Diagnosing iron deficiency is challenging in the presence of systemic inflammation.

To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome.

Test prospective cohort and validation retrospective cohort.

A prospective cohort of inpatients (n = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n = 795) further assessed the predictive power of this ratio.

In a training cohort (median age 76 years [57–84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57–84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85–0.90], with an odds ratio of 37.9 [95% CI: 20.3–68.9] for the threshold of ≤6.

In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies.