Ferritin (serum Ferritin Level)

Sample

1. This test is done on a serum that is stable for 7 days at 2 to 8 °C.
2. This can be stored at -20 °C for 6 months.

Precautions

1. Avoid violent mixing which will denature the ferritin.
2. Avoid freezing and thawing of the sample.
3. Screening test for early detection of iron overload, ferritin is not a good indicator than measurement of serum iron, TIBC, and transferrin saturation.

Indication

1. This is the most sensitive test for the diagnosis of iron-deficiency anemia.
2. This test is advised to see the iron stores in the body.

Pathophysiology

1. Iron in the diet is absorbed (5 to 10%)  by the intestinal epithelial cells (mainly duodenum and upper jejunum)  and then it goes into the blood and utilized by the RBCs in the bone marrow.
   1. Non-pregnant women’s iron minimum daily requirement is 1 mg.
   2. Pregnant and lactating women are >1 mg of iron.
   3. During the 2nd and 3rd trimester daily requirement of iron is 5 to 6 mg.
   4. 1000 calories of the diet contain 6 mg of iron.
   5. 2500 calories consumed by the adult will contain15 mg of iron/day in the ingested diet.
2. Iron exists in different forms in the blood and tissue.
   1. Dietary iron is in ferrous (Fe²⁺) and ferric (Fe³⁺) form.
   2. In Hemoglobin, it is in the Fe2⁺ form.
   3. Transferrin has a ferric (Fe³⁺) form and is present in the serum.
   4. Ferritin has a ferric (Fe³⁺) form and is present in the serum and tissues.
   5. Hemosiderin has a ferric (Fe³⁺) form and is present in the bone marrow and tissue.

3. Iron form transferrin and iron combine with Hb and RBCs get mature.
   1. RBCs enter the circulation and after around 4 months are taken up by the phagocytic cells.
   2. Iron is released by the phagocytic cells into plasma and forms transferrin.

4. To understand the ferritin, we have to have an idea about the Transferrin.
   1. Apotransferrin is β1-globulin with attached two molecules of iron, Fe+++ is called Transferrin.

5. Ferritin consists of:
   1. Ferritin consists of an apoferritin shell that has 24 subunits and a crystalline core which has iron in the form of FeOOH (ferric oxyhydroxide).
   2. Ferritin is the primary storage compound for iron, found in the liver, spleen and bone marrow, gastrointestinal mucosa, and reticuloendothelial system.

5. 3. It is easily mobilized for utilization by the body.
   4. It is an indirect measure of the iron store.
   5. Hemosiderin is the aggregates of ferritin. Iron is released slowly from the hemosiderin for the utilization by the body as compared to ferritin.

6. Ferritin structure:
   1. is the complex of ferric hydroxide and protein, apoferritin, these are formed in the reticuloendothelial system.
   2. Ferritin = Ferric oxyhydroxide + Apoferritin
7. Ferritin has the shape of a hollow sphere that permits the entry of a variable amount of iron for storage (as ferric hydroxide phosphate complexes).
8. Iron uptake by ferritin requires prior oxidation of Fe++ (ferrous) to Fe+++ (ferric). This takes place in the stomach by the HCL acid.

9. When the body iron store is high then ferritin of mucosal epithelial cells is high and transferrin will below.
10. Ferritin is present in the blood in very low concentration.
    1. Normally ∼ 1% of the plasma iron is present in the form of ferritin.
    2. During the menstrual cycle, 40 to 80 mL of blood is lost, and 20 to 40 mg of iron.
    3. Plasma ferritin concentration declines very early in the development of iron deficiency before changes in the hemoglobin appear.
11. Ferritin is the major storage protein of the iron.
    1. The ferritin stored in the men is roughly 800 mg.
    2. In healthy female is 0 to 200 mg.
    3. 1 ng/ml of ferritin is equivalent to 8 mg of iron stores.
12. Iron loss in urine and sweat is <1 mg/day.
    1. Intestine regulates iron absorption.
    2. Transferrin is in excess in plasma but only 30% is saturated by iron.

