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Original Article

Red Cell Distribution Width (RDW) in the Diagnosis of


Iron Deficiency with Microcytic Hypochromic Anemia
Roosy Aulakh,1 Inderpreet Sohi,1 Tejinder Singh,1 and Naveen Kakkar2
Departments of 1Pediatrics and 2Pathology, Christian Medical College and Hospital, Ludhiana, Punjab, India

ABSTRACT
Objective. To study the utility of red cell distribution width (RDW) in the diagnosis of iron deficiency among children with
microcytic hypochromic anemia.
Methods. 151 children (6 months-12 years) with microcytic (MCV<75 fl) anemia were classified into iron deficient (IDA) and
non-iron deficient anemia (non-IDA) on the basis of serum ferritin and total iron binding capacity (TIBC). RDW values were
obtained on an automated hematology analyzer. Receiver operator curves (ROC) were constructed and the utility of RDW in
diagnosis of iron deficiency was studied.
Results. The mean RDW value was 18.372.22% in IDA group (97 children) compared to 16.551.51 % in the non-IDA
group (54 children) (p<0.0001, unpaired t test). In IDA group, the mean RDW value was 16.601.78%, 17.951.91% and
20.551.32% among mild, moderate and severely anemic children (p<0.0001). The corresponding values in non-IDA group
were 16.031.25%, 16.761.20% and 16.772.68% respectively (p=0.269). At a cut-off value of 17.4%, as obtained from the
ROC curve, the sensitivity and specificity of RDW in diagnosis of IDA were 81.0% and 53.4% and a positive and negative
predictive value of 63.0% and 72.2% respectively. [Indian J Pediatr 2009; 76 (3) : 265-267] E-mail: drtejinder@rediffmail.com
Conclusion. RDW has a limited specificity for diagnosis of IDA among children with microcytic hypochromic anemia.
Key words: Red cell distribution width; Iron deficiency anemia; Microcytic hypochromic anemia

Iron deficiency anemia (IDA) is the most prevalent


micronutrient
deficiency
in
the
world 1 .
Morphologically, iron deficiency anemia is microcytic and
hypochromic as is beta-thalassemia trait (BTT) thereby
creating a confusion on peripheral blood smear
examination2. Beta-thalassemia is the most commonly
inherited hemoglobinopathy and often is presumptively
diagnosed as iron deficiency anemia when based only on
red blood cell (RBC) indices and morphologic features.
Differentiation of these microcytic anemias is of clinical
importance, particularly in a multi-ethnic Indian
population, because each has entirely different cause,
pathogenesis, prognosis and treatment. Thus an unknown
number of misdiagnosed thalassemias may be
unnecessarily treated with iron. The real danger of
misdiagnosis or non diagnosis in carriers of the thalassemia
trait, however, is a potential homozygous offspring.
Red cell distribution width (RDW) has been
Correspondence and Reprint requests : Dr. Tejinder Singh,
Professor and Head., Department of Pediatrics Christian
Medical College and Hospital, Ludhiana, Punjab, India.141008
Tel/Fax No: 91-0161-2609958
[DOI10.1007/s1209800900144]
[Received August 08, 2007; Accepted May 07, 2008]

Indian Journal of Pediatrics, Volume 76March, 2009

proposed to be a more sensitive indicator to establish the


possible origin of microcytic hypochromic anemia3. The
RDW represents the coefficient of variation of the red
blood cell volume distribution and can be considered an
index of heterogeneity, the equivalent of anisocytosis
observed in the peripheral blood smear.4
In an era of rising cost consciousness, efficient
diagnostic approaches, which can rule in or rule out
diseases with sufficient accuracy so that testing is
minimized, are particularly welcome. Bone marrow
studies are invasive methods and serum ferritin, serum
transferrin, and serum iron are relatively expensive
while RDW, alongside other red cell indices, are a part of
routine blood counts in laboratories using automated
hematology analyzers. If these easily available tests
could be used to screen IDA with acceptably high
sensitivity and specificity, the cost of anemia work-up
would drop considerably because patients with a RDW
suggestive of iron deficiency would not have to undergo
further evaluation.
Various previous studies have debated the role of
RDW in diagnosis of IDA5-1o, with no conclusive word on
the utility of RDW in diagnosing iron deficiency anemia. The
265

