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Narrative review article illustrates the use and limitations of serum feritin as a marker of iron stores and discusses iron status in equiolibrium and disequilibrium.

There are no details/explanation provided for inclusion of cited articles.

None mentioned.

Recruitment: Methods for article inclusion not described. 

Design:  Narrative Review.

Blinding used (if applicable):  Not applicbable.

Intervention (if applicable):  Not applicable.

Statistical Analysis:  Statistical analysis not performed.

 

 

Timing of Measurements:  not applicable

Dependent Variables:  not applicable

Independent Variables: not applicable 

Control Variables:  not applicable

Initial N:  35 references included.

Attrition (Final N):  35

Age:  not mentioned

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:   

Location: Worldwide studies

 

Other Findings

Where iron is in the body

1. There are 4 g of iron in the human body with 3 g of iron in the RBCs.

2. Tissue iron is stored predominately in the liver, spleen or bone marrow within reticuloendothelial cells and parenchymal cells.

3. Tissue iron may be found as hemosiderin that is relatively inert and insoluble and unreactive.

4. Iron is transported in the plasma bound to transferrin with a turnover rate of 10 to 20 times/d.

5.  Plasma iron represents less than 0.1% of total body iron.

6. Unbound plasma iron is rapidly cleared from the body.

Gauging iron: serum ferritin

1. Serum ferritin is a reliable marker of mobilizable (labile) iron stores under normal circumstances.

    a. there is a logarithmic distribution of serum ferritin in normal subjects with an average plasma ferritin of 100 µg/L in men and 33 µg/L in women.

    b. there is a close correlation between serum ferritin levels and liver iron concentrations.

2. Serum ferritin, however is a less reliable marker in refractory anemia and is variable in the same individual over time.

What serum ferritin is 

Comparison of tissue and serum ferritin

	Tissue	Serum
Function	iron shortage & disposal	unknown
iron content	high	low/absent
Produced	on free ribosomes	polyribosomes on endoplasmic reticulum
Glycosylation	no	yes

Regulation of serum ferritin levels

1. The level of ferritin in plasma represents the balance between its secretion and its clearance.

2. The rate of clearance of serum ferritin is very fast—the biologic half-life is ~10 minutes.

3. The rate of synthesis is likely to be the factor that determines plasma ferritin levels except in liver disease or possibly other conditions that reduce the clearance of serum ferritin.

4. Iron levels affect both transcription and translation of ferritin genes.

Pathophysiologic Processes and serum ferritin levels

1. There is no clear-cut relationship between serum ferritin and iron available for effective erythropoiesis.

2. Increase in serum ferritin may be due to supressed erythropoiesis. 

• When erythropoiesis is switched off or reduced because of inflammatory or neoplastic processes, iron that was in the RBC pool must be deposited in stores.
•  with erythropoietic block, for every 1 g/dL decrease in Hg, there is a 20 µg/L increase in serum ferritin.
• tissue ferritin can be released during cellular necrosis or damage.

3.  It is difficult to determine if ferritin levels measured in serum are elevated because of high serum ferritin levels or becasue of the release of tissue ferritin.

Ferritin as a marker

 

1. Ferritin has limitations as a marker for iron status.

    a. in equilibrium, ferritin relates well to iron stores, but not in disequilibrium.

    b. at 150 µg/L, serum ferritin has a sensitivity and specificity for iron adequacy of only 71% and 69% in hemodialysis patients.

    c. serum ferritin is a more useful gauge of iron status at lower values than higher values.

    d. <12 µg/L, there is absolute iron deficiency.

    e. >15 µg/L, there is probably enough iron stores to meet erythropoetic demands.

    f. >100 µg/L adequate for support hemoglobin synthesis in anemia secondary to chronic disease.

    g. 1,000 µg/L considered the upper limit however, many conditions can cause the value to be elevated.

Erythropoietin: a new twist

1. Erythropoiesis is a very dynamic process requiring 30 mg iron/d; doubling the process would require 60 mg iron/d.

2. Erythropoeitin (EPO) speeds up the process by as much as 2 fold.  Early studies showed a quick decrease in ferritin before Hg levels changed.

3. Iron supplementation is often necessary to meet the demand for RBC production when erythropoeitin is given.

4. Increased RBC destruction cases increased release of heme, which allows for more iron to be deposited in stores.  Therefore, the labile iron pool grows and the plasma ferritin levels are elevated.

It is difficult to interpret very high serum ferritin levels in patients with CRF receiving EPO. Clinicians should interpret high serum ferritin levels with caution because of all of the known factors that can contribute to high levels. It is best to balance concerns of iron overload with providing adequate iron supplementation to maintain erythropoiesis in erythropoietin-stimulated patients.

University/Hospital:	University Hospital of Wales (UK),
Not-for-profit	0 Foundation associated with industry:

Good review of iron metabolism and the effects of EPO on serum ferritin and hemoglobin.