American Journal of Hematology 69:31±33 (2002)

Importance of RDW Value in Differential Diagnosis

of Hypochrome Anemias
D. Aslan, F. GuÈmruÈk, A. GuÈrgey, and C
Ë . Altay*
_
Department of Pediatric Hematology, Ihsan DogÆramacõ Children's Hospital, Hacettepe University, Ankara, Turkey

Red cell distribution width (RDW) was studied in adults carrying d-b thalassemia traits
(db-TT) who were 20±40 years of age (n = 29), b thalassemia traits (b-TT) with an age range
of 18±60 years (n = 49), iron de®ciency anemia (IDA) in individuals aged 1±18 years (n =
27), and in controls with an age range of 20±40 years (n = 20). Although red blood cell
count, MCV, and MCH values showed no statistically signi®cant differences between db-
TT and b-TT, the mean RDW value was signi®cantly higher in db-TT (20.14 ‹ 1.21) com-
pared to b-TT (14.88 ‹1.77) (P < 0.001). No difference was observed between the means of
RDW in db-TT and IDA (18.00 ‹ 1.94) (P > 0.05). A signi®cant rise in RDW in IDA 5±7 days
after initiation of iron therapy (P = 0.00) which was continued to rise up to the 4th week of
therapy was suggested as an important tool in differentiation of IDA from db-TT. These
observations could be kept in mind in the differential diagnosis of db-TT from b-TT and
IDA by determining the red blood cell count, red cell indices, and RDW only. Am. J.
Hematol. 69:31±33, 2002. ã 2002 Wiley-Liss, Inc.

Key words: thalassemia; iron de®ciency; RDW; microcytosis; hypochromia

INTRODUCTION MATERIALS AND METHODS

Red cell distribution width (RDW) was introduced
as an important parameter in the di€erential diag-
nosis of iron de®ciency and b thalassemia trait (b-TT)
[1,2]. Increased RDW value indicates anisocytosis,
and hence, in addition to iron de®ciency anemia
(IDA), it could be observed in hemolytic anemias
including non-transfused b thalassemia major [3]. The
d-b thalassemia trait (db-TT) is characterized by ele-
vation of Hb F, a normal or decreased level of Hb
A2 , and red cell indices similar to those of b-TT.
Distribution of Hb F among red cells is heteroge-
neous. A rise in RDW in db-TT would be expected
because of the presence of two di€erent red cell
populations. Indeed, two studies have shown that
RDW is increased in d-b thalassemia heterozygotes
[4,5]. However, it seemed that this important obser-
vation did not receive much attention, as these reports
were not referred to in discussions of di€erentiation
of d-b thalassemia from b thalassemia, a thalassemia,
and iron de®ciency anemia in classical textbooks.
Therefore, d-b thalassemia traits, b thalassemia traits,
and patients with iron de®ciency were re-evaluated in
order to de®ne the importance of RDW values in
distinguishing these entities.
ã 2002 Wiley-Liss, Inc.
DOI 10.1002/ajh.10011
A total of 29 cases of obligatory db-TTs 20 40
years of age were the subjects of this study. Thalass-
emia was associated with Sicilian type, gamma G
type, 30-kb deletion, and deletion/inversion types
previously reported from Turkish subjects [6,7]. For-
ty-nine adult cases of b-TT with an age range of
18 60 years who had common b thalassemia muta-
tions that are common in the Turkish population:
IVSI-110 G®A, IVSII-1 G®A, or )30 T®A; 27
children with IDA with an age range of 1 18 years
were also included in the study. Twenty subjects with
an age range of 20 40 years served as controls. Age
di€erence in the di€erent groups was ignored as it was
not found to be critical in comparing RDW values.
Contract grant sponsor: TUBA, Turkish Academy of Sciences (to
CË.A.).
*Correspondence to: CËigÆdem Altay, M.D., Professor of Pediat-
rics, Department of Pediatric Hematology, Ihsan_ DogÆramacõ
Children's Hospital, Hacettepe University, 06100 Ankara, Turkey.
E-mail: caltay@gen.hun.edu.tr
Received for publication 10 March 2001; Accepted 16 July 2001
32 Aslan et al.