Roosy Aulakh et al
present study was designed to test the utility of red cell
distribution width (RDW) in the diagnostic work up of
microcytic hypochromic anemias in Indian children.
MATERIAL AND METHODS
This one year prospective study was carried out in Pediatrics
department of a tertiary care hospital in north India. The
study group included children in age group 6 months to 12
years with microcytic (MCV <75 fl) anemia (hemoglobin <11
g/dl for children between 6 months to 6 years of age and <12
g/dl for those between the ages of 6 and 12 years)11 while
those having received iron therapy anytime over the past one
month, blood transfusion over the past 3 months and
cases with malignancy were excluded. Anemia was
further graded as mild (Hb >10 g/dl), moderate (Hb
between 7-9.9 g/dl) and severe (Hb <7 g/dl).11
They were further classified into iron deficient
anemia and non iron deficient anemia based on the
following standard criteria.12
1) Iron deficient (IDA) children (Group 1): serum
ferritin <7 ng/ml and/or serum TIBC 389 g/dl.
2) Non iron deficient (non-IDA) children (Group 2):
serum ferritin 7 ng/ml and serum TIBC <389 g/dl
Serum ferritin was measured using electrochemiluminescence immunoassay ECLlA and serum TIBC using
Magnesium carbonate precipitation method. The automated
hematology analyzer (ADVIA 60, Bayer diagnostics) was
used to calculate various hematology parameters
including red cell distribution width (RDW). The
instrument is an impedence based three-part
differential system.
RESULTS
The study included 151 children with 106 (70.2%) boys
and 45 (29.8%) girls. The mean age was 3.0 yrs (
2.7yrs) with 39 (25.8%) children up to 1 year, 79 (52.3%)
children between 1 to 5 years, and 33 (21.8%) children 5
or more years of age. Out of these 151 children, 83

(55.0%) had moderate anemia, 34 (22.5%) had mild


anemia and 34 (22.5%) had severe anemia. While group
1 (IDA) included 97 (64.2%) children, with 68 (70.1 %)
boys and 29 (29.9%) girls with a mean age of 3.0 yrs (
2.7 yrs), Group 2 (non-IDA) included 54 (35.8%)
children, with 38 (70.4%) boys and 16 (29.6%) girls with
a mean age of 3.1 yrs ( 2.9 yrs). There was no
statistically significant difference among the three
grades with respect to the age and sex distribution of
the children in IDA and non-IDA groups.
Comparison of RDW between the IDA and nonIDA groups and its variations with severity of anemia:
The mean RDW value was significantly higher in IDA
group (18.37 2.22%) as compared to the non-IDA
group (16.55 1.51%) on unpaired t test (p<0.0001). In
IDA group, the mean RDW value among children with
mild, moderate and severe anemia was 16.60 1.78%,
17.95 1.91% and 20.55 1.32% respectively. The
corresponding values in non-IDA group were 16.03
1.25%, 16.76 1.20% and 16.77 2.68% respectively.
The results of ANOVA test showed a statistically
significant increase in mean RDW values with
increasing severity of anemia among children with
iron-deficient (IDA) microcytic anemia group
(p<0.0001) unlike non iron deficient (NIO) anemia
group (p<0.269).
Sensitivity and specificity of RDW for diagnosing
IDA in microcytic hypochromic anemia: Receiver
operator curves (ROC) were constructed using RDW
values of the children among two groups, which gave a
RDW cut-off value of 17.4% as the value with a best
combination of sensitivity and specificity for microcytic
hypochromic anemia. At this RDW cut-off value of
17.4%, the sensitivity and specificity of RDW in
diagnosing microcytic hypochromic anemia was found
to be 81.0% and 53.4% respectively with a positive and
negative predictive value of 63.0% and 72.2%
respectively.
Furthermore, separate Receiver Operator Curves (ROC)
were constructed for children with mild, moderate and
severe anemia among the two groups. The cut-off value of
RDW with best combination of sensitivity and specificity

T ABLE 1. Sensitivity and Specificity of RDW in Different Published Studies in Comparison to the Present Study
Various studies

Gold Standard used

Cut off value of


RDW (%)

