Total Iron Binding Capacity (TIBC): Iron storage in different sites

Iron metabolism: Total Iron Binding Capacity (TIBC)

Iron metabolism and absorption

Total Iron Binding Capacity (TIBC)

What sample is needed for Total Iron Binding Capacity (TIBC)?

1. Take blood (3 to 5 mL) to prepare the serum.
2. The early morning sample is preferred because of the diurnal variation in the iron concentration.
3. Take the sample in the morning (around 10 am) because the iron level varies daily.
4. The specimen may be collected as serum without anticoagulant.
5. Can use plasma with heparin.
6. Reject the hemolysed sample.

What are the Precautions for Total Iron Binding Capacity (TIBC)?

1. Do not use anticoagulants like oxalate, citrate, or EDTA because these bind to iron and are unacceptable.
2. Twelve hours of fasting is preferred.
3. Water intake is allowed.
4. Stop taking iron-containing supplements before 24 to 48 hours.
5. Chloramphenicol and oral contraceptives can raise the TIBC value.
6. Adrenocorticotrophic hormones can produce false negative results.
7. If you handle blood samples roughly, it leads to invalidated results.
8. Avoid vitamin C, which increases iron absorption. Foods rich in vitamin C include oranges, grapefruit, cabbage, and potatoes.

What are the Indications for Total Iron Binding Capacity (TIBC)?

1. This is done to diagnose the anemias. It helps in the differential diagnosis of anemia.
2. Other tests needed are Total iron and Transferrin.
3. This helps in iron metabolism.
4. It is used to screen for iron overload.
5. TIBC evaluates:
   1. Amount of iron.
   2. Iron storage.
   3. Nutritional status in anemia.

How will you define Total iron binding capacity (TIBC)?

1. TIBC is calculated as follows:
   1. Transferrin (mg/L) x 0.025 = µmol/L.
2. TIBC measures the maximum amount of iron bound to protein and transports iron in the blood.
3. The maximum amount is transferred as transferrin.
4. It is the capacity of transferrin to bind to iron.
5. TIBC is an indirect measurement of Transferrin concentration.
   1. TIBC measures the total amount of iron that apotransferrin has the capacity to bind.

What is the pathophysiology of Total Iron Binding Capacity (TIBC)?

1. TIBC refers to the amount of iron that could be bound by saturation of transferrin and other minor iron-binding proteins in the serum or plasma.
2. TIBC is the sum of all proteins bound to iron.
3. TIBC increases by 70% in patients with iron deficiency anemia.
4. When serum iron falls, then TIBC increases.
5. TIBC is increased in the presence of iron deficiency but may be normal or low in chronic diseases.
6. TIBC may be calculated from the direct measurement of serum transferrin by the following formula:
   1. TIBC µg/dL = serum transferrin mg/dL x 1.25²¹ ( Another reference = Transferrin mg/dL x 0.025).
   2. A small proportion of the iron is bound to other proteins, so the above equation underestimates the TIBC.
7. The amount of apotransferrin still available to bind the iron can be measured in the unsaturated iron-binding capacity.
   1. 1. It is measured as = TIBC minus serum iron (µg/dL).

Ferritin:

What sample is needed for the Ferritin level?

• Venous blood is needed to prepare the serum.

What are the indications for Ferritin level?

1. It differentiates and classifies anemias.
2. It measures the amount of iron storage protein.
3. It diagnoses iron deficiency or excess.
4. It predicts and monitors iron deficiency.
5. It tells the response to iron therapy.
6. It differentiates iron deficiency from chronic diseases as a cause of anemia.
7. It monitors iron status in patients with chronic renal diseases with or without dialysis.
8. It can be used as a population study for iron levels and response to the iron supplement.

What are the precautions for Ferritin?

1. Record the age of the patient. Old people have less Ferritin level.
2. It is lower in the menstruating women than in the premenopausal age.

How will you define Ferritin?

1. It is the chief iron-storage protein in the body.
2. It represents stored iron.

How will you interpret Ferritin?