Serum iron, serum iron binding capacity, and ferritin

levels were measured in all subjects. The diagnosis of
IDA was made in the presence of at least three of the
following criterion: Hb <11 g/dl, MCV <70 ¯,
transferrin saturation <%10, and serum ferritin level
<10 ng/ml. The subjects with d-b thalassemia trait or
b thalassemia trait who had also iron de®ciency
anemia indicated by transferrin saturation <%10 and
serum ferritin level <10 ng/ml were excluded from the
study. In IDA, RDW was measured at diagnosis and
at 5 7 days, 2 weeks, 4 weeks, 6 weeks, and 8 weeks
after institution of oral iron therapy (3 6 mg/kg
per day).
Hematological studies were performed according to
standard procedures. Molecular pathology of b and d
thalassemia was identi®ed by previously published
procedures [8].
Statistical analysis used the Mann Whitney U-test. Fig. 1. RDW values of d-b thalassemia traits, b thalassemia
traits, iron de®ciency anemia patients, and normal controls.
In each box plot, the lower and upper bars represent the
RESULTS 10th and 90th percentiles, respectively; the lower and upper
ends of the box represent the 25th and 75th percentiles,
The RDW values in patients with d-b thalassemia respectively; and the line inside the box represents the
and some of the other hematological parameters of median RDW values.
various groups are given in Table I and Figure 1. The
changes of RDW values associated with iron therapy
in IDA are shown in Figure 2. chain resulting from thalassemia mutations expresses
itself in all of the red cell precursors. Consequently,
RDW values are relatively constant. Our observation
DISCUSSION of increased RDW in d-b thalassemia con®rms two
previous studies [4,5] that also showed increased
Because of many similarities in red cell indices, RDW in db-TT. Heterogeneous distribution of Hb F
RDW emerged as an important parameter to di€er- among red cells in d-b thalassemia traits suggests that
entiate thalassemia trait and iron de®ciency anemia. although recessive pathology should express itself
The variation between the sizes of red cells is re¯ected equally in all erythroid precursor cells, an actual in-
by the degree of anisocytosis and as widening in the crease in Hb F synthesis took place in F cells only.
RDW value. Institution of iron therapy in iron de®- Therefore, in db-TT, the presence of a mixed red cell
ciency anemia results in an additional rise in RDW population, consisting of microcytic cells with un-
value in 5 7 days after initiation of iron therapy compensated reduction in b-globin synthesis, is re-
which coincides with reticulocytosis and continuously ¯ected as an increase in RDW.
rises up to 4th week then starts to decline (Fig. 2). In b In iron de®ciency, a signi®cant rise in RDW value
and a thalassemia traits, almost all red cells are starting from the 5th day of therapy is an important
microcytic because de®cient synthesis of the globin early ®nding for con®rmation of iron de®ciency and

TABLE I. Means (+1 SD) of Some of the Hematological Parameters of d-b Thalassemia Traits, b Thalassemia Traits, Iron De®ciency
Anemia Patients, and Controls*

db-TT1 b-TT2 IDA3 Normal

n = 29 n = 49 n = 27 n = 20
a,b a,c c,d
RDW(%) 20.14  1.21 14.88  1.77 18.00  1.94 12.49  0.63b,d
Hb(g/dl) 12.38  1.19 12.41  1.60 9.35  0.81 13.79  1.30
MCV(¯) 67.53  4.57 66.07  4.28 63.33  6.66 86.40  2.90
RBC(´ 1012/L) 5.51  0.66 5.76  0.82 4.64  0.46 4.59  0.46

*Superscript letters indicate statistically signi®cant values. adb-TT vs. b-TT, bdb-TT vs. Normal, P < 0.001; cb-TT vs. IDA, P < 0.01; dIDA; vs.
Normal, P< 0.001. 1d-b Thalassemia traits. 2b Thalassemia traits. 3 Iron deficiency anemia.

Fig. 2. Changes in RDW values in IDA after iron treatment.
In each box plot, the lower and upper bars represent the
10th and 90th percentiles, respectively; the lower and upper
ends of the box represent the 25th and 75th percentiles,
respectively; and the line inside the box represents the
median RDW values.
for distinguishing it from other hypochromic ane-
mias. This helps to avoid further laboratory studies
(Fig. 2). The increase in RDW in IDA is a better
parameter than is the rise of the reticulocyte count
because the former continues to rise for several weeks,
whereas the reticulocytosis is of short duration and
Hypochrome Anemias and RDW 33
easily missed. This information is useful in the dif-
ferential diagnosis of iron de®ciency and thalassemia
syndromes.
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