Screening for Beta Thalassemia Trait

Journal of Rawalpindi Medical College (JRMC); 2014;18(1):158-160
Original Article
Screening for Beta Thalassemia Trait
Raiz Ahmed Qazi*, Rabia Shams *, Hamid Hassan**, Naghmi Asif ***
* Department of Pathology , Peoples University of Medical and Health Sciences, Nawabshah;** Gulab Devi Hospital Lahore;
*** Department of Pathology, Islamabad Medical and Dental College
Abstract
thalassemia major and beta thalassaemia minor.
Clinical features of beta thalassaemia major includes
severe type of haemolytic anaemia appearing at 06
month of age when fetal haemoglobin changes into the
adult haemoglobin, hepatosplenomegaly and mongol
like face due to the bone changes. Estimation of
haemoglobin red blood cell indices, peripheral blood
smear reveals microcytic hypochromic anaemia
usually with nucleated red blood cells and
haemoglobin
electrophoresis
reveals
decrease
haemoglobin A with variable increase in haemoglobin
F. The patients with beta thalassemia minor are
asymptomatic and may be diagnosed because of
presence of microcytic hypochromic red blood cells
with mild anaemia. Haemoglobin electrophoresis in
these patients reveals an increased haemoglobin A2
level.4 To differentiate the types of microcytic
hypochromic anemia such as iron deficiency anemia
and beta thalassemia trait, the hemoglobin
concentration, RBC count and mean corpuscular
volume estimation are useful laboratory tests.5 For
any CBC showing low hemoglobin, MCV <75,MCH
<25 and RBC count > 5.0 millions/cmm. Hb
Electrophoresis at alkaline pH should be done after
excluding iron deficiency. An elevated HbA2 is
diagnostic of β-thalassaemia trait. For normal HbA2
level with low MCV & MCH, consider alternative
diagnosis viz. iron deficiency anaemia and αthalassaemia trait. .6-9 In Pakistan, overall life
expectancy of thalassaemic children is around 10 to 12
years. For proper management of a thalassaemic child
which include enough and safe blood supply and best
iron chelation therapy along with other medical and
psychosocial management the total expenditure on the
management of thalassaemic children throughout the
country is enormously high and most of the children in
Pakistan suffering from thalassaemia are getting sub
optimal treatment.
Thus the prevention of beta
thalassemia major is more important aspect of disease
management. Screening to identify carriers, genetic
counselling, and prenatal diagnosis (done by analysis
of DNA of chorionic villous sampling in 10-12 weeks
of pregnancy) can greatly reduce the rate of birth of
affected infants and improve the prognosis of affected
Background : To evaluate the prevalence of beta
thalassemia trait (BTT) among the students of
schools, colleges and universities of Nawabshah city.
Methods: In this descriptive cross sectional study
students of schools, colleges and universities of
Nawabshah were selected. The blood samples from
these subjects were tested for complete blood count,
and red cell indices. The microscopic examination of
peripheral blood smears stained with Field’s stain
was performed for the morphology of red blood
cells. Serum ferritin and automated haemoglobin
electrophoresis at cellulose acetate alkaline pH was
performed. Subjects with microcytic hypochromic
blood picture and low ferritin level were not
subjected to haemoglobin electrophoresis.
Results: In total of 521 subjects 65.4% were females,
with female to male ratio of 1.8:1. Mean age was 17.5
years. On screening diagnosis of beta thalassemia
trait was made in 4.9% cases and haemoglobin
electrophoresis showed mean haemoglobin A2 of
5.8% in these cases. The microscopic examinations of
peripheral blood smears among the subjects with
BTT showed microcytic hypochromic red blood cells
with presence of target cells.
Conclusion: The prevalence of beta thalassemia
BTT was 4.9%.
Key Words: Beta thalassaemia, Screening
Introduction
Thalassaemia was first discovered in a child with
severe anaemia, splenomegaly and characteristic bone
changes. The name was originated from the Greek
word thalassa (sea) and mias (blood), as its prevalence
was more commonly observed in people of
Mediterranean countries.1 Thalassaemias which are
inherited autosomal recessive disorder are divided
into alpha and beta thalassaemias, the former results
from deletion of alpha gene located on chromosome 16
while Beta thalassaemias is caused by genetic defect
like mutation on the chromosome 11, leading to either
complete absence or decreased synthesis of beta
chain.2 The beta thalassemia is divided into the beta
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Journal of Rawalpindi Medical College (JRMC); 2014;18(1):158-160
Table 1: Demographic and laboratory
parameters of screened subjects
patients. Different approaches have been observed
throughout the world for screening of thalassaemia.
Screening families of index child with thalassaemia
has shown promising results. Screening can be done
for those who are candidates for marriage, or in
schools, colleges or at prenatal clinics. 6-8
Characteristics
Mean age
Sex
Female %
Male %
Subjects and Methods
Total Subjects (n=521)
17.5 years
341 (65.4%)
180 (34.6%)
Female to male ratio 1.8:1
Laboratory parameters
Hemoglobin g/dl
PCV %
MCV fl
MCH pg
MCHC g/dl
RBC count million/cmm
TLC /cmm
Platelet count /cmm
Serum ferritin ug/dl
This cross sectional descriptive study was
conducted at Pathology Department of PUMHS In
total 521 students of schools, colleges & universities of
Nawabshah city were included in the study. The
awareness regarding the thalassemia was created by
distributing pamphlets to the each student and
detailed history including information regarding
history of any family member with beta thalassemia
major was filled. The blood samples from these cases
were taken for the diagnosis of beta thalassaemia trait.
