CARDIAC AND PULMONARY FUNCTIONS
ABNORMALITIES IN CHILDREN WITH BETA
THALASSEMIA MAJOR
Khaled M. (MD)*, Moaz EBN Gabal S. (MD)*, and Hesham Rashid . (MD) **
From departments of Pediatric* and Cardiology**
Benha Faculty of Medicine – Zagazig University - Egypt
ABSTRACT
Background: Chronic administration of large quantities of blood and inappropriate
increase in iron absorption from the gastrointestinal tract inevitably lead to severe
hemosiderosis in the whole body organs with impaired functions. Cardiac disorders
related to biventricular failure are the most frequent cause of death in patients with betathalassemia major. Pulmonary complications in the form of restrictive and obstructive
lung disease due to pulmonary hemosiderosis, recurrent heart failure.
Objective: to assess cardiac and pulmonary functions in patients with beta thalassemia
major.
Patients & methods: This prospective study was conducted on 25 known - thalassemia
major children, 14 males and 11females, their age ranged from 5.4 years to 15 years.
They were selected from the pediatric clinic of Benha University Hospital. The study also
included 25 apparently healthy children as a control group with matched age and sex
during the period from March 2003 to January 2004.
All patients were subjected to thorough history taking , full clinical examination , ECG ,
echocardiography , and pulmonary function testes.
Results: The mean LVEDD ( left ventricular end diastolic dimension ) among cases was
(4.728 + 0.592) which was significantly higher than among controls (4.0 +0.504)
( p<0.05) .The mean LVESD ( left ventricular end systolic dimension ) among cases was
(3.076 +0.58) which was significantly higher than among controls (2.464 + 0.429)
(P < 0.01) .The mean LVM(left ventricular mass) among cases (123.68 +13.034) was
significantly higher than among controls (97.44 + 10.52) and this difference was highly
significant (P < 0.001).The tricuspid E/A ratio was reversed in 5 (20%) of patients
indicating right ventricular diastolic dysfunction. The ECG results revealed voltage
criteria consistent with the diagnosis of left ventricular hypertrophy in 11 patients (44%),
two patients (8%) showed right ventricular hypertrophy ,one patient (4%) showed left
atria dilatation, and none of patients showed right atria dilatation. The mean FVC
( forced vital capacity ) among cases was ( 81.68 + 11.025 ) and among controls
( 87.52 + 3.584 ) and this difference was statistically significant (P<0.05). The mean
FEV1/FVC (forced expiratory volume in first second / forced vital capacity ) among
cases (93.68 + 6.447) was significantly higher than the control group (90.36 + 1.868)
(P < 0.05) .
Conclusions: we conclude that patients with B-thalassemia major have abnormal left
and right dimensions as well as relaxation abnormalities which may be a reflection of
early myocardial damage. This early damage is detectable by a widely applicable
echocardiography. Also the present study has shown that restrictive disease and reduced
lung diffusing capacity are the predominant abnormalities of pulmonary function due to
lung fibrosis .
INTRODUCTION
absorption
from
Thalassemia is the most
gastrointestinal
tract
the
inevitably
common type of chronic hemolytic
lead to severe hemosiderosis in the
anemia in Mediterranean countries.
whole body organs with impaired
It consists of several genetically
functions (1).
determined
disorders
due
to
unequal synthesis of globin amino
Cardiac disorders related to
acids chains that cause ineffective
biventricular failure are the most
erythropoiesis,
frequent cause of death in patients
anemia.
The
depends
on
hemolysis
patients
and
survival
repeated
blood
with
beta-thalassemia
major.
Initial cardiac changes have been
transfusions.
documented
Chronic administration of large
echocardiography before clinical;
quantities
and
ECG
iron
manifestations became apparent (2).
inappropriate
of
blood
increase
in
by
or
conventional
radiological
Pulmonary complications in the
pediatric
form of restrictive and obstructive
University Hospital during the
lung disease due to pulmonary
period
hemosiderosis,
heart
January 2004. The study also
vascular
included 25 apparently healthy
congestion, microthrombosis and
children as a control group with
impaired alveolar growth are of
matched age and sex.
failure,
recurrent
pulmonary
clinic
from
of
March
Benha
2003
to
great interest because of their
effect
on
expectancy
the
patient’s
life
quality
of
and
All cases and control children
were subjected to the following:
1- Full medical history: with
life(3),(4),(5),.
special emphasis on history
of
AIM OF THE WORK
The aim of this work is to
assess
cardiac
and
pulmonary
functions in patients with beta
thalassemia
major
echocardiography,
function
using
pulmonary
tests
and
transfusion,
desferoxamine therapy, and
cardiac and chest symptoms.
2- Clinical
examination:
including
examination
general
and
inspection,
local
palpation,
percussion and auscultation,
electrocardiogram.
PATIENTS AND METHODS
This
blood
study
was
conducted on 25 well known thalassemia major children, 14
males and 11 females, their age
ranged from 5.4 to 15 years. They
were selected randomly from the
of heart and chest.
3- Chest x-ray was done to all
patients.
4- ECG: using Fukuda M-E,
500 AX.
5- Echocardiography:
using
ATL5000, echocardiography
examination
included
dimensional,
color
2
flow
irregularly chelated.
RESULTS
mapping, Doppler display
Table (1) shows that the
and M-mode modalities. The
mean LVEDD, among cases was
LVEDD, LVESD, LVM, FS,
4.728  0.592 and among controls
EF, pulmonary acceleration
was 4.0  0.504 , and this
time , and tricuspid E/A ratio
statistically
were measured.
significant ( P > 0.05 ) . The mean
6- Pulmonary function testing;
FVC and FEV1/ FVC were
measured.
difference
was
LVESD among cases was 3.076 
0.58 and among controls 2.464
0.429 and the difference between
Blood transfusion was given
to all patients when hemoglobin
(Hb) reached or decreased below
10 gm/dl. Every patient received
10-15 ml/kg packed red cells. The
frequency of transfusion depended
on Hb level and
was nearly the
same in all patients, (every 3-4
cases and controls was highly
significant (P < 0.01). The mean
LVM among cases was 123.68 
13.034 and among controls was
97.44  10.52 and this difference
was highly significant (P<0.001).
Also the mean FS and EF among
cases was 31.84 + 5.713 and 61.88
weeks).
+ 4.784 respectively and among
9 patients did not receive
desferoxamine and 16 patients
received it irregularly after blood
transfusion
by
subcutaneous
infusion. That is why all our
patients are poorly transfused and
controls was 29.4 + 2.661 and
60.24 + 2.223 and this difference
was statistically non significant
(P >0.05). The mean pulmonary
acceleration time among cases was
112.76  11.727 and among
controls was 121.6  4.301 and the
showed left atria dilatation, and
difference
none of patients showed right atria
was
significant
dilatation.
(P< 0.05).
Table (2) shows that the
tricuspid E/A ratio was reversed in
Table (4) shows the mean
5 (20%) of patients indicating right
FVC among cases was 81.68 
ventricular diastolic dysfunction.
11.025 and among controls 87.52
that
Table (3) the ECG results
 3.584 and this difference was
revealed
statistically significant (P<0.05).
voltage
criteria
consistent with the diagnosis of
The
left ventricular hypertrophy in 11
cases was 93.68  6.447 and
patients (44%), two patients (8%)
among control group was 90.36 
showed
1.868 and this difference was
right
ventricular
hypertrophy, one patient (4%)
mean
FEV1/FVC
among
statistically significant (P < 0.05).
Table (1): Mean LVEDD, LVESD, LVM, FS, EF, and pulmonary
acceleration time among cases and controls.
controls
Cases
X
Range
SD
X
Range
SD
T
LVEDD In cm
4.728
3.7-5.7
 0.592
4
3.3-4.9
0.504
4.482
<0.05 ( significant )
LVESD In cm
3.076
2-4.1
0.58
2.464
1.2-3.1
0.429
4.242
<0.01( highly significant)
LVM In grams
123.68
90-150
13.034
97.44
80-144
10.52
7.83
<0.001(highly significant)
FS%
31.84
21-41
5.713
29.4
24-35
2.661
1.936
>0.05 ( not significant)
EF%
61.88
54-70
4.784
60.24
55-65
2.223
1.554
>0.05 ( not significant)
112.76
80-123
11.727
121.6
113-130
4.301
3..539
<0.05 ( significant)
Pul. Acc. Time
In milliseconds
P
Table (2): Distribution of the studied groups according to
tricuspid E/A ratio.
Cases
Controls
No.
%
No.
%
T
P value
Normal
20
80.0
25
100.0
236
Reversed
5
20.0
0
0.0
1.118
Total
25
100.0
25
100.0
--
< 0.05
significant
> 0.05
not
significant
--
Table (3): ECG results.
Cases (n = 25)
Controls (n= 25)
LV hypertrophy
LA
Dilatation
RV
hypertrophy
RA
Dilatation
11 (44%)
-
1 (4%)
-
2 (8%)
-
-
Table (4): Mean FVC and FEV1/FVC among cases and controls.
