Iron deficiency anemia

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Iron deficiency anemia
Redbloodcells.jpg

Red blood cells
ICD-10 ICD10 F84.0-F84.1
ICD-9 280
MeSH D018798

Iron deficiency anemia is the most common type of anemia, and the most common cause of microcytic anemia.

Iron deficiency anemia occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed. In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during menses.

Iron deficiency anemia is the final stage of iron deficiency. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use in the bone marrow, liver, and spleen. Iron deficiency ranges from iron depletion, which yields little physiological damage, to iron deficiency anemia, which can affect the function of numerous organ systems. Iron depletion causes the amount of stored iron to be reduced, but has no effect on the functional iron. However, a person with no stored iron has no reserves to use if the body requires more iron. In essence, the amount of iron absorbed by the body is not adequate for growth and development or to replace the amount lost.

History

A disease believed to be iron deficiency anemia is described in about 1500 B.C. in the Egyptian Ebers papyrus. It was termed chlorosis or green sickness in Medieval Europe, and iron salts were used for treatment in France by the mid-17th century. Thomas Sydenham recommended iron salts as treatment for chlorosis, but treatment with iron was controversial until the 20th century, when its mechanism of action was more fully elucidated.

Symptoms

Iron deficiency anemia is characterized by pallor, fatigue and weakness. Because it tends to develop slowly, adaptation occurs and the disease often goes unrecognized for some time. In severe cases, dyspnea can occur. Unusual obsessive food cravings, known as pica, may develop.

Other symtpoms include:

  • Cognitive dysfunction[1]

One of the first abnormal values to be noted on a CBC will be a high red blood cell distribution width (RDW), reflecting a varied population of red blood cells. A low MCV, MCH or MCHC, and the appearance of the RBCs on visual examination of a peripheral blood smear will narrow the diagnosis to a microcytic anemia.

Mean corpuscular volume (MCV) for the predicting a ferritin < 15 ng/ml[2]
MCV Sensitivity Specificity
< 70 fL 24% 96%
< 80 fL 48% 83%
< 92 fL 88% 39%

Evaluation of iron status

The serum ferritin is the best laboratory test for storage of marrow iron.[3][4][5] Other test that have been used are serum iron level, and serum transferrin level. While serum iron varies greatly intra-individually also in response to iron intake, the other two parameters mentioned change in an acute phase reaction (ferritin rises and transferrin false) and thus cannot reliably detect iron deficiency in the presence of inflammation. They also do not measure if the iron is actually available for hematopoiesis. Modern tests that circumvent this problem include soluble transferrin receptor (sTfr), transferrin saturation (TfS or TSAT), the hemoglobin content of reticulocytes or the percentage of hypochromic cells [6]. Most of these can today be readily determined on automated laboratory analysis systems.

Likelihood ratios for common tests[7]
Test Cutoff value Likelihood ratio
MCV ≥ 90 m3 0.29
MCV ≤ 70 m3 12.47
RDW ≤ 15% 0.61
RDW ≥ 21% 2.72
Ferritin ≥ 100 ng/ml 0.08
Ferritin < 25 ng/ml < 8.83
Transferrin saturation ≥ 50% 0.15
Transferrin saturation ≤ 5% 10.46
A likelihood ratio > 10 helps establish a diagnosis while a ratio < 0.1 helps exclude a diagnosis.[8]

Iron deficiency is difficult to diagnose in alcoholics.[9]

Diagnosing iron deficiency in alcoholics.[9]
Finding Cutoff value Sensitivity Specificity
MCV < 80 m3 25% 97%
Ferritin < 20 ng/ml 50% 100%
Transferrin saturation ≤ 15% 56% 87%
Ferritin < 20 ng/ml 50% 100%
Ferritin < 100 ng/ml 100% 95%

Evaluation of underlying causes

The diagnosis of iron deficiency anemia requires further investigation as to its cause. In adults, 60% of patients with iron deficiency anemia may have underlying gastrointestinal disorders leading to chronic fecal blood loss.[10] Other gastrointestinal causes include malaborption and celiac disease. Additional causes are dietary insufficiency, menstruation, diversion of iron to fetal erythropoiesis during pregnancy, intravascular hemolysis and hemoglobinuria or other forms of chronic blood loss should all be considered.

Treatment

If the cause is dietary iron deficiency, iron supplements, usually with iron (II) sulfate or iron amino acid chelate, can correct the anemia. Chelated iron is ten to fifteen times more bioavailable per mg and has none of the side effects of iron sulfate's sulfur content. If malabsorption is present, it may be necessary to administer iron parenterally (e.g., as iron dextran). Parenteral iron other than in chelated form, however, is generally poorly tolerated.

The replacement dose of iron, at least in the elderly, may be as little as 15 mg per day of elemental iron [11].

Follow up evaluation with retesting of the hemoglobin (Hgb), hematocrit (Hct), and mean corpuscular volume (MCV) may help demonstrate whether the treatment has been effective. Testing of the reticulocyte count is another way to measure a response to iron therapy. Finally, ongoing testing of iron indices via the ferritin level and maybe TIBC, and serum iron levels are imperative to avoid iron overloading.

Iron supplements must be kept out of the reach of children, as iron-containing supplements are a frequent cause of poisoning in the pediatric age group.

References

  1. Murray-Kolb LE, Beard JL (2007). "Iron treatment normalizes cognitive functioning in young women". Am. J. Clin. Nutr. 85 (3): 778–87. PMID 17344500[e]
  2. Seward SJ, Safran C, Marton KI, Robinson SH (1990). "Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia?". J Gen Intern Med 5 (3): 187–91. PMID 2187961[e]
  3. 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]
  4. 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.
  5. 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
  6. Thomas C, Thomas L (2002). "Biochemical Markers and Hematologic Indices in the Diagnosis of Functional Iron Deficiency". Clin Chem 48 (7): 1066-76. PMID 12089176.
  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. 9.0 9.1 Savage D, Lindenbaum J (September 1986). "Anemia in alcoholics". Medicine (Baltimore) 65 (5): 322–38. PMID 3747828[e]
  10. Rockey D, Cello J (1993). "Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia". N Engl J Med 329 (23): 1691-5. PMID 8179652.
  11. Rimon E, Kagansky N, Kagansky M, Mechnick L, Mashiah T, Namir M, Levy S (2005). "Are we giving too much iron? Low-dose iron therapy is effective in octogenarians". Am J Med 118 (10): 1142-7. DOI:10.1016/j.amjmed.2005.01.065. PMID 16194646. Research Blogging.

See Also

External links