Assessment of iron status is a good illustration of using tighter ranges to identify early subclinical deficiencies that are likely to progress to disease.[i]
Biomarker values decrease in iron deficiency much earlier than clinical symptoms appear. Early biochemical changes are reflected in the defined stages of iron deficiency anemia. Noticeable physical symptoms may not appear until stage 5 (Merck Manual).
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Stage 1
|
Decreased stores of bone marrow iron Ferritin drops below 20 ng/mL (45 pmol/L)
Serum iron and hemoglobin within normal limits
|
|
Stage 2
|
Impaired erythropoiesis
Serum iron falls below 50 ug/dL (9 umol/L)
Transferrin saturation drops below 16%
Serum transferrin receptor level rises above 8.5 mg/L
Transferrin increases
|
|
Stage 3
|
Anemia with normal-appearing red blood cells
|
|
Stage 4
|
Microcytosis and hypochromia develop
|
|
Stage 5
|
Deficiency of iron affects tissue, manifests in physical signs and symptoms, including dizziness, fatigue, weakness, loss of stamina, pallor, and restless leg syndrome.
|
A review of the research indicates that healthy individuals with replete bone marrow stores of iron maintained a serum ferritin level of 70 ng/mL.[ii] However, ferritin levels can vary significantly with pathologies such as rheumatoid arthritis, alcoholism, and blood disorders so a comprehensive history and clinical assessment must accompany an evaluation of iron status.
Since low ferritin may be the earliest sign of iron insufficiency, research suggests a low-end cut-off of 30 ng/mL.[iii] However, researchers suggest that ferritin below 100 ng/mL may warrant further evaluation of iron insufficiency. Other biomarkers should be evaluated as well, including mean corpuscular volume, hemoglobin, hematocrit, TIBC, and transferrin saturation as serum iron alone is insufficient for assessing status. At present, serum erythropoietin and hepcidin are being evaluated as pertinent biomarkers.[iv]
Serum ferritin can also be used to assess iron overload as ferritin reflects liver stores which can be damaging at high levels. Ferritin above 160 ng/mL may be indicative of mild iron overload, and 290 ng/mL may indicate severe iron overload.[v] Ferritin levels can increase temporarily during inflammation and infection. Therefore, further assessment of elevated ferritin is warranted.
Reference Intervals and Optimal Ranges
| |
Mosby’s[vi]
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Merck Manual[vii]
|
Quest standard ranges[viii]
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Optimal Ranges
|
|
Serum
Iron
|
Men
80-180 ug/dL
14-32 umol/L
Women
60-160 ug/dL
11-29
umol/L
|
Men
75-150 ug/dL
13–27 umol/L
Women
60–140 ug/dL
11–25 umol/L
|
Men
50-195 ug/dL
9-35
umol/L
Women
40-190 ug/dL
7-34 umol/L
|
85-130 ug/dL
15-23 umol/L
|
|
Total iron-binding capacity (TIBC)
|
250-460 ug/dL
45-82 umol/L
|
250–450 μg/dL
45–81 umol/L
|
250–425 ug/dL
45–76 umol/L
|
250–350 ug/dL
45-76 umol/L
|
|
Ferritin
|
Men
12-300 ng/mL
27-674 pmol/L
Women
10-150 ng/mL
22-337 pmol/L
|
30–300 ng/mL
67-674 pmol//L
|
Men
24-380 ng/mL
54-854 pmol/L
Women
16-288 ng/mL
36-647 pmol/L
|
30–70 ng/mL
67-157 pmol/L
|
|
Transferrin saturation
|
Men
20-50%
Women
15-50%
|
20–50%
|
Men
20–48%
Women
16-45%
|
24–35%
|
References
[i] Camaschella, Clara. “Iron-deficiency anemia.” The New England journal of medicine vol. 372,19 (2015): 1832-43. doi:10.1056/NEJMra1401038
[ii] Garcia-Casal, Maria Nieves et al. “Are Current Serum and Plasma Ferritin Cut-offs for Iron Deficiency and Overload Accurate and Reflecting Iron Status? A Systematic Review.” Archives of medical research vol. 49,6 (2018): 405-417. doi:10.1016/j.arcmed.2018.12.005
[iii] Daru, Jahnavi et al. “Serum ferritin as an indicator of iron status: what do we need to know?.” The American journal of clinical nutrition vol. 106,Suppl 6 (2017): 1634S-1639S. doi:10.3945/ajcn.117.155960
[iv] Peyrin-Biroulet, Laurent et al. “Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review.” The American journal of clinical nutrition vol. 102,6 (2015): 1585-94. doi:10.3945/ajcn.114.103366
[v] Rostoker, Guy et al. “Reassessment of Iron Biomarkers for Prediction of Dialysis Iron Overload: An MRI Study.” PloS one vol. 10,7 e0132006. 16 Jul. 2015, doi:10.1371/journal.pone.0132006
[vi] Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference - E-Book. Elsevier Health Sciences. 2019..
[vii] Merck Manual Professional Version. Iron Deficiency Anemia. Reviewed/Revised Jun 2023 https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia
[viii] Quest Diagnostics. Iron Studies.
