Iron Status Assessment in Geriatric Elderly

In elderly adults, anemia is common and multifactorial. Inflammation, which is frequently observed in hospitalized elderly patients, profoundly alters iron metabolism, making it difficult to accurately assess true iron status.

The objective of this study is to identify a predictive model that can estimate iron deficiency status in the absence of inflammation using transferrin saturation (TSAT) measured during an inflammatory phase. This model could help distinguish true iron deficiency from anemia of inflammation, improve patient management, and reduce decision-making delays.

The study will be conducted in two distinct phases:

• Pilot phase: A prospective, observational, single-center study enrolling up to 200 patients or conducted over a maximum recruitment period of one year, whichever occurs first.
• Main phase: A prospective, observational, multicenter study with the consecutive enrollment of 1,523 patients, including patients enrolled during the pilot phase.

The primary objective of the pilot phase is to estimate the proportion of patients with iron deficiency, defined as a transferrin saturation (TSAT) < 20%, in order to confirm the prevalence assumption that will be used in the sample size calculation for the development of a predictive model of iron deficiency in the absence of inflammation.

The primary objective of the main phase is to develop and validate a predictive model for iron deficiency, defined according to the TSAT threshold in a non-inflammatory setting, with non-inflammation defined as a C-reactive protein (CRP) level < 10 mg/L (or < 20 mg/L depending on results of the pilot phase). The model will be based on measurements obtained during an acute inflammatory state in order to predict iron deficiency.

Eligible participants will be patients aged over 75 years who are hospitalized and present an acute inflammatory episode (CRP > 50 mg/L).

In addition to the routine examinations performed during hospitalization, supplementary analyses will be conducted. After admission (Day -1), patients will receive standard care from the medical team. On the day of admission (Day -1) or the following day (Day 0), patients, their trusted representatives, or relatives will be informed about the study. If the patient fulfils the eligibility criteria, he will be enrolled in the study.

Research-specific analyses will be performed on the following blood samples:

• Day 0 : blood tests (pilot phase and main study): reticulocyte count, reticulocyte hemoglobin content (Ret-He), percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (TSAT, %), ferritin, soluble transferrin receptor, and hepcidin.
• When C-reactive protein (CRP) is < 20 mg/L (pilot phase only): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase.
• When CRP is < 10 mg/L (pilot phase and main study): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase.
• Five days after a CRP value < 10 mg/L (pilot phase and main study, optional): reticulocyte count, reticulocyte hemoglobin content, percentage of hypochromic red blood cells, Delta-He, serum iron, transferrin, transferrin saturation (%), ferritin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, albumin, and creatine phosphokinase.

These additional analyses will be performed using routine blood samples collected during standard clinical monitoring and will not require any additional blood samples. They constitute the main research-specific intervention beyond standard clinical practice.

The objective is to develop a simple and validated tool to estimate transferrin saturation (TSAT), and potentially ferritin levels, in the absence of inflammation using data obtained during the acute inflammatory phase. This tool could help shorten hospital stays, optimize iron therapy prescribing, and improve the management of hospitalized elderly patients.

Inclusion criteria

• Age ≥ 75 years.
• Hospitalization with CRP > 50 mg/L at admission.
• Non-opposition expressed by patient or legally authorized representative

Exclusion criteria

• Advanced chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m²) or chronic dialysis.
• Severe hepatic impairment (Child-Pugh score B or C).
• Severe hematological disorders (active hematologic malignancy or known myelodysplastic syndrome) or known iron metabolism disorders that may bias the study results (e.g., thalassemia, advanced hemochromatosis).
• Hemoglobin < 9g/L
• Treatment with intravenous iron within 12 weeks or oral iron within 4 weeks prior to enrollment.
• Blood transfusion within 3 months prior to enrollment
• Ongoing treatment with erythropoiesis-stimulating agents.
• Ongoing cytotoxic chemotherapy.
• Active bleeding at the time of enrollment.
• Very limited life expectancy or inability to ensure follow-up (end-of-life care).
• Participation in another investigational medicinal product study