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Chairman: Peter Jatlow, MD
Editor: Henry M. Rinder, MD
Production Assistant: June D. Fisher
Contributors:Pei Lin, M.D., J. Greg Howe, Ph.D., Marie Louise Landry, M.D., Howard P. Flitman, M.D., Stephen E. Edberg, Ph.D., Peter McPhedran, M.D.

TRANSFERRIN RECEPTOR FOR IRON DEFICIENCY ANEMIA

   Iron deficiency anemia (IDA) is one of the most common causes of anemia worldwide. Although the diagnosis of IDA is frequently made casually, iron pills are easy to take and usually well tolerated; making an accurate diagnosis is important since IDA in adults requires a search for the source of blood loss. In men and post-menopausal women, endoscopy from below and above is usually done. Menstruating women who have iron deficiency are usually assumed to have become deficient due to menstrual blood loss. However, they should still have stools checked for occult blood to rule out a gastro-intestinal source of blood and iron loss. Many laboratory tests and other forms of clinical evaluation are available for the diagnosis of IDA, but each has its limitation(s).

Table 1
Tests used in diagnosing iron deficiency anemia (IDA)
Test Limitations
*Blood smear hypochromia Subjectivity
*MCV Insensitivity
RDW Non-specificity
Serum iron Markedly lowered by fever or inflammation
Iron binding capacity (IBC) Moderately lowered by fever; increased by pregnancy
Iron/IBC (% saturation) Like serum iron, lowered by fever
*Ferritin Mildly raised by fever or inflammation
Stool for occult blood Bleeding may be intermittent
Endoscopy: EGD and colonoscopy Expensive and invasive; appropriate after iron deficiency is diagnosed
Bone marrow for iron stores Expensive and invasive; iron depletion does not prove IDA
Treatment with oral iron, followed by hemoglobin and hematocrit surveillance (1 month) Effect is slow; H/H may rise for other reasons
*probably the best tests, currently


   The most commonly relied upon tests are serum iron, iron/IBC or "% saturation", and ferritin. Both serum iron and "% saturation" are dramatically lowered by fever or inflammation and frequently suggest iron deficiency in patients who actually have anemia of inflammatory disease. Serum ferritin is less affected by inflammation, but tends to rise into the low normal range when a truly iron deficient person develops fever (thus a baseline ferritin of 10 in an iron deficient person may go to 20 when fever supervenes). If some of the other indicators of iron deficiency, such as hypochromia and microcytosis, are present in a patient with anemia, fever, and a ferritin of 20-25, the diagnosis of iron deficiency is relatively easy. However, bone marrow examination may still occasionally be needed to make the distinction between iron deficiency and anemia of inflammatory disease.

    Iron used in the formation of heme is transported from the gastro-intestinal tract and the reticulo-endothelial system to red cell precursors by the iron binding protein transferrin, the major component of plasma iron binding capacity. Red cell precursors are equipped, to a greater degree than other body cells, with transferrin receptors in order to pass iron from transferrin into the cytosol. Pieces of some of these receptors break off and circulate in plasma, and there is an equilibirium between receptors on cell surfaces and those in plasma. In iron deficiency, erythroid precursors express more receptors, and more receptor fragments circulate in blood. "Soluble", or "serum", transferrin receptors (sTfR) are increased in the presence of iron deficiency (>45 nM/L), but are not increased in anemia of chronic disease or inflammation. Elevated sTfR are, however, also seen in patients with erythroid hyperplasia due to chronic hemolytic anemias such as sickle cell disease and auto-immune hemolytic anemia.

    The transferrin receptor test is performed on serum (red top tube) by an ELISA method. It will be performed at least every other week in the Hematology lab (8-2434). Reference ranges:

Published reference range for test
(95% confidence limits)
8.8-28.1 nM/L
Range determined in YNHH Lab ("official")
(100% range of 40 normals)
5.0-34.5 nM/L

The sTfR test should be considered for anemic patients whose differential diagnosis includes iron deficiency and anemia of inflammatory disease. Transferrin receptor values are elevated in IDA, and in chronic hemolytic anemias.

Testing Algorithm

References
  1. Ferguson BJ et al. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab and Clin Med 1992; 119:385-390.
  2. Cook JD et al. Serum transferrin receptor. Ann Rev Med 1993; 44:63-74.
  3. Punnonen K et al. Iron deficiency anemia is associated with high concentrations of transferrin receptor in serum. Clin Chem 1994; 40:774-776.

Peter McPhedran, M.D.
 

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