Iron
Updated: Mar 09, 2022
Author: Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP, FAMIA; Chief Editor: Eric B Staros, MD
The amount of circulating iron bound to transferrin is reflected by the serum iron level.
The serum iron reference ranges are as follows[1] :
Increases in serum iron level are associated with the following:[2, 3, 4]
Idiopathic hemochromatosis
Liver necrosis (viral hepatitis)
Hemosiderosis caused by excessive iron intake (eg, multiple transfusions, excess iron administration)
Acute iron poisoning (children)
Hemolytic anemia
Pernicious anemia
Aplastic or hypoplastic anemia
Lead poisoning
Thalassemia
Vitamin B6 deficiency
Estrogens
Ethanol
Oral contraceptive
Decreases in the serum iron level are associated with the following:[2, 3, 4]
Iron deficiency anemia
Nephrotic syndrome(loss of iron-binding proteins)
Iron deficiency
Chronic renal failure
Many infections
Active hematopoiesis
Remission of pernicious anemia
Hypothyroidism
Malignancy (carcinoma)
Postoperative state
Kwashiorkor
Collection - Tiger-top or red-top tube
Panel - Iron panel
The metabolism of all living organisms requires iron. Iron is a part of heme, which is the active site of peroxidases that protect cells from oxidative injury by reducing peroxides to water. Heme is also the active site of electron transport in cytochromes.[4] When iron levels are insufficient, proliferation of bacteria or nucleated cells stops.[4]
Iron deficiency anemia may cause pallor, stomatitis, glossitis (smooth red tongue), angular cheilitis, and koilonychias. Patients with Plummer-Vinson syndrome may experience esophageal webs, dysphagia, and iron deficiency anemia.[5] Retinal hemorrhages and exudates may also be observed, especially in individuals with severe anemia. Although rare, splenomegaly in individuals with iron deficiency anemia likely results from other causes.[6, 4, 7]
The following is observed in patients with severe uncomplicated iron deficiency anemia
RBCs are hypochromic and microcytic.
The plasma iron concentration is decreased.
The iron-binding capacity is increased.
The serum ferritin concentration decreases.
The serum transferrin receptor and erythrocyte zinc protoporphyrin concentrations are increased.
The bone marrow is depleted of stainable iron.
The classic combination of these laboratory findings is observed only in severe and uncomplicated iron deficiency anemia that presents in patients without infection or malignancy who are not receiving blood transfusions or iron therapy.[4] Serum iron levels are often low in untreated iron deficiency anemia; however, levels may be normal.[8, 9]
If patients with iron deficiency anemia receive iron medication before blood is drawn, normal or high concentrations are typically noted. Even multivitamins with low (18 mg) elemental iron may produce this result. Thus, 24 hours before a blood draw for serum iron, all oral iron mediation should be stopped. Parenteral injection of iron dextran may result in high serum iron levels (eg, 500-1000 µg/dL) for several weeks.[10] Infusion of sodium ferric gluconate or iron sucrose causes increases in iron levels that last much shorter;[11, 12] these infusions are unlikely to interfere with serum iron testing.[11, 12, 4]
Deterministic factors for plasma iron concentration include the following:[4]
Absorption from the intestine
Storage in the intestine, liver, spleen, bone marrow
Rate of breakdown or loss of hemoglobin
Rate of synthesis of new hemoglobin
When screening for hereditary hemochromatosis, serum iron, iron-binding capacity, and transferrin saturation may be helpful.
Recent transfusions influence test findings.
The amount of circulating iron bound to transferrin is the serum iron level. The circulating transferrin is indirectly measured by the total iron-binding capacity (TIBC). Transferrin saturation in excess of 50% suggests a disproportionate amount of iron bound to transferrin is being delivered to nonerythroid tissues. If this continues for an extended time, tissue iron overload may be observed.[13]
Serum iron testing is indicated for the following:
Diagnosis of blood loss
Differential diagnosis of anemia
Diagnosis of hemosiderosis and hemochromatosis
Evaluation of iron deficiency
Diagnosis of acute iron toxicity particularly in children
Evaluation of thalassemia and sideroblastic anemia
Monitoring the response to therapy of anemia[3]
Serum iron testing does not reliably determine iron deficiency or identify hemochromatosis or other iron overload states. TIBC, transferrin saturation percentage, and ferritin levels are recommended measurements in these settings. Oral contraceptives increase the iron level. Iron dextran elevates serum iron levels several weeks. Ingestion of even small amounts of iron may transiently increase serum iron levels. Patients undergoing iron chelation therapy (deferoxamine) may have inaccurate serum iron test results.
Diurnal variation is observed with serum iron testing; normal values are found in the mid-morning, low values are found in mid-afternoon, and even lower values are found near midnight. Diurnal variation disappears at values below 45 µg/dL.[3]
A study by van der Staaij et al indicated that the ratio of transferrin saturation to hepcidin can be used to distinguish TMPRSS6-related iron refractory iron deficiency anemia from iron deficiency anemia arising from other causes, if inflammation is low or absent and no recent iron therapy has been administered. The investigators found the median transferrin saturation/hepcidin ratio to be higher for patients with the iron refractory anemia than for the other iron deficiency anemia cases, the values being 0.6%/nM and 16.7%/nM, respectively.[14]