X
Cases
(n = 25)
Range
X
Controls
(n = 25)
Range
SD
SD
T
FVC
81.68
55-94
 11.025
87.52
81-92
 3.584
2.521
FEV1/FVC
93.68
78-102
 6.447
90.36
85-94
 1.868
2.473
P value
<0.05
significant
<0.05
significant
Fig (1) show pulsed wave Doppler on tricuspid valve there is RV
diastolic dysfunction ( Case No. 5)
higher in patient than control
DISCUSSION
Thalassemia is the most
group ( p > 0.05 ),and (P< 0.01)
common type of chronic hemolytic
respectively . Cardiac dilatation
anemia in Mediterranean countries
occurs
secondary
and it is believed to be the most
anemia
which
prevalent of all human genetic
association
diseases. It’s inherited as an
dilatation and chronic anemia. Our
autosomal genetic disorder (6).
finding
to
chronic
means
strong
between
are
cardiac
similar
to
Cardiac disorders related to
Khalifa et al ,(9) who showed a
biventricular failure are the most
significant increase of all cardiac
common cause of death in patients
dimensions by echocardiography
with beta-thalassemia major. Heart
(LAD- LVEDD-LVESD) more in
failure
anemic
regularly transfused patients. They
hypoxia, cardiac hemosiderosis,
stated that these cardiac structural
arrhythmias
changes are due to chronic anemia
is
caused
and
by
hyperdynamic
more than siderosis.
circulatory overload (7).
In the present study finding
Beta-thalassemia major also
affects pulmonary functions where
coincides with Walker
restrictive
Kushner, et al
predominant
pattern
is
abnormality
the
in
the
mean
(11)
(10)
and
, they found that
LVM
index
pulmonary function tests. A mild
significantly
obstructive element can coexist
thalassemic
with restrictive lung disease in a
controls (P < 0.05) , while in the
small number of patients (8).
present study there was highly
In this study both LVEDD
and LVESD were significantly
increased
was
patients
in
versus
significant increased LVM among
cases versus controls (P>0.001 ) .
As regard the FS and EF
right
ventricular
there was no significant difference
dysfunction
between patient and control group
thalassemic patients more than
(P > 0.05). These results are
control group.
similar to other reports which also
demonstrated
preserved
left
was
tricuspid
observed
in
The ECG results revealed
voltage criteria consistent with the
ventricular systolic function inspite
diagnosis
of cardiac dilatation (2), (3).
hypertrophy in 11 patients (44%) ,
Khalifa
Desideri
et
et
al.(9)
al.
(12)
and
found
of
left
ventricular
two patients (8%) showed right
ventricular
hypertrophy
,
one
insignificant difference between all
patient (4%) showed left atria
the studied cases and controls as
dilatation, and none of patients
regards the mean values of EF and
showed
FS (P>0.05).
Khalifa et al.
right
atria
(9)
dilatation.
found voltage
In this study the mean
criteria fulfilling left ventricular
pulmonary acceleration time was
hypertrophy in (33%) of patients,
significantly decreased in patient
voltage criteria of right ventricular
than control group (P<0.05). This
hypertrophy in (15%) of patients
finding coincides with a study
and deep Q in V5 or V6 indicating
done by Hahalis et al.
showed
that
the
(13)
, they
pulmonary
septal hypertrophy in (7%) of
patients.
thalassemic
A significant decrease in
patients results from pulmonary
FVC was found in the patient's
hemosiderosis.
group compared to the control
hypertension
in
In this study and study done
by Gharzuddine et al.
(14)
, the
group (P<0.05). This indicates that
the patient's group have restrictive
pattern of pulmonary function
(17) ,
(mild to moderate restriction).
Cunningham et al.
Also FEV1/FVC was significantly
the restrictive lung disease to be
higher in patient group than in the
not
control (P<0.05). This indicates a
hemosiderosis but also due to
mild degree of obstructive pattern
transfusion
major
due
to
pulmonary
dependent
chronic
-
volume overload with decrease of
patients.
lung capacity causing progressive
of pulmonary function in
thalassemia
only
explained
Analysis of these values indicated
a restrictive and obstructive lung
restriction.
Vittorio et al.
(5)
, found that
disease in the studied cases with
hypoxemia
predominance of the restrictive
abnormality in patients with beta-
pattern.
thalassemia major that stimulates
Pulmonary
patients
with
functions
in
beta-thalassemia
major were the subjects of many
previous studies
(15), (16), (17),
is
a
consistent
excessive alveolar growth. This
hypoxia
induced
alveolar
proliferation is both excessive
that
(with no corresponding increase in
reported the presence of restrictive
bronchial and bronchiolar tree) and
lung disease.
aberrant
Fung et al.
(15)
since
some
of
the
, found that
proliferating alveoli are not in
the means for FEV1 and FVC for
direct continuity with the bronchial
thalassemia
tree. This results in distal gas
group
were
significantly smaller than those for
trapping and air way obstruction.
