Iron

The amount of circulating iron bound to transferrin is reflected by the serum iron level.

The serum iron reference ranges are as follows ^[1] :

• Male: 80-180 mcg/dL or 14-32 μmol/L (SI units)
• Female: 60-160 mcg/dL or 11-29 μmol/L (SI units)
• Newborn: 100-250 mcg/dL
• Child: 50-120 mcg/dL

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

Description

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]

Indications/Applications

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]

Considerations

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]