A Clinicohaematological Profile of Splenomegaly

Varsha S. Dabadghao*, Arundhati G.Diwan**, Amol M. Raskar***

*Assistant Professor, **Professor and Head,
***Resident, Department of Medicine, Bharati
Vidyapeeth University Medical College, Pune.
Abstract
Splenomegaly is usually a pointer to serious disease, and its aetiology should be
thoroughly investigated. The aim of the present study was to evaluate the causes and
clinicohaematological profile of splenomegaly. This cross sectional, observational
study was conducted on hundred adult patients with splenomegaly admitted to
medical wards in one year. Grading of splenomegaly was done by Hackett's grading.
Thorough relevant investigations were carried out. Most patients were below 40
years of age. The commonest aetiology in this study was inflammatory, in 49%
patients. The commonest grade of splenomegaly was I and II in 87% patients, while
commonest cause of grade IV splenomegaly was neoplastic. Malaria was the
commonest aetiology among inflammatory causes. In this study, autoimmune
haemolytic anaemia was an important cause of hyperplastic splenomegaly.
Hepatomegaly was associated with splenomegaly in 73% cases. 21% of patients had
severe anaemia and the commonest cause was hyperplastic splenomegaly. The
commonest smear picture was microcytic hypochromic anaemia, while bone marrow
showed dimorphic picture as commonest.
Introduction
n normal individuals, spleen is not
Ipalpable and a palpable spleen may be
1
an indicator of a serious disorder. In a
symptomatic patient, splenomegaly
should always be taken seriously and
thorough investigations should be carried
out to ascertain the aetiology. Causes may
1,2
vary with diseases prevalent in that area.
The degree of splenomegaly varies with
the disease causing it. Most of the chronic
condi ti ons l i ke chroni c mal ari a,
myeloproliferative diseases, haemolytic
anaemi as et c. l ead t o massi ve
splenomegaly while in most acute
conditions, patients present with a mild
1
enlargement of spleen. The aetiology of
splenomegaly thus differs with the grade of
splenomegaly at presentation, the age of
the patient, clinical features, and
associated signs and symptoms. In spite of
advances in haematology, immunology,
radiology and ultrasonography, there
remains a group of patients of enlarged
spleen with a final diagnosis of
"Splenomegaly of Indeterminate origin" or
"obscure splenomegaly", where a definitive
diagnosis cannot be reached even after
every possible investigation, both invasive
2
and non-invasive.
The present study is an attempt to
elucidate the causes of splenomegaly and
also to study its clinicohaematological
profile. The aim of this study was to
evaluate the aetiology of splenomegaly
clinically and with help of investigations
which were possible in this hospital, and to
correlate the haematological parameters
and grading of splenomegaly.
Bombay Hospital Journal, Vol. 54, No. 1, 2012 10
Material and Methods
This cross-sectional, observational
study was conducted on patients admitted
in a teaching hospital in Western
Maharashatra over a period of one year.
Institutional ethical committee's clearance
was taken. Hundred patients more than
18 yrs of age admitted in medical wards,
diagnosed with a palpable spleen on per
abdominal examination, were selected.
The spect rum and aet i ol ogy of
splenomegaly is different in children,
hence paediatric age group was excluded
from the study.
Confirmation was done by ultrasound
and patients with spleen size more than 13
cm on ultrasound were included. The
cases included were of splenomegaly
a l o n e , h e p a t o s p l e n o me g a l y ,
h e p a t o s p l e n o m e g a l y w i t h
lymphadenopathy and splenomegaly with
pallor, icterus and petechiae.
Grading of splenomegaly was done by
Hackett's grading. This method has been
accepted by WHO for usage in malaria
surveys and can be used for routine
3
clinical examination also.
Class 0 - Spleen not palpable even on
deep inspiration.
Class 1 - Spleen just palpable below
costal margin on deep inspiration.
Class 2 - Spleen palpable but not
beyond a horizontal line half way
between the costal margin and
umbilicus.
Class 3 - Spleen palpable more than
half way to umbilicus, but not below a
line running horizontally through
umbilicus.
Class 4 - Spleen palpable below
umbilicus but not below a horizontal
line between umbilicus and pubic
symphisis.
Class 5 - extending lower than class
4
Hackett's classes 1 and 2 were
considered as Mild splenomegaly, class 3
as Moderate splenomegaly, and class 4
and 5 were considered as Massive
splenomegaly.
Fo l l o wi ng de t ai l e d phy s i c al
examination, patients underwent various
investigations such as : Haemogram with
peripheral blood smear, reticulocyte
count, complete blood count, liver and
renal function tests and bacterial culture
of blood and stool. Serological tests such
as HIV, viral markers of hepatitis, Widal
test, dengue antibodies test, Rapid Malaria
test, leptospira antibodies test were done.
Tests for haemolysis such as sickling test,
osmotic fragility test, LDH and G6PD were
done as indicated. Lymph node biopsy,
liver biopsy, bone marrow aspiration and
biopsy (wherever indicated) were done.
Radiological investigations such as
ultrasonography of abdomen, 2D
Echocardiography of heart, barium
studies, CT scan, MRI Study (wherever
indicated) were done. Gastrointestinal
endoscopy was performed when required.
Investigations were done as required by
clinical judgement, to diagnose the cause
of splenomegaly. Patients where the cause
r e ma i ne d o bs c ur e a f t e r t he s e
investigations, were designated as a group
of "Splenomegaly of Indeterminate Origin".
Results
In this study, there were 55 males and
45 female patients,the male to female ratio
was 1.2:1. Of these 100 patients, 24%
patients were in the age group of 21-30
Bombay Hospital Journal, Vol. 54, No. 1, 2012 11
years and another 22% in the age group of
31-40 years .Only 6% patients were in the
above 60 year age group
Table 1: Age and Sex distribution
Fever was the commonest clinical
symptom seen in 48 patients followed by
generalised weakness (n=15), pain in
abdomen (n=14), abdominal distension
(n=13), dyspnoea (n=11), petechiae and
ecchymosis (n=7), jaundice (n=6), swelling
over legs (n=3), gastrointestinal bleeding
(n=3), joint pains (n=2). There was
dysphagia, diarrhoea, altered sensorium
and haematuria in 1 patient each.
Aetiology could be credibly established
by investigations in 98 out of 100 patients,
49% of cases were due to inflammatory
causes, 23% due to congestive, 13% due to
neoplastic and 13% due to hyperplastic
aetiology. In 2% cases, cause was
indeterminate.
Table 2: Aetiology
In inflammatory causes, which numbered
49 cases out of 100, malaria was the
commonest cause with 15 patients
(30.61%). Other causes were : dengue (7
pati ents, 14. 28%) , enteri c f ever ( 7
patients,14.28%), HIV (4 patients,
8.16%),tuberculosis (4 patients, 8.16%),
leptospirosis (3 patients, 6.12%), hepatitis
B (3 patients, 6.12%), hepatitis C (2
patients, 4.08%), pyogenic liver abscess (2
patients, 4.08%), brucellosis (1 patient,
2.04%) and infective endocarditis (1
patient, 2.04%). In congestive causes,
which numbered 23 patients out of 100,
l i ver ci rrhosi s ( si nusoi dal portal
hypertension) was the commonest cause
in 19 patients (82.6% cases), cardiac
c a us e s ( po s t s i nus o i da l po r t a l
hypertension) were present in 3 patients
(13.04% cases) and portal vein thrombosis
(pre sinusoidal portal hypertension) in 1
patient(4.34% cases). Out of the 19 cases
of liver cirrhosis, 9 cases were alcoholic
liver disease with cirrhosis and portal
hypertension, 2 cases were autoimmune
liver diseases and 1 case was of Wilson's
disease. In 7 cases, exact cause of
cirrhosis could not be determined . Among
neoplastic causes (13 patients), there were
3 cases each of chronic myeloid leukaemia
(CML) and hepatocellular carcinoma
(23.07%). There were 2 cases each of acute
myeloid leukaemia (AML) and hairy cell
leukaemia(15.38%). There was 1 case each
of acute lymphoblastic leukaemia (ALL),
lymphoma and myelofibrosis(7.69%).
Hyperplastic splenomegaly (13 patients)
included the haematological causes. In
this study, there were 5 cases of
autoimmune haemolytic anaemia (38.46%
), 3 patients each of iron deficiency
anaemi a and di morphi c anaemi a
(23.07%). There was one case each of
thalassaemia major and polycythaemia
vera ( 7.69%) .
12 Bombay Hospital Journal, Vol. 54, No. 1, 2012
Aetiology of patients
Inflammatory
Congestive
Hyperplastic
Neoplastic
Obscure
Distribution of patients with respect to age
(years) and gender
Male
Female
8
5
10
14
15
11 11
7
9
2
4 4
11-20 21-30 31-40 41-50 51-60 > 60
Age (years), taken from 18 yrs
16
14
12
10
8
6
4
2
0
N
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m
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r

o
f

p
a
t
i
e
n
t
s
23% of spl enomegal y due to
inflammatory aetiology was grade I (by
Hacketts grading), while 21% was grade II.