However,
Carnell; et al. (18), found that
difference in FEV1/FVC was not
restrictive disease and reduced
statistically significant (P>0.05).
lung diffusing capacity are the
the
control
group.
predominate
abnormalities
of
pulmonary function in patients
with
thalassemia
major.
They
appropriate for those developing
suggested that these pulmonary
countries
dysfunctions are due mainly to
affected by thalassemia.
lung fibrosis and/or interstitial
with
a
population
Also the present study has
edema related to iron overload.
shown that restrictive disease and
CONCLUSION
reduced lung diffusing capacity are
From our data we conclude
the predominant abnormalities of
that clinically patients with B-
pulmonary function in patient with
thalassemia major have abnormal
thalassaemia major due to lung
left and right dimensions as well as
fibrosis and / or interstitial edema
relaxation
related
abnormalities
which
to
iron
overload,
cardiac
damage,
may be a reflection of early
hypoxemia,
myocardial damage. This early
decreased alveolar growth and
damage is detectable by a widely
pulmonary vascular involvement
applicable
by microthrombosis.
method which
echocardiographic
may be more
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‫الملخص العربى‬
‫مقدمة ‪:‬‬
‫بعتبر مرض السالسيميا من اهم انواع األنيميا التى ينتج عنها تخثر خاليا الدم الحمراء وينتشر هذا‬
‫المرض فى األقطار التى تطل على البحر األبيض المتوسط نتيجة لخلل جينى متوارث ‪.‬‬
‫وتؤدى عملية نقل الدم المتعددة لهؤالء المرضى إلى زيادة نسبة الحديد بالدم مما يؤدى إلى ترسيبه‬
‫فى أعضاء متعددة من جسم اإلنسان ‪ .‬ويؤدى ترسب الحديد بالقلب إلى فشل وظيفى فى البطينين‬
‫األيمن واأليسر كما يترسب فى الرئتين ويؤدى إلى فشل فى الوظائف التنفسية ‪.‬‬
‫الهدف من البحث‪ :‬يهدف البحث إلى االكتشاف المبكر للخلل الوظيفى فى القلب وكذلك الرئتين‬
‫فى مرضى انيميا البحر المتوسط ‪.‬‬
‫طرق البحث ‪ :‬تم اجراء البحث على ‪ 52‬طفالً يتراوح اعمارهم بين ‪ 2.5‬و ‪ 52‬سنة مصابون‬
‫بانيميا البحر المتوسط ومن المترددين على مستشفى بنها الجامعى – كما تم إجراء البحث على ‪52‬‬
‫طفالً طبيعيين ظاهريا ً من نفس السن والنوع كمتطوعين ‪ .‬وتم أخذ التاريخ المرضى لكل طفل‬
‫وعمل كشف طبى كامل ‪ ,‬وعمل رسم قلب ‪ ,‬وموجات فوق صوتية على القلب وعمل اختبار‬
‫للوظائف التنفسية للرئتين ‪.‬‬
‫نتيجة البحث ‪ :‬وتبين من البحث اآلتى ‪:‬‬
‫زيادة فى حجم البطين األيسر أثناء االنقباض واالنبساط فى مرضى أنيميا البحر المتوسط بالمقارنة‬
‫بالمتطوعين ‪ ,‬كما وجد أن ‪ % 52‬من المرضى يعانون من خلل فى الوظيفة االنبساطية للبطين‬
‫األيمن ‪ .‬كما أثبت البحث أن هناك ‪ % 55‬من المرضى المصابين بأنيميا البحرالمتوسط يعانون من‬
‫تضخم فى البطين األيسر ‪ ,‬ونسبة ‪ % 8‬تضخم بالبطين األيمن ‪ .‬كما أثبت البحث وجود خلل فى‬
‫الوظيفة التنفسية للرئتين فى مرضى أنيميا البحرالمتوسط بالمقارنة بالمتطوعين‪.‬‬
‫الخالصة ‪ :‬إن مرضى أنيميا البحرالمتوسط يعانون من خلل فى الوظيفةاالنبساطية للبطين األيمن‬
‫وزيادة فى حجم البطين األيمن واأليسر ويمكن بمتابعة هؤالء المرضى االكتشاف المبكر لهذا الخلل‬
‫من خالل عمل متابعة بالموجات فوق الصوتية على القلب ‪.‬‬
‫كما أن هؤالء المرضى أيضا ً يعانون من خلل فى الوظائف التنفسية للرئتين نتيجة لترسيب الحديد‬
‫بهما مما يؤدى إلى حدوث تليف فى نسيج الرئتين ‪.‬‬