Sensitivity of
RDW (%)

Specificity of
RDW (%)

Present study
(2004-2005)
Zeben et al 5 (1990)
Thompson et al 6 (1998)
Flynn et al 7 (1998)
Gupta et al 8 (1994)
Vishwanath et al9
(2001)
Kim et al 10 (1996)

TIBC, Serum ferritin

17.4

81

53

14.5
15
13.4
17.1
Children - 14.5
Infants 16
15

94
71
94
61.3

59
54
51
92.5

92.1
83.3

90.9
57.7

266

Bone marrow iron


Bone Marrow iron/ Serum Ferritin
Serum Iron, TIBC, Serum Ferritin
Serum Iron, TIBC
Transferrin saturation
Serum ferritin, Transferrin

Indian Journal of Pediatrics, Volume 76March, 2009

Red Cell Distribution Width in the Diagnosis of Iron Deficiency with Microcytic Hypochromic Anemia
for mild, moderate and severe anemia, as obtained from
these ROC curves, was 16.35%, 17.45% and 19.70%
respectively. The sensitivity and specificity was
calculated as 70.6% and 64.7% in mild anemia, 76.3%
and 46.7% in moderate anemia and, 91.3% and 54.6%
respectively in severe anemia.
DISCUSSION
We found a significant increase in mean RDW among
children with iron deficiency anemia (18.372.22%)
compared to non iron deficiency anemia group
(16.551.51%). As obtained from ROC operator curve, at
a RDW cut-off value of 17.4%, the sensitivity and
specificity of RDW in diagnosing microcytic
hypochromic anemia was found to be 81.0% and 53.4%
respectively. On comparison with previous published
studies (Table 1), the present results favor the findings of
Zeben et al 5, Thompson et al6 and Flynn et a1 7, all of
which showed a limited specificity of RDW. While
Thompson et al6 and Flynn et al7 used serum ferritin as
the inclusion criteria, Zeben et al5 used bone marrow
iron as the gold standard. Hence, as they suggested, an
increase in the heterogeneity of RBC size (as measured
by RDW) is seen in all categories of microcytosis.
Although the increase in this parameter is quite
sensitive for iron deficiency, the frequent occurrence of
increased RDW in thalassemia and other conditions
limits its usefulness in the initial diagnostic classification of microcytic anemias.
Similar to Gupta et a18, we also observed an inverse
relationship of RDW with the hemoglobin value
(p<0.0001, ANOVA) in iron deficiency anemia, while no
such correlation was observed in non-iron deficiency
(p=0.269, ANOVA) anemia.
Moreover the findings and recommendations of
western studies on RDW in iron deficiency anemia and
beta-thalassemia trait may not be entirely applicable in
a country like ours with a much higher percentage of
IDA. In such a situation children with BTT, who have
associated IDA, are likely to have a consequent high
RDW and stand to be labeled as iron deficient initially.
Careful follow up after adequate iron therapy following
which the RDW may come back to normal but the low
indices persist, may be required to then further
investigate them for the appropriate heterozygous
hemoglobinopathy.
The only previous published study on Indian
children by Vishwanath et a19, which evaluated 100
anemic children, showed a sensitivity of 92.1% and
specificity of 90.9% for RDW in detecting iron deficiency. However they used transferrin saturation of less
than 16% as gold standard for the diagnosis of iron
deficiency. Moreover a very small group size of 11
children with non-IDA may have affected the results.
Indian Journal of Pediatrics, Volume 76March, 2009

The limitation of the present study is that a higher


prevalence of conditions like subclinical infections and
latent inflammatory disorders in our population, unlike
the Western population, can falsely raise serum ferritin
levels, thereby suggesting that probably we need to
redefine the acceptable normal range of serum ferritin
levels among our population. This would assist in
finding a higher cut-off value needed for serum ferritin
to be used for diagnosis of iron deficiency anemia in a
developing country like ours.
CONCLUSION
A limited specificity of RDW in diagnosis of IDA among
children with microcytic hypochromic children
suggests that further studies like serum ferritin, serum
iron, serum TIBC, bone marrow biopsy and hemoglobin
studies used in a systemic manner are still necessary to
make an accurate diagnosis of the cause of
microcytosis.
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