Towards a Common Definition for the Diagnosis of Iron Deficiency in Chronic Inflammatory Diseases

Abstract

Iron deficiency (ID) in patients with chronic inflammatory diseases is frequent. However, under-diagnosis is also frequent due to the heterogeneity between guidelines from different medical societies. We applied a common definition for the diagnosis of ID to a large panel of patients with cancer, heart failure (HF), inflammatory bowel disease (IBD), and chronic kidney disease (CKD), where ID was defined as serum ferritin concentration <100 μg/L and/or a transferrin saturation (TSAT) index <20%. Prevalence estimates using this common definition were compared with that obtained with officially accepted definitions (ESMO 2018, ESC 2016, ECCO 2015, and ERBP 2013). For that purpose, we used data collected during the French CARENFER studies, which included 1232, 1733, 1090, and 1245 patients with cancer, HF, IBD, and CKD, respectively. When applying the common definition, ID prevalence increased to 58.1% (vs. 57.9%), 62.8% (49.6%), and 61.2% (23.7%) in cancer, HF, and IBD patients, respectively. Both prevalence estimates were similar (47.1%) in CKD patients. Based on our results, we recommend combining both ferritin concentration and TSAT index to define ID in patients with chronic inflammatory diseases. In those patients, adopting this common definition of ID should contribute to a better screening for ID, whatever the condition.

Prognostic Value of Serum Transferrin Analysis in Patients with Ovarian Cancer and Cancer-Related Functional Iron Deficiency: A Retrospective Case–Control Study

“…The results obtained in the present study are in accordance with the data described in the literature on transferrin and ferritin as negative and positive reactants of the acute phase of inflammation, respectively [12,31,49]. During the development of cancer, the ferritin concentration increases, and the transferrin concentration decreases, often regardless of iron status, and iron deficiency can be diagnosed with ferritin values exceeding 50 µg/L [50,51]. In our study, the reference interval of Tf values (2-3.6 g/L) was established in 73 CrO patients, 2 patients were found to have elevated transferrin levels, and 43 (36%) individuals were determined to have reduced transferrin values.…”

“…In a malignant disease, interpreting the type of iron deficiency on the basis of ferritin concentrations and TSAT is not an easy task. International guidelines for the diagnosis of iron deficiency in chronic inflammation are heterogeneous, and, depending on the disease, the threshold values of ferritin and TSAT differ [50]. In the absence of inflammation and cancer, ferritin levels less than 30 µg/L are the most specific test for detecting iron deficiency in the body [25].…”

The association between iron deficiency and outcomes: a secondary analysis of the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial

“…or patient comorbidities such as diabetes, renal or cardiac disease [12]. Similar diagnostic limitations are also seen with the use of transferrin saturations and there is no consensus on the definitions of absolute/functional/ inflammatory iron deficiency or anaemia of chronic disease [8].…”

“…Serum ferritin is critical in defining absolute iron deficiency. However, ferritin can be elevated due to its role as an acute phase protein during inflammation, due to the illness for which the patient is undergoing surgery (often malignancy) or patient comorbidities such as diabetes, renal or cardiac disease [ 12 ]. Similar diagnostic limitations are also seen with the use of transferrin saturations and there is no consensus on the definitions of absolute/functional/inflammatory iron deficiency or anaemia of chronic disease [ 8 ].…”

Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action

“…Since the reliability of serum ferritin measurement may be compromised in patients with chronic diseases or any inflammatory condition, there is a large consensus in guidelines to determine both serum ferritin and TSAT in the first line. There is still no consensus on the thresholds, but recent recommendations of international guidelines have shown agreement for defining ID by serum ferritin <100 µg/L and/or TSAT <20% [5][6][7][8].…”