13. Ferritin contains 20 to 25 % iron.
    1. Its concentration is a good measure of iron stores in a normal person. and in iron deficiency.
    2. In conditions of iron overload and in some chronic diseases, serum ferritin is not a reliable estimate of iron stores.
14. Ferritin level rises persistently in the male and postmenopausal women.
15. The decrease in the ferritin level indicates iron storage decreases and iron deficiency anemia.
16. Pregnancy is associated with decreased ferritin levels.
17. Increased ferritin indicates hemochromatosis, hemosiderosis, iron poisoning, and recent blood transfusion.
    1. There may be an increased ferritin level in megaloblastic anemia, hemolytic anemia, and chronic hepatitis.
18. Ferritin act as acute-phase protein so maybe elevated which do not indicate iron storage like acute inflammatory diseases, infections, metastatic cancers, and lymphomas.
19. When Ferritin is combined with serum iron level and total iron-binding capacity (TIBC), it is used to differentiate different types of anemias.
20. Ferritin level is more specific than iron concentration or TIBC for the diagnosis of iron deficiency.
21. Ferritin decreases before anemia or other changes appear.

Normal ferritin  

Source 1

• Children = 7 to 140 ng/ml.
  • Newborn = 25 to 200 ng/ml
  • One month  = 200 to 600 ng /mL.
  • 2 to 5 months  = 50 to 200 ng /mL.
  • 6 months to 15 years    = 7 to 142 ng/mL.
• Adult male = 20 to 250 ng/ml
• Adult Female = 10 to 120 ng/ml
• Iron overload = >220 ng/ml
• In men With anemia of chronic diseases is = <100 ng/ml
• In women with anemia of chronic diseases is = <20 ng/ml.
• <10 ng/mL is diagnostic of iron deficiency anemia.

Source 2

•  Male = 12 to 300 ng/mL (12 to 300 µg/L)
• Female = 10 to 150 ng/mL  (10 to 150 µg/L)
• Children
  • Newborn = 25 to 200ng/mL
  • 0ne month = 200 to 600 ng/mL
  • 2 to 5 months = 50 to 200 ng/mL
  • 6 months to 15 years = 7 to 142 ng/mL

The increased Ferritin level is seen in:

1. Ferritin levels may increase with age in males and in postmenopausal females.
2. A marked increase was seen in iron overload e.g Hemochromatosis, and certain liver diseases.
3. Slightly increased seen in acute leukemia.
4. Inflammatory diseases like pulmonary infections, osteomyelitis, chronic UTI.
5. Rheumatoid arthritis, SLE.
6. Certain chronic liver diseases.
7. Acute myeloblastic, and Lymphoblastic leukemia.
8. Hodgkin’s lymphoma and breast cancers.
9. It may be seen in viral hepatitis or following toxic injury to the liver. In that case, ferritin is released from the damaged liver cells.

The decreased Ferritin level is seen in:

1. Iron deficiency anemia when ferritin level is <10 ng/ml.
2. Heavy menstrual bleeding.
3. Persistent bleeding of GIT.
4. Poor absorption by the GIT.

Table showing various types of anemia and lab workup:

Disease	Ferritin	Transferrin sat.	Iron	TIBC
Acute blood loss	normal	Low	low	normal
Chronic blood loss	low	low	low	increased
Hemolytic anemia	increased	increased	increased	low
Iron deficiency	low	low	low	increased
Pregnancy	low	low	low	increased
Acute inflammation	increased	increased	normal	low
Hemochromatosis	increased	increased	increased	low
Chronic diseases	increased	low	low	low
Liver diseases (necrosis)	increased	increased	increased	increased

TIBC = total iron-binding capacity.
Transferrin sat. = Transferrin saturation.

 

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