Complete blood counts including haematological
parameters such as haemoglobin g/dl, red cell indices
(PCV, MCV, MCH & MCHC) were performed . The
microscopic examination of peripheral blood smear
stained with Field’s stain was performed for the
morphology of RBC. Serum ferritin concentration was
tested by solid phase Automated Enzyme linked
Immunoassay. Cases with microcytic hypochromic
anaemia and low ferritin levels were excluded. Cases
of microcytic hypochromic picture were evaluated for
beta thalassemia trait on automated haemoglobin
electrophoresis at cellulose acetate alkaline pH.
Hemoglobin A2 was analyzed by micro column
technique .
11.8 g/dl
38.7%
82fl
26.9pg
33.2g/dl
4.5 million/cmm
8000/cmm
310,000/cmm
15 ug/dl
Table 2: Laboratory Parameters in BTT Subjects
Laboratory parameters
RBC mil/cumm (Mean+SD)
MCV fl (Mean+SD)
MCH pg/dl (Mean+SD)
MCHC g/dl (Mean+SD)
RDW % (Mean+SD)
Serum Ferritin ug/dl (Mean+SD)
Hemoglobin A2 level % (Mean+SD)
BTT(n=26)
5.1 + 1.1
72.8 + 5.4
19.9 + 2.5
31.2 + 1.2
13.9 + 2.4
15.4 + 0.7
5.8 + 0.8
Discussion
Beta Thalassemia is a genetically transmitted blood
disorder with a carrier rate of 5-8% and around 5000
children are diagnosed, with beta thalassaemia major,
each year, in Pakistan.9 Carriers of beta thalassaemia
are usually symptomless. Haemoglobin is usually
between 10-12 gm/dl. These people do not require
blood transfusion. Its diagnosis is based on the finding
of raised Hb A2, i.e. between 3.5- 7.0% (normal 1.53.0%) on haemoglobin electrophoresis. Concomitant
iron deficiency and silent mutations can be
confounding in haemoglobin electrophoresis for
thalassaemia trait. In such situations molecular studies
are imperative.9
World over, the carrier rate of BTT varies from 1.7
to 9 %. Approximately, 60,000 children are born with
beta thalassaemia major, annually. In Pakistan carrier
rate varies from 1 to 7 per cent. Each year 5000
children are born with beta thalassaemia major.10-17
Screening for thalassaemia trait can dramatically
Results
Total 521 subjects were screened for BTT including
65.4% females, with female to male ratio of 1.8:1. Mean
age of these subjects was 17.5 years (Table 1). The
mean values of haemoglobin g/dl, RBC count
millions/cmm, PCV %, MCV fl, MCH pg, MCHC
g/dl, TLC count /cmm, and platelet count /cmm
among these subjects were 11.9 g/dl, 4.5
millions/cmm, 82 fl, 38.7%, 26.9 pg, 33.2 g/dl,
8000/cmm and 310,000/cmm respectively. Serum
Ferritin level <15ug/dl was taken as cut off for IDA.
Peripheral blood smear morphology revealed
hypochromic microcytic red cell picture with presence
of target cells in BTT positive case. On Hb
Electrophoresis the mean HbA2 in cases was 5.8% and
HbF was 0.7. Out of total 521 subjects, 26 subjects were
found to be BTT therefore prevalence of BTT was
found out to be 4.9% in this group (Table 2).
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Journal of Rawalpindi Medical College (JRMC); 2014;18(1):158-160
decrease the incidence of thalassaemia major births by
the premarital screening and genetic counselling, as in
Saudi Arabia with 3.4 prevalence rate reported by
Ziad Ahmed M and Mohammad Y.S. 18 In Iran
premarital screening of beta thalassemia was carried
out by estimation of hemoglobin concentration, red
cell indices, microscopic examination of peripheral
blood smear, hemoglobin electrophoresis and genetic
counseling of both partners as reported by Karimi M et
al.19The cases of beta thalassemia major reduced or
even eradicated some countries Cyprus, Greece and
Italy by the process of prenatal diagnosis of
thalassemia during pregnancy with abortion of child
as reported by Leung TN et al.20 Our study of
prevalence of BTT is comparable with local study in
Pakistan and international study in Bangladesh, India,
Srilanka, China and Turkey while detection of BTT by
hematological parameters were confirmed by local
study in Pakistan 17 and international study in
Iran.13,17,19,21
There are several countries in the world where
premarital thalassaemia screening is mandatory as
described in this context but our situation is different
due to the faith, religious facts, illiteracy
and
increased consanguinity. A thalassaemia prevention
bill was moved in Sindh assembly but the
implementation is still pending. Globally, efforts have
been made for prevention of thalassaemias by mass
education and various prevention strategies like, mass
screening, extended family screening of the index
child, prenatal diagnosis and termination of pregnancy
and pre-marital screening. The prenatal diagnosis and
termination of pregnancy is not uniformly practised in
all religions and societies, although increased trend is
seen in modern societies and part of the world with
high literacy rate. For a successful prevention
program, support from all stakeholders including
religious scholars, electronic and print media,
gynaecologists, paediatricians, thalassaemic families,
government and non government organizations is
required.
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Conclusion
1.Thalassaemia is the most common genetic disorder
in our set up.
2.Screening programs are required at the national level
to reduce further burden of beta thalassemia major
births in our community.
20.
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