfR, ferritin, and composite indices in IDA/ACD differentiation were identified, critically appraised, and synthesised.

Results: Soluble transferrin receptor (sTfR) concentrations are unaffected by the acute-phase inflammatory response and are significantly elevated in IDA and ACD/IDA but normal or minimally elevated in pure ACD. The TfR-F index (sTfR/log ferritin) consistently outperforms individual markers, achieving AUC values of 0.87–1.00 across diverse patient populations and study designs. In the diagnostically challenging ferritin grey zone (10–100 ng/mL), where conventional ferritin loses discriminative utility, the TfR-F index achieves AUC values of 0.962–0.994. Validated performance is demonstrated in rheumatoid arthritis, inflammatory bowel disease, chronic kidney disease, and other inflammatory conditions prevalent among hospitalised adults.

Conclusion: The Ferritin/TfR ratio represents a robust, inflammation-independent composite biomarker for discriminating IDA from ACD in hospitalised adults. Integration of the TfR-F index into clinical diagnostic algorithms, particularly for patients with ambiguous ferritin values in inflammatory contexts, is strongly warranted. Assay standardisation, population-specific cut-off derivation, and prospective longitudinal studies constitute the most pressing research priorities.