Ferritin

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Ferritin is a water-soluble complex of protein and iron, which circulates in free form in the blood and can be measured in simple samples of serum or plasma. It is a cytosolic molecule comprised of subunits that self-assemble into a nanocage capable of containing up to 4500 iron atoms. [1]

Circulating ferritin is in equilibrium to ferritin molecules contained in histiocytes of the less easily measured bone marrow. In the histiocytes, the ferritin molecules accumulate into large cytoplasmic inclusions of hemosiderin, which is visible under the light microscope. Hemosiderin stains strongly with the Prussian Blue stain of marrow, and, if in sufficient concentration, is visible unstained.

Clinical use

Iron deficiency anemia

The serum ferritin is the best laboratory test for storage of marrow iron.[2][3][4] However, the accuracy of the ferritin has not been studied since the World Health Organization used a recombinant ferritin preparation to create a third, traceable International Standard in 1997.[5][6]

Likelihood ratios for common tests[7]
Test Cutoff value Likelihood ratio
Ferritin ≥ 100 ng/ml 0.08
Ferritin < 25 ng/ml < 8.83
A likelihood ratio > 10 helps establish a diagnosis while a ratio < 0.1 helps exclude a diagnosis.[8]

Iron overload

Other causes of high ferritin levels

Infections and neoplasms can elevate the ferritin over 1,000 ng/mL.[9]

References

  1. De Domenico, I et al. (2006), "Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome", EMBO Journal 25: 5396 - 5404, DOI:10.1038/sj.emboj.7601409
  2. Kis AM, Carnes M (July 1998). "Detecting iron deficiency in anemic patients with concomitant medical problems". J Gen Intern Med 13 (7): 455–61. PMID 9686711. PMC 1496985[e]
  3. Guyatt G, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R (1990). "Diagnosis of iron-deficiency anemia in the elderly.". Am J Med 88 (3): 205-9. PMID 2178409.
  4. Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C.Laboratory diagnosis of iron-deficiency anemia: an overview.J Gen Intern Med. 19927:145-53. Review. (Erratum in: J Gen Intern Med 1992;7:423) PMID: 1487761
  5. Thorpe SJ, Walker D, Arosio P, Heath A, Cook JD, Worwood M (1997). "International collaborative study to evaluate a recombinant L ferritin preparation as an International Standard.". Clin Chem 43 (9): 1582-7. PMID 9299937[e]
  6. Thorpe SJ (2010). "The development and role of international biological reference materials in the diagnosis of anaemia.". Biologicals 38 (4): 449-58. DOI:10.1016/j.biologicals.2010.02.007. PMID 20338782. Research Blogging.
  7. Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C (1992). "Laboratory diagnosis of iron-deficiency anemia: an overview". J Gen Intern Med 7 (2): 145–53. PMID 1487761[e]
  8. McGee S (August 2002). "Simplifying likelihood ratios". J Gen Intern Med 17 (8): 646–9. PMID 12213147[e]
  9. Lee MH, Means RT (1995). "Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance.". Am J Med 98 (6): 566-71. PMID 7778572[e]