1. 10% to 20% – 30% of the total iron is stored as Ferritin.
2. Iron is stored as ferritin in the body in the liver, spleen, and bone marrow.
3. Or stored as Ferric (Fe ⁺⁺⁺) bound to an apoferritin protein molecule.
4. When iron is needed, it is released from the Ferritin and bound to the β₁ globulin molecule, transferrin.
5. Serum Ferritin is the best diagnostic test for iron deficiency anemia.
   1. Because ferritin is the measure of the iron stored in the body.
6. In iron deficiency anemia, the ferritin level is <15 µg/L as compared to the normal level of 20 to 250 µg/L.
7. In children <, 6 µg/L  compared to the normal value of 7 to140 µg/L.
8. In baby <, 12 µg/L compared to the normal values of 50 to 200 µg/L.
9. Ferritin is the acute phase protein, so its value may increase in infections, SLE, liver diseases, malignancies, and chronic renal failure.

Transferrin:

What sample is needed for Transferrin estimation?

• Collect venous blood to prepare the serum.

What are the indications for Transferrin?

1. Transferrin measures iron absorbed from diet sources.
2. Transferrin measures iron produced by the breakdown of RBCs.

What are the precautions for Transferrin estimation?

1. With estrogen and oral contraceptive therapy, Transferrin levels increase.
2. Transferrin level decreases with dextran, corticotropin, corticosteroids, testosterone, and asparaginase.
3. Hemolysis may affect the test result.
4. Foods like liver, egg yolk, beef, and prune juices are rich in iron.
5. Avoid vitamin C-rich foods like grapefruits, oranges, potatoes, and cabbage.

How will you define transferrin?

1. Transferrin is a glycoprotein and is responsible for the transport of iron.
2. Transferrin transport circulating Fe⁺⁺⁺ molecule.
3. Normally, only 1/3 of the sites of iron bindings are occupied.
4. The remaining unoccupied sites are called unsaturated iron-binding capacity.
5. Transferrin transports iron throughout the body and carries it to the cells.
6. A low level of transferrin will lead to inadequate formation of hemoglobin and results in anemia.

How will you interpret the Transferrin?

1. It represents the major protein that binds to iron. The majority of the iron is bound to transferrin.
2. Transferrin is a beta-globulin (β1-globulin).
3. Transferrin’s capacity to bind iron in normal plasma is 240 to 360 µg/dL.
4. Transferrin also acts as an acute-phase protein.
5. This is a transport protein synthesized in the liver.
6. This regulates iron absorption.
7. Transferrin is also called siderophilin.
   1. Total iron + TIBC + Transferrin, when done together, helps in the differential diagnosis of anemia.
8. The cellular uptake of iron is mediated by the cell surface transferrin receptor (TR).
   1. The number of transferrin receptors depends upon the cell’s need for iron.
   2. In the case of apoferritin deficiency, an excess of iron is deposited as small granules of Iron Oxide called hemosiderin.

What are the Transferrin functions?

1. Help in the production of hemoglobin.
2. Helps to regulate the amount of iron in the body.
3. It binds to iron and prevents damage to the cells and tissues.
4. Transferrin measurement shows the body’s ability to transport and regulate iron.

Transferrin saturation:

What sample is needed for the Transferrin saturation test?

• Take venous blood to prepare the serum.

What are the indications for the Transferrin saturation test?

1. It is advised for the differential diagnosis of anemia.
2. It helps in iron deficiency anemia.
3. It helps in the evaluation of Thalassemia, sideroblastic anemia, and hemochromatosis.
4. It differentiates hereditary hemochromatosis.

What are the precautions for the Transferrin saturation test?

1. Avoid hemolysis that will interfere with the result.
2. Some drugs will affect the result.
3. Iron contamination of the gloves used in the test will give high values.

How will you define Transferrin saturation?

1. Serum transferrin situation is obtained by dividing serum iron by TIBC.
2. It is normally 20% to 50%.
3. It represents the amount of iron-binding sites that are occupied.

How will you interpret Transferrin saturation?

