Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions

Abstract

Patients with inflammatory conditions such as inflammatory bowel disease (IBD), chronic heart failure (CHF), and chronic kidney disease (CKD) have high rates of iron deficiency with adverse clinical consequences. Under normal circumstances, serum ferritin levels are a sensitive marker for iron status but ferritin is an acute-phase reactant that becomes elevated in response to inflammation, complicating the diagnosis. Proinflammatory cytokines also trigger an increase in hepcidin, which restricts uptake of dietary iron and promotes sequestration of iron by ferritin within storage sites. Patients with inflammatory conditions may thus have restricted availability of iron for erythropoiesis and other cell functions due to increased hepcidin expression, despite normal or high levels of serum ferritin. The standard threshold for iron deficiency (<30 μg/L) therefore does not apply and transferrin saturation (TSAT), a marker of iron availability, should also be assessed. A serum ferritin threshold of <100 μg/L or TSAT < 20% can be considered diagnostic for iron deficiency in CHF, CKD, and IBD. If serum ferritin is 100–300 μg/L, TSAT < 20% is required to confirm iron deficiency. Routine surveillance of serum ferritin and TSAT in these at-risk groups is advisable so that iron deficiency can be detected and managed.

Portal hypertensive gastropathy is associated with iron deficiency anemia

“…Anemia was categorized into mild anemia (Hb <13.5 g/dl in men or <12 g/dl in women), moderate anemia (Hb <10 g/dl) and severe anemia (Hb <8 g/dl). As recently proposed for inflammatory conditions [29,30], IDA was defined as anemia (Hb levels beneath gender-adjusted lower limit of normal) together with a ferritin concentration <100 µg/L or transferrin saturation <16%. The PHG was classified by experienced endoscopists according to consensus guidelines [31] in three groups: no PHG, mild PHG, and severe.…”

Comparative accuracy of ferritin, transferrin saturation and soluble transferrin receptor for the diagnosis of iron deficiency in inflammatory bowel disease

“…To date, only four studies have been published examining the clinical value of sTfR or TfR‐F in detecting iron deficiency in IBD 23 . Although these studies 20,23‐25 showed that iron deficiency detection rates with sTfR or TfR‐F are higher than the commonly used markers TfS and ferritin, sTfR is rarely used in routine practice by IBD physicians due to high costs and low availability. The aims of this study were to evaluate the accuracy of currently recommended TfS and/or ferritin cut‐offs for the diagnosis of iron deficiency, using sTfR as the reference due to the inflammation that is present in IBD patients, and to identify the optimal thresholds to predict iron deficiency in a large cohort of patients with IBD.…”

Utility of new red cell parameters for distinguishing functional iron deficiency from absolute iron deficiency in children with familial Mediterranean fever

“…The FMF patients were divided into two subgroups as FMF‐I (+) or FMF‐I (−) according to presence or absence of inflammatory response, as indicated by elevated erythrocyte sedimentation rate and elevated C‐reactive protein (CRP) level. Functional iron deficiency and AID were defined in accordance with the description of iron status, CBC parameters, and CRP level . Absolute iron deficiency was defined as transferrin saturation <20% and ferritin levels <30 ng/mL in association with normal CRP level.…”

“…This form of deficiency occurs when there is insufficient iron transport into erythroid precursors despite sufficient body stores of iron during inflammation. Distinct from FID, absolute iron deficiency (AID) is characterized by low iron stores in patients without inflammation …”

“…Distinct from FID, absolute iron deficiency (AID) is characterized by low iron stores in patients without inflammation. 5,6 Familial Mediterranean fever (FMF) is an autosomal recessive auto-inflammatory disease caused by the Mediterranean fever (MEFV) gene mutation and is characterized by recurrent episodes of fever and serositis. 7 Patients with FMF experience recurrent periods of exacerbation and remission; thus, the clinical course differs from other chronic inflammatory diseases.…”