Only 1% of inflammatory spleens were
grade IV. 15% of splenomegaly due to
congestive aetiology was grade II. 2% of
splenomegaly due to neoplastic aetiology
were grade III and IV each while most were
grade II. Most spleens in hyperplastic
splenomegaly (9%) were grade I.
Table 3:Correlation between grades of
splenomegaly and aetiology
Hence grade I and II were the common
findings in nearly 87% patients in this
study. Among grade IV spleens, the
commonest cause was neoplastic.
Hepatomegaly was associated with
splenomegaly in 73% cases. 42 out of 49
patients with inflammatory splenomegaly
had hepatomegaly (85.71%). Out of these,
maximum number of patients had liver
size 2-4 cm (17 patients, 40.47%). Only 10
patients had liver size > 6 cm (23.81%). 12
out of 13 patients with neoplastic
splenomegaly also had concomitant
hepatomegaly (92.31%). Out of these, 5
patients had liver size > 6 cm (41.66%) and
3 patients had size 2-4 cm (25%).
22 out of 55 (40%) male patients had
moderate to severe anaemia, 27 out of 45
(60%) female patients had moderate to
severe anaemia. 21% of patients had
severe anaemia with haemoglobin levels
less than 7 gm%.
8 patients out of 21 who had severe
anaemia (Hb < 7 g%) with splenomegaly
had hyper pl ast i c spl enomegal y
(haematological causes). 29% of patients
had moderate anaemia with haemoglobin
levels between 7-10 gm%. 16 patients with
severe anaemia had grade I & grade II
splenomegaly.15 patients with grade II
spleen had moderate anaemia.
Table 4:Correlation between grades of spleen
and haemoglobin
In peripheral blood smear(PBS), 28%
patients had microcytic hypochromic
anaemia and 25% had normocytic,
normochromic picture. Dimorphic picture
was seen in 5% patients. Malarial parasite
was seen in PBS of 15% patients and there
was t hr ombocyt openi a i n 10%.
Myeloblasts were also seen in 6% patients
Table 5:Findings on peripheral blood smear
Bombay Hospital Journal, Vol. 54, No. 1, 2012 13
Aetiology vs Grade of splenomegaly of patient
N
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Grade I
Grade II
Grade III
Grade IV < 7 gm%
7-10 gm%
10-12 gm%
> 12 gm%
16
14
12
10
8
6
4
2
0
N
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Grade of splenomegaly vs haemoglobin (gm%) level of patient
Grade I
Grade of splenomegaly
Grade II Grade III Grade IV
Peripheral blood smear findings
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20
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Number of
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17 patients underwent bone marrow
examination for further investigation of
splenomegaly. The most common finding
was dimorphic anaemia in 3 patients
(17.64%). 2 patients had iron deficiency
anaemia, anaemia of chronic disease,
acute myeloid leukaemia and chronic
myeloid leukaemia (11.76%). Reactive
lymphocytosis, acute lymphoblastic
leukaemia, myelofibrosis and Hodgkin's
lymphoma were seen in 1 patient each
(5.88%). In 2 patients, the marrow was
reported as normal
Table 6:Bone Marrow findings
6 patients underwent liver biopsy as
part of the investigation of splenomegaly.
Out of that, 3 were found to have
hepatocellular carcinoma. In 2 patients,
biopsy was non conclusive and 1 showed
lymphocytic infiltration .
On ultrasound, 87 patients had mild
splenomegaly, 9 patients had moderate
and 4 patients had massive splenomegaly.
6 6 p a t i e nt s ha d c o nc o mi t a nt
hepatomegaly, 14 patients had liver
cirrhosis with portal hypertension and 12
patients had ascites. 4 patients had
uncomplicated liver cirrhosis and 3 had
portal vein thrombosis. Abdominal
lymphadenopathy was seen in 2 patients
while liver abscess was diagnosed in 2. The
remaining 3 patients had echogenic
lesions in liver which later were confirmed
on histopathological examination to be
hepatocellular carcinoma.
Discussion
Splenomegaly in a symptomatic
patient is of considerable clinical
significance. One needs to investigate the
patient thoroughly as many of the
conditions causing splenomegaly are
1,2
treatable. In the present study, hundred
patients of splenomegaly were studied.
In this study, maximum cases were in
age group of 21 - 40 years (46%). The male:
female ratio was 1.2:1. In a study by
Nadeem et al, the male to female ratio was
1
4:1.
In the present study, fever was the
commonest clinical symptom seen in 48
patients followed by generalised weakness
(n=15). The clinical presentation seen in
this study is comparable to a study by
2
Sunderasan et al on splenomegaly.
