title: Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.
abstract: Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD.
authors.affiliation: Division of Hematology, University of Kansas Medical Center, Kansas City, USA. bskikne@celgene.com
authors.forename: Barry S
authors.initials: BS
authors.lastname: Skikne
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Paul H
authors.initials: PH
authors.lastname: Caldron
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bennett
authors.forename: Mari
authors.initials: M
authors.lastname: Rehu
authors.forename: Gail H
authors.initials: GH
authors.lastname: Gasior
authors.forename: Janna S
authors.initials: JS
authors.lastname: Chamberlin
authors.forename: Linda A
authors.initials: LA
authors.lastname: Sullivan
authors.forename: Kurtis R
authors.initials: KR
authors.lastname: Bray
authors.forename: Paula C
authors.initials: PC
authors.lastname: Southwick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D002908:Chronic Disease; D003937:Diagnosis, Differential; D005260:Female; D005293:Ferritins / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D011990:Receptors, Transferrin / Q000032:analysis*; D012995:Solubility; D014168:Transferrin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins