LAB
NEWS
January
1999 . . . . . . . . . . Vol. 39 No. 1
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.
References
- 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.
- Cook
JD et al. Serum transferrin receptor. Ann Rev Med 1993; 44:63-74.
- 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.  |