1. It is the percentage of transferrin and other iron-binding proteins.
2. Transferrin saturation is calculated as follows.
   1. Transferrin saturation (%) = serum iron level (µg/dL) / TIBC (µg/dL) x 100
   2. The normal value for transferrin saturation is 20% to 50%.
   3. This may vary with age and sex.
3. Transferrin saturation helps find the cause of abnormal iron and TIBC levels.
   1. Transferrin saturation is below 15% in a patient with iron deficiency anemia.
4. Transferrin saturation is increased in patients:
   1. Hemolytic anemia.
   2. Sideroblastic anemia.
   3. Megaloblastic anemia.
   4. Patient with iron overload or iron poisoning.
   5. Hemochromatosis.

What is the clinical importance of Transferrin saturation?

1. This test is crucial in evaluating abnormal iron and TIBC levels.
2. It provides insights into iron metabolism and assists in diagnosing and monitoring disorders of iron homeostasis.

What is normal TIBC, Transferrin, and Transferrin saturation?

Source 1

Transferrin

• To convert into SI units x 0.01 = g/L

Total Iron binding capacity (TIBC)

• Adult = 250 to 425 µg/dL

Iron saturation (%Transferrin saturation)

• Male = 20% to 50%
• Female = 15% to 50%
  • To convert into SI units x 0.01 = Fraction saturation

Source 2

TIBC 

1. 250 to 400 µg/dL.
2. It decreases in older people at around = 250 µg/dL.
   • (This value varies from one reference to another)

Transferrin

1. Adult = 250 to 425 mg/dL.
2. Children = 203 to 360 mg/dL.
3. Newborn = 130 to 275 mg /dL.

Transferrin saturation

1. Male = 20% to 50 %.
2. Female = 15% to 50 %.

Ferritin 

1. Adult male = 12 to 300 ng/mL (12 to 300 µg/L).
2. Adult female = 10 to 150 ng/mL (10 to 150  µg/L).
3. Children
   1. Newborn = 25 to 200 ng/mL.
   2. One-month-old = 200 to 600 ng/mL.
   3. 2 to 5 months old = 50 to 200 ng/mL.
   4. 6 months = 7 to 142 ng/mL.

What is the cause of decreased Ferritin levels?

• Iron-deficiency anemia.

What are the causes of increased Ferritin levels?

1. Ferritin is an acute-phase protein raised in chronic liver diseases, alcoholism, malignancies, infection, and inflammation.
2. In hemosiderosis.
3. In idiopathic hemochromatosis.
4. Anemias other than iron deficiency.
5. Renal cell carcinoma due to hemorrhage in the tumor.
6. End-stage renal diseases.
7. It increases with age.

What are the causes of increased TIBC?

1. Pregnancy.
2. Iron deficiency.
3. Acute hepatitis.
4. Acute and chronic blood loss.

What are the causes of the decreased TIBC?

1. Hemochromatosis.
2. Hypoproteinemia in malabsorption.
3. Burns.
4. Cirrhosis.
5. Renal diseases like nephrosis, etc.
6. Thalassemia.
7. Hyperthyroidism.
8. Chronic diseases.
9. Non-iron deficiency anemia

What are the causes of increased Transferrin?

1. Iron deficiency anemia.
2. Pregnancy.
3. Estrogen therapy.
4. Hyperestrogenism.

What are the causes of decreased Transferrin?

1. Chronic infections.
2. Acute inflammation.
3. Microcytic anemia due to chronic diseases.
4. Protein deficiency in malabsorption and burns.
5. Liver disease, acute.
6. Renal disease like nephrosis.
7. Hemochromatosis.
8. Genetic deficiency of transferrin.

What are the causes of increased Transferrin saturation?

1. Hemochromatosis.
2. Thalassemia.
3. Hemosiderosis.
4. Ingestion of iron.
5. Birth control pills.
6. Iron dextran injection.

What are the causes of decreased Transferrin saturation?

1. Iron deficiency anemia.
2. Anemia of infections and chronic diseases.
3. Uremia.
4. In some of the malignancies.
5. Rheumatoid arthritis.

What are the findings of Differential diagnosis of various diseases?

Questions and answers:

• Please see more details in Total Iron.