A classification given in Wintrobe's
text book of clinical haematology was
adopted which divides aetiology in the
4
various groups. In this study, the causes
of splenomegaly were inflammatory (49%),
congestive (23%), neoplastic (13%),
hyperplastic (13%), and obscure aetiology
(2%). Among the inflammatory aetiology,
malaria was the commonest with 15
patients(30.66%). In a study by Nadeem et
al, malaria was the commonest cause of
1
splenomegaly (25% patients). In that
study, a disease wise aetiology was
elucidated while in the present study,
aetiology has been grouped as described
above. In a study conducted on hundred
patients of splenomegaly by Sundaresan
et al, malaria was the commonest cause of
14 Bombay Hospital Journal, Vol. 54, No. 1, 2012
Bone marrow findings
Dimorphic anaemia
Iron deficiency anaemia
Anaemia of chronic
disease
Reactive lymphocytosis
Acute myeloid leukaemia
Acute lymphoblastic
leukaemia
Chronic myeloid leukaemia
Hodgkins lymphoma
Within normal limits
Myelofibrosis
2
splenomegaly, observed in 22 patients. In
the present study, there was associated
hepatomegaly in 100% of patients of
malaria.
Hyperreactive malarial splenomegaly
is diagnosed on the basis of massive
splenomegaly, high circulating titres of
malarial antibodies, elevated IgM levels,
lymphocytic infiltration of hepatic
sinusoids, haematologic findings of
hypersplenism, exclusion of other causes
of splenomegaly and clinical and
2
immunological response to antimalarials.
In the present study, a diagnosis of
hyperreactive malarial splenomegaly has
not been offered as there was no definite
history of malaria in the past and
immunological investigations for malaria
were not done.
Inflammatory causes depend on the
prevalence of those infections in a given
tropical area. In present study, the other
inflammatory causes were enteric fever,
dengue, tuberculosis, HIV, leptospirosis,
hepatitis B and C, in order of number of
cases found which are comparable to other
1,2
studies. In few studies on dengue,
splenomegaly was found in a wide range
5,6
between 8.2% and 60.0%. In a study on
f e v e r o f unkno wn o r i g i n a nd
splenomegaly, a diagnosis of tuberculosis
was established in 10% of patients who
7
underwent diagnostic splenectomy. In
one study of eighty five cases of AIDS,
splenomegaly was found in 59 cases (69.4
8
%). In patients with AIDS, additional
pathogens like P. Carinii, Toxoplasma
gondii, Aspergillus and fungi are the
9
recognised causes of splenic abscesses.
In present study, hepatitis related
splenomegaly due to various infections
has been grouped under inflammatory
causes. Hepatitis B and C viruses are two
of the main causative agents of chronic
10
liver disease (CLD) all over the world.
High prevalence rates of co-infection with
hepatitis C virus have been detected
among patients with severe chronic
hepatitis, cirrhosis and inactive HBV
11
infection. Few Indian studies have shown
wide variation in HCV prevalence in
12
patients of chronic liver diseases. In a
study by Nadeem et al from Pakistan, 9%
splenomegalies were due to hepatitis
related disease, either chronic hepatitis or
1
cirrhosis.
Next common aetiology in the present
study was congestive, with 23% patients.
Of these 23 cases, maximum cases were of
liver cirrhosis (82.60%). Cardiac causes
and portal vein thrombosis were also
found. Data from studies indicate that
cirrhosis with portal hypertension is a
common cause of moderate (4-8 cm)
13
splenomegaly.
According to Nadeem et al, 9.4% cases
had splenomegaly due to cirrhosis (mostly
1
post hepatitic). In a study on
autoimmune hepatitis, splenomegaly was
f o und i n 34. 2% pat i e nt s and
14
hepatomegaly in 44.7%. In an analysis of
patients with portal vein thrombosis
without cancer or cirrhosis, 75% had
15
splenomegaly.
In present study, among neoplastic
causes (13 patients), there were 3 cases
each of chronic myeloid leukaemia and
hepatocellular carcinoma (23.07%). Also
seen were acute myeloid leukaemia, hairy
cell leukaemia, acute lymphoblastic
leukaemia, lymphoma and myelofibrosis.
In the study by Nadeem et al, neoplastic
Bombay Hospital Journal, Vol. 54, No. 1, 2012 15
splenomegaly accounted for 16.2% of
cases out of which, acute myeloid
1
leukaemia was maximum.
All patients of CML in present study
had hepatomegaly (100%) while in a study
on CML, the incidence of associated
16
hepatomegaly was 68%.
