Reticulocyte Indices in the Assessment of Iron Availability
Andrea A. Bohn, DVM, PhD, DACVP (Clinical Pathology)
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort
Collins, CO
Introduction
Iron deficiency is relatively uncommon in veterinary medicine, especially in adult animals.
While in young, nursing animals iron deficiency is due to insufficient intake for the amount of
growth, in adult animals the most common cause is chronic blood loss, typically occult.1 The
thing that often alerts a clinician to suspect iron deficiency is a CBC, as there are specific
changes associated with iron deficiency. Unfortunately, a disease process may be present for
weeks to months before some of these changes are recognized. Now that reticulocyte indices are
more readily available, they should be monitored because they can more quickly reflect changes
in iron availability.
Iron Deficiency and the CBC
Finding a microcytic anemia should alert the clinician to consider iron deficiency, as there are
few other disease processes that are associated with microcytosis. Portal systemic liver shunt is
the main other differential. Only very rarely might a chronic inflammatory process result in
microcytosis. All of these differentials for microcytosis involve iron metabolism in the disease
process. Microcytosis occurs when there are extra mitotic events during erythropoiesis.
Erythrocyte precursors need to reach a critical concentration of hemoglobin before mitoses are
arrested and the formation of hemoglobin requires iron.
Besides microcytosis, other abnormalities that may be detected on a CBC in relation to iron
deficiency are hypochromasia (seen visually and as indicated by the MCHC) and erythrocyte
poikilocytosis, especially keratocytes and schistocytes.
Limitations
While the CBC is very useful in alerting a clinician to iron deficiency, by the time the changes
are significant enough to be flagged as abnormal the disease process has been going on for quite
some time. For microcytosis to occur (as detected by the MCV), there has to be enough turnover
of the erythrocyte population so that the newer, smaller cells are in a high enough proportion to
decrease the calculated average size of the erythrocytes below the reference interval for MCV.
This typically takes weeks to months.1 An increase in RDW may alert one of a shift in cell size
before the MCV becomes abnormal, but this value gives no indication of which way the sizes are
changing. RDW may, though, prompt examination of the erythrocyte scattergrams or histograms,
which could possibly detect a shift toward smaller cells before the MCV becomes abnormal.
Reticulocyte indices
The lifespan of erythrocytes is 70 days in cats and 120 days in dogs. RBC indices, then, use
measurements of cells from day 1 to months old. The lifespan of reticulocytes is about 2 days
before they become mature erythrocytes. Therefore, reticulocyte indices can reflect changes
within that population rapidly, as the whole population turns over every couple of days rather
than months. Because reticulocytes are the newest cells out in the peripheral blood, their
hemoglobin content better reflects the recent iron availability for erythropoiesis.2,3
In people, CHretic is thought to be the most sensitive indicator of iron deficiency. A few studies
have looked at MCVretic and CHretic in dogs and cats.4,5,6 These indices correlated with other
indications of iron deficiency in dogs and were shown to be sensitive in detecting iron deficiency.
Further evaluation of specificity is needed.
CHretic & MCVretic
If a decrease is seen in CHretic and/or MCVretic, this indicates that there is currently a lack of iron
availability for erythropoiesis. These animals should be evaluated for possible iron depletion as
well as, possibly, inflammation or other processes that can cause functional iron deficiency.
References
1. Harvey JW. Iron metabolism and its disorders. In: Kaneko JJ, Harvey JW, Bruss ML, editors.
Clinical Biochemistry of Domestic Animals. 6th edition. Burlington: Elsevier, Inc.; 2008. p.
259-285.
2. Urrechaga E, Borque L, Escanero JF. Erythrocyte and reticulocyte indices in the assessment
of erythropoiesis activity and iron availability. Int Lab Hematol 2013;35:144-9.
3. Mast AE, Blinder MA, Dietzen DJ. Reticulocyte hemoglobin content. Am J Hematol
2008;83:307-10.
4. Fry MM, Kirk CA. Reticulocyte indices in a canine model of nutritional iron deficiency. Vet
Clin Pathol 2006;35:172-81.
5. Steinberg JD, Olver CS. Hematologic and biochemical abnormalities indicating iron
deficiency are associated with decreased reticulocyte hemoglobin content (CHr) and
reticulocyte volume (rMCV) in dogs. Vet Clin Pathol 2005;34:23-7.
6. Prins M, van Leeuwen MW, Teske E. Stability and reproducibility of ADVIA 120-measured
red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte
haemoglobin content (CH(R)) in the diagnosis of iron deficiency. Tijdschr Diergeneeskd
2009;134:272-8.