Importance of RDW Value in Differential Diagnosis

of Hypochrome Anemias
D. Aslan, F. Gu mru k, A. Gu rgey, and C . Altay*
Department of Pediatric Hematology,
_
Ihsan Dog ramac 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 2040 years of age (n = 29), b thalassemia traits (b-TT) with an age range
of 1860 years (n = 49), iron deciency anemia (IDA) in individuals aged 118 years (n =
27), and in controls with an age range of 2040 years (n = 20). Although red blood cell
count, MCV, and MCH values showed no statistically signicant differences between db-
TT and b-TT, the mean RDW value was signicantly 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 signicant rise in RDW in IDA 57 days
after initiation of iron therapy (P = 0.00) which was continued to rise up to the 4
th
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. 69:3133, 2002. 2002 Wiley-Liss, Inc.
Key words: thalassemia; iron deciency; RDW; microcytosis; hypochromia
INTRODUCTION
Red cell distribution width (RDW) was introduced
as an important parameter in the dierential diag-
nosis of iron deciency and b thalassemia trait (b-TT)
[1,2]. Increased RDW value indicates anisocytosis,
and hence, in addition to iron deciency 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
A
2
, 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 dierent 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 dierentiation
of d-b thalassemia from b thalassemia, a thalassemia,
and iron deciency anemia in classical textbooks.
Therefore, d-b thalassemia traits, b thalassemia traits,
and patients with iron deciency were re-evaluated in
order to dene the importance of RDW values in
distinguishing these entities.
MATERIALS AND METHODS
A total of 29 cases of obligatory db-TTs 2040
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
1860 years who had common b thalassemia muta-
tions that are common in the Turkish population:
IVSI-110 GA, IVSII-1 GA, or )30 TA; 27
children with IDA with an age range of 118 years
were also included in the study. Twenty subjects with
an age range of 2040 years served as controls. Age
dierence in the dierent groups was ignored as it was
not found to be critical in comparing RDW values.
Contract grant sponsor: TUBA, Turkish Academy of Sciences (to
C .A.).
*Correspondence to: C ig dem Altay, M.D., Professor of Pediat-
rics, Department of Pediatric Hematology,
_
Ihsan Dog ramac
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
American Journal of Hematology 69:3133 (2002)
2002 Wiley-Liss, Inc.
DOI 10.1002/ajh.10011
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 deciency
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 57 days, 2 weeks, 4 weeks, 6 weeks, and 8 weeks
after institution of oral iron therapy (36 mg/kg
per day).
Hematological studies were performed according to
standard procedures. Molecular pathology of b and d
thalassemia was identied by previously published
procedures [8].
Statistical analysis used the MannWhitney U-test.
RESULTS
The RDW values in patients with d-b thalassemia
and some of the other hematological parameters of
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.
DISCUSSION
Because of many similarities in red cell indices,
RDW emerged as an important parameter to dier-
entiate thalassemia trait and iron deciency anemia.
The variation between the sizes of red cells is reected
by the degree of anisocytosis and as widening in the
RDW value. Institution of iron therapy in iron de-
ciency anemia results in an additional rise in RDW
value in 57 days after initiation of iron therapy
which coincides with reticulocytosis and continuously
rises up to 4th week then starts to decline (Fig. 2). In b
and a thalassemia traits, almost all red cells are
microcytic because decient synthesis of the globin
chain resulting from thalassemia mutations expresses
itself in all of the red cell precursors. Consequently,
RDW values are relatively constant. Our observation
of increased RDW in d-b thalassemia conrms two
previous studies [4,5] that also showed increased
RDW in db-TT. Heterogeneous distribution of Hb F
among red cells in d-b thalassemia traits suggests that
although recessive pathology should express itself
equally in all erythroid precursor cells, an actual in-
crease in Hb F synthesis took place in F cells only.
Therefore, in db-TT, the presence of a mixed red cell
population, consisting of microcytic cells with un-
compensated reduction in b-globin synthesis, is re-
ected as an increase in RDW.
In iron deciency, a signicant rise in RDW value
starting from the 5th day of therapy is an important
early nding for conrmation of iron deciency and
TABLE I. Means (+1 SD) of Some of the Hematological Parameters of d-b Thalassemia Traits, b Thalassemia Traits, Iron Deciency
Anemia Patients, and Controls*
db-TT
1
b-TT
2
IDA
3
Normal
n = 29 n = 49 n = 27 n = 20
RDW(%) 20.14 1.21
a,b
14.88 1.77
a,c
18.00 1.94
c,d
12.49 0.63
b,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( 10
12
/L) 5.51 0.66 5.76 0.82 4.64 0.46 4.59 0.46
*Superscript letters indicate statistically signicant values.
a
db-TT vs. b-TT,
b
db-TT vs. Normal, P < 0.001;
c
b-TT vs. IDA, P < 0.01;
d
IDA; vs.
Normal, P< 0.001.
1
d-b Thalassemia traits.
2
b Thalassemia traits.
3
Iron deficiency anemia.
Fig. 1. RDW values of d-b thalassemia traits, b thalassemia
traits, iron deciency anemia patients, and normal controls.
In each box plot, the lower and upper bars represent the
10
th
and 90
th
percentiles, respectively; the lower and upper
ends of the box represent the 25
th
and 75
th
percentiles,
respectively; and the line inside the box represents the
median RDW values.
32 Aslan et al.
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
easily missed. This information is useful in the dif-
ferential diagnosis of iron deciency and thalassemia
syndromes.
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Fig. 2. Changes in RDW values in IDA after iron treatment.
In each box plot, the lower and upper bars represent the
10
th
and 90
th
percentiles, respectively; the lower and upper
ends of the box represent the 25
th
and 75
th
percentiles,
respectively; and the line inside the box represents the
median RDW values.
Hypochrome Anemias and RDW 33