In this study, there were 13 cases of
hyperplastic splenomegaly: maximum
were cases of autoimmune haemolytic
anaemia (38.46%). Also seen were iron
deficiency anaemia, dimorphic anaemia
(23.07%) and one case of thalassaemia
and pol ycythaemi a vera ( 7.69%) .
Hyperplastic splenomegaly accounted for
the second commonest aetiological group
of splenomegaly in a study by Nadeem et al
( approxi mat el y 30% cases) wi t h
1
nutritional anaemia as commonest cause.
Haemolytic anaemia accounted for 4.2%
1
cases. 80% of the cases of autoimmune
haemolytic anaemia in the present study
also had hepatomegaly. In a study on 40
cases of primary autoimmune haemolytic
anaemia, splenomegaly was found in 45%
17
cases and hepatomegaly in 47.5% cases.
In a study on 21 patients of autoimmune
haemolytic anaemia (AIHA), hepatomegaly
and splenomegaly was seen in 76% and
18
81% respectively.
This study graded splenomegaly
according to the Hackett's grading, which
3
is a WHO accepted grading. Grade II
splenomegaly was the commonest finding
in this study which constituted 44% of
total cases. Maximum cases of grade II
splenomegaly were from inflammatory
group (47.72%) followed by congestive
group ( 34.09%).
Grade I splenomegaly was the second
most common finding in this study which
constituted 43% of total cases. Maximum
number of cases were found i n
inflammatory group (53.48%) followed by
hyperplastic group (20.93%). These
findings were comparable to other
13
studies. The next common grade was
grade III splenomegaly. Inflammatory
spl enomegal y ( 44. 44%) was t he
commonest cause of gr ade I I I
splenomegaly followed by congestive and
neoplastic group .
The l east common gr ade of
splenomegaly in this study was grade IV (4
patients). Commonest cause of grade IV
splenomegaly was neoplastic (50%)
followed by inflammatory and hyperplastic
group (25%) each. Out of the 2 neoplastic
cases of grade IV splenomegaly, one was a
case of chronic myeloid leukaemia (CML)
and the other, of hairy cell leukaemia. The
inflammatory cause of grade IV spleen was
hepatitis C causing cirrhosis, and the
hyperplastic cause was autoimmune
haemolytic anaemia. In a study, the
c ommone s t c aus e s of mas s i v e
splenomegaly were hyperreactive malarial
splenomegaly (29.2%), chronic myeloid
leukaemia (CML-25%), NCPF (12.5%) and
2
cirrhosis (12.5%). In another study by
O'Reilly et al, important causes of massive
splenomegaly were liver cirrhosis (28.6%),
myelofibrosis (22.9%), CML (14.3%) and
20
lymphoma(14.3%). In a French series,
common causes were lymphoma (38.3%),
chronic lymphocytic leukaemia (23.4%)
21
and hairy cell leukaemia(10.6%).
In the present study, there were 2
cases where the cause of splenomegaly
r e ma i ne d o bs c ur e de s pi t e a l l
i nv e s t i gat i ons . Bot h had mi l d
splenomegaly (grade I); no abnormality
16 Bombay Hospital Journal, Vol. 54, No. 1, 2012
was detected in their bone marrow study,
liver biopsy, and endoscopy. The
splenomegaly in them was labelled as
"Splenomegaly of Indeterminate origin."
In a few cases in present study,
multiple aetiologies could be attributed,
such as hepatitis B and C causing liver
cirrhosis, portal hypertension. For sake of
statistics, these were grouped into
inflammatory causes. Multifactorial
aetiology has been seen in a study by
19
Konan et al although this study was done
on children.
In the present study moderate to
severe anaemia was found in 49 cases
(49%). Severe anaemia was more common
in females. Severe anaemia was most
commonly seen in hyperplastic group
(61.53% ). Next cause of severe anaemia
was neoplastic group with 30.76%
patients. There was no correlation
between splenic size and degree of
anaemia as was seen in a study by
22
Hussain et al.
Peripheral smear findings helped the
course of investigations in this study as in
1,2
other studies. Bone marrow was done in
17 patients, which was informative and
di agnosti c. Out of 17 pati ents,
haematologic malignancies (neoplastic)
were diagnosed in 7 cases (41.17%). 7
patients had findings of anaemia
( 41. 17%) , wi t h di morphi c bei ng
commonest, (3 out of 7 cases, 42.85%). In
a study by Ali et al, haematological
malignancies constituted 37% of adult
s pl e no me g al y , but t hat s t udy
concentrated on haematological causes of
23
splenomegaly only. Ultrasound was a
good way of confirming splenomegaly and
diagnosing the aetiology. Ultrasonography
can measure even a low to mild degree of
splenic enlargement and therefore should
be useful in assessing splenomegaly
24
rates.
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