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Discriminating Between Iron Deficiency Anemia and Anemia of Chronic Disease Using Traditional Indices of Iron Status vs Transferrin Receptor Concentration

[Am J Clin Pathol 115(1):112-118, 2001. © 2001 American Society of Clinical Pathologists, Inc]


Table 1. Classic Distinguishing Features of IDA and ACD*


VariableIron Deficiency AnemiaAnemia of Chronic Disease
EpidemiologyMost common overallMost common in hospitalized patients
Type of anemiaNormocytic-normochromic (early stage);
microcytic-hypochromic (later stage)
Normocytic-normochromic (60%-70% of cases);
microcytic-hypochromic (30%-40% of cases)
Principal lesionAnemia secondary to a lack of adequate
iron
Suppression of erythropoiesis by mediators
of an inflammatory response
Erythrocyte sedimentation rate<-->
Hematocrit, %<31-32 (<0.31-0.32)28-32 (0.28-0.32)
Mean corpuscular volume<-->
Mean corpuscular hemoglobin<-->
Mean corpuscular hemoglobin concentration<-->
RBC distribution width (>14%)<--> to
Serum iron concentration
Total iron binding capacity
Transferrin saturation (%) (<10-15) to <-->
Ferritin concentration, ng/mL (µg/L) (<10 [<10])
Free erythrocyte protoporphyrin concentration<--> to
Stainable marrow ironAbsentPlentiful

, decreased; , increased; <-->, within normal limits.
* Adapted from Cook and Skikne,[23] Worwood,[24] Duffy,[28] and Allen et al.[29]
Value(s) in parentheses are typical for this variable.


Table 2. Summary of Iron and Hematology Indices in Study Subjects With IDA or ACD *


 Group  
VariableIDAACDReference IntervalP
Serum iron concentration, µg/L153 ± 79167 ± 93F, 260-1,700; M, 760-1,980.4885
TIBC, mg/L4.32 ± 0.841.98 ± 0.552.62-4.74<.0001
Transferrin saturation, %3.7 ± 2.29.0 ± 4.520-50<.0001
Ferritin concentration, ng/mL (µg/L)6.7 ± 4.4 (6.7 ± 4.4)1,052.0 ± 970.6
(1,052.0 ± 970.6)
F, 12-160 (12-160);
M, 18-250 (18-250)
<.0001
RBC count, ´ 10[6] /µL (´ 10[12] /L)3.8 ± 0.7 (3.8 ± 0.7)3.2 ± 0.6 (3.2 ± 0.6)F, 3.8-5.5 (3.8-5.5);
M, 4.3-6.2 (4.3-6.2)
.0011
Hemoglobin concentration, g/dL (g/L)8.8 ± 2.0 (88 ± 20)9.5 ± 1.7 (95 ± 17)F, 12.0-15.2 (120-152);
M, 13.2-15.2 (132-152)
.0936
Hematocrit, %27.4 ± 5.8 (0.27 + 0.6)28.3 ± 5.0 (0.28 ± 0.05)F, 37-46 (0.37-0.46);
M, 40-52 (0.40-0.52)
.4761
Mean corpuscular volume, µm[3] (fL)72.6 ± 9.8 (72.6 ± 9.8)87.5 ± 7.8 (87.5 ± 7.8)F, 79-101 (79-101);
M, 82-105 (82-105)
<.0001
Mean corpuscular hemoglobin, pg23.3 ± 3.929.5 ± 2.9F, 27-33; M, 28-34<.0001
Mean corpuscular hemoglobin concentration,
g/dL (g/L)
32.0 ± 1.3 (320 ± 13)33.7 ± 0.7 (337 ± 7)31-35 (310-350)<.0001
RBC distribution width, %18.4 ± 5.114.0 ± 1.811.5-13.5<.0001

ACD, anemia of chronic disease; IDA, iron deficiency anemia.
* Data are given as mean ± SD unless otherwise indicated.
IDA vs ACD group by unpaired Student t-test analysis.


Table 3. Cutoff Values That Optimize the Diagnostic Accuracy of Selected Variables for Discriminating Between Patients With IDA (n = 41) and ACD (n = 31)*


VariableAUCPCutoffSensitivity (%)Specificity (%)PPV (%)NPV (%)
TIBC0.993.164*3.15 mg/L92.7100.0100.091.2
TfR0.958.04529.5 nmol/L92.783.988.489.7
MCV0.873.50179.8 µm[3] (79.8 fL)80.583.986.876.5
%TS0.834.996§6%92.761.376.086.4
RDW0.834<.001||14.8%75.677.481.670.6
SIC0.535 -- 140 µg/L51.264.565.650.0

ACD, anemia of chronic disease; AUC, area under the curve; IDA, iron deficiency anemia; MCV, mean corpuscular volume; NPV, negative predictive value; PPV, positive predictive value; RDW, RBC distribution width; SIC, serum iron concentration; TfR, transferrin receptor; TIBC, total iron binding capacity; %TS, percent transferrin saturation.
* AUC for TIBC vs TfR.
AUC for TfR vs MCV.
AUC for MCV vs %TS.
§ AUC for %TS vs RDW.
|| AUC for RDW vs SIC.