Iron deficiency anemia diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [3]

Overview

Iron deficiency anemia is diagnosed on the baisis of results of CBC, peripheral blood film and iron studies.

Diagnostic Study of Choice

Study of choice

  • Iron stain (Prussian blue stain) of bone marrow macrophages and erythroid precursors (sideroblasts) on marrow spicules is the gold standard test for the diagnosis of iron deficiency anemia[1]
  • Serum ferritin is the most widely used test for the diagnosis of iron deficiency anemia as it is non invasive. However, ferritin also acts as an acute phase reactant and can be unreliable in inflammatory illness. Iron studies are performed to look for the cause of iron deficiency.
  • Iron deficency studies are performed if anemia is found on CBC and microcytic or normocytic anemia found on peripheral blood film.
Diagnostic results

The findings of various test results that confirm iron deficiency are[2][3][4][5][6][7][1]

  • Iron stain (prussian blue staining) of erythroid precursors (sideroblasts) on marrow spicules shows ack of stainable iron in erythroid precursors.
  • Serum ferittin levels < 30ng/ml, and serum ferritin <41 ng/mL in a patient with anemia and comorbidities (chronic diseases/inflammation)
  • Serum iron <60 mcg/dL.
  • Total iron binding capacity/ serum transferrin- TIBC is calculated by multiplying serum transferrin by 1.389. It is increased in iron deficiency anemia and decreased in anemia of chronic disease. TIBC>350 to 400 mcg/dL is diagnostic of iron deficiency.
  • Transferrin saturation (TSAT) is the ratio of serum iron to TIBC: (serum iron  ÷  TIBC  x  100). It is <15% in iron deficiency (normal is 25-40%).
  • Elevated erythrocyte (RBC) zinc protoporphyrin (eg, >80 mcg/dL).
  • Decreased iron stain on eryhtroid precursors.
Sequence of Diagnostic Studies

The various investigations must be performed in the following order:

  • Complete blood count
  • Peripheral blood film
  • Iron studies:
    • Serum ferritin
    • Serum iron
    • Serum transferrin/ total iron binding capacity
    • Transferrin saturation
  • Serum eryrthrocyte zinc protoporphyrin
  • Iron stain (prussian blue stain) on bone marrow aspirate

Diagnostic Criteria

 
 
 
 
 
 
 
 
Hb<10 mg/dl, MCV <95fL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum ferritin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ferritin <30mg/ml
 
 
 
 
Ferritin 31-99mg/ml
 
 
 
 
Ferritin >100mg/ml
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• TIBC >350mcg/dl
OR
• Serum iron <60mcg/dl
OR
• Transferrin saturation <15%
 
• TIBC-300-350mcg/dl
OR
• Serum iron-60 to 150 mcg/dL
OR
• Transferrin saturation 25-40%
 
• TIBC <300mcg/dl
OR
• Serum iron >150mcg/dl
OR
• Transferrin saturation >40%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythrocyte zinc protoporphyrin >100ng/ml RBC
 
Erythrocyte zinc protoporphyrin-30-70ng/ml
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increased iron staining on erythroid precursors
 
Decreased/Normal iron staining on erythroid precursors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Iron deficiency anemia
 
 
 
 
 
 
Evaluate for other causes of anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

References

  1. 1.0 1.1 Price EA, Mehra R, Holmes TH, Schrier SL (2011). "Anemia in older persons: etiology and evaluation". Blood Cells Mol Dis. 46 (2): 159–65. doi:10.1016/j.bcmd.2010.11.004. PMID 21208814.
  2. Camaschella C (2015). "Iron deficiency: new insights into diagnosis and treatment". Hematology Am Soc Hematol Educ Program. 2015: 8–13. doi:10.1182/asheducation-2015.1.8. PMID 26637694.
  3. Unsworth DJ, Lock RJ, Harvey RF (2000). "Improving the diagnosis of coeliac disease in anaemic women". Br J Haematol. 111 (3): 898–901. PMID 11122153.
  4. Rector WG (1989). "Pica: its frequency and significance in patients with iron-deficiency anemia due to chronic gastrointestinal blood loss". J Gen Intern Med. 4 (6): 512–3. PMID 2585159.
  5. Khadem G, Scott IA, Klein K (2012). "Evaluation of iron deficiency anaemia in tertiary hospital settings: room for improvement?". Intern Med J. 42 (6): 658–64. doi:10.1111/j.1445-5994.2012.02724.x. PMID 22288902.
  6. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016). "Iron deficiency anaemia". Lancet. 387 (10021): 907–16. doi:10.1016/S0140-6736(15)60865-0. PMID 26314490.
  7. Cook JD, Skikne BS (1989). "Iron deficiency: definition and diagnosis". J Intern Med. 226 (5): 349–55. PMID 2681511.

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