ORIGINAL ARTICLE

JIACM 2005; 6(4): 291-6

Study of Hypersplenism and Effect of Splenectomy on

Patients with Hypersplenism
J Balaji Sundaresan*, TK Dutta**, S Badrinath***, S Jagdish****, D Basu*****

Abstract
Objectives: To determine the occurrence of hypersplenism among patients with splenomegaly, to study its aetiology, and correlate
its severity with the degree of splenomegaly; and to study the response to splenectomy in patients with hypersplenism.
Design of study: A prospective study of adult patients of splenomegaly admitted over a period of ten months.
Setting: Medical wards of a large teaching hospital in South India.
Subjects: 100 adult patients.
Results: One hundred adult patients with splenomegaly were studied. Hypersplenism was observed in 28 patients. The causes of
hypersplenism in them were non-cirrhotic portal fibrosis (9, i.e., 32.2%), cirrhosis of liver (8, i.e., 28.6%), hyper-reactive malarial
splenomegaly (HMS) (7, i.e., 25%) and chronic hepatitis (2, i.e., 7.1%); and a small number of patients formed an idiopathic group
(2, i.e., 7.1%). Though the prevalence of hypersplenism increased with increasing spleen size (p < 0.0001), there was no significant
correlation between splenic size and severity of hypersplenism. Splenectomy, performed in sixteen such patients with
hypersplenism, besides resulting in improvement in cell count of all three haematopoietic cell lines, caused transient leucocytosis
and thrombocytosis in 16 (100%) and 5 (31.25%) patients respectively.
Conclusions: Hypersplenism may be observed in about one-fourth of patients with splenomegaly. Congestive splenomegaly due
to hepatic cause is likely to be the major cause in our setting. All definite cases of hypersplenism are likely to respond to splenectomy,
even with an overresponse in some instances.
Key words: Splenomegaly, Non-cirrhotic portal fibrosis, Hyperreactive malarial splenomegaly, Cirrhosis of liver.

Introduction
Unravelling the cause of splenomegaly in a given case is
often a difficult but fascinating experience. The incidence
and aetiology of splenomegaly is highly dependent on
the geographic locale.
The concept of hypersplenism among patients with
splenomegaly has been known since the eighteenth
century. The criteria to diagnose hypersplenism include
splenomegaly, a peripheral blood picture of anaemia,
neutropenia, and thrombocytopenia (either singly or in
combination), a cellular bone marrow, and significant
improvement in peripheral blood picture following
splenectomy1.
There are very few systematic and planned studies on
hypersplenism.

Aims of this study

1. To determine the occurrence of hypersplenism

among patients with splenomegaly.

2. To study its aetiology and correlate severity of
hypersplenism with the degree of splenomegaly.
3. To study the response to splenectomy in patients with
hypersplenism.

Material and methods

One hundred adult patients of splenomegaly, admitted
consecutively, over a period of ten months in a large
teaching hospital in South India, were included in the
study. Following a detailed physical examination, all
patients were investigated with all or some of the
following investigations, namely, complete haemogram
with reticulocyte count, liver function tests, Widal test,
HBsAg study of blood, bacterial culture of blood, bone
marrow aspiration/biopsy, lymph node biopsy and
ultrasonogram (USG), as warranted by clinical
impression, to confirm the diagnosis. Bone marrow

* Ex-Senior Resident, Department of Medicine, ** Professor of Medicine,

*** Professor of Microbiology and Medical Superintendent, **** Professor of Surgery, ***** Professor of Pathology,
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry - 605 006.

aspiration/biopsy was done in all the patients, whose

haemogram revealed cytopenias. In patients with
history of gastro-intestinal bleed and in patients with
indeterminate splenomegaly (i.e., where the cause was
obscure after performing routine investigations),
additional investigations including gastrointestinal
endoscopy, repeat ultrasonogram of abdomen, and
liver biopsy were done. Estimation of malarial antibody
titre was performed in all patients by indirect
haemagglutination technique using Plasmodium
knowlesi antigen.
Exclusion criteria: Patients with ascites were excluded
from the study.
Hacketts classification of splenomegaly
This classification to assess the degree of splenomegaly has
been accepted by the WHO for usage in malaria surveys,
and can be used for routine clinical examination also2.
Class

Findings on palpation

0.

Spleen not palpable even on deep inspiration.

1.

Spleen palpable below costal margin, usually on

deep inspiration.

2.

Spleen palpable, but not beyond a horizontal line

half way between the costal margin and
umbilicus, measured in a line dropped vertically
from the left nipple.

3.

Spleen palpable more than half way to

umbilicus, but not below a line horizontally
running through it.

4.

Palpable below umbilicus but not below a

horizontal line half way between umbilicus and
pubic symphysis.

5.

Extending lower than class 4.

Hacketts classes 1 and 2 were considered as mild

splenomegaly, class 3 as moderate splenomegaly, and
classes 4 and 5 as massive splenomegaly.
Hypersplenism was diagnosed on the basis of a study
of peripheral blood and bone marrow. The criteria to
d i a g n o s e h y p e r s p l e n i s m i n pa t i e n ts w i t h

292

splenomegaly included a peripheral blood picture of

anaemia, neutropenia, and thrombocytopenia, either
singly or in combination with a cellular bone
marrow1.
Haematological parameters within the following range
were considered normal3:
Haemoglobin: 130 - 180 g/l (13.0 - 18.0 g/dl) (males)
115 - 165 g/l (11.5 - 16.5 g/dl) (females)
Total leucocyte count (TC): 4.0 - 11.0 x 109/l (4,000 - 11,000/
mm3)
Differential leucocyte count (DC):
Neutrophils 2.0 - 7.5 x 109/l (40 - 75%)
Lymphocytes 1.5 - 4.0 x 109/l (20 - 45%)
Monocytes 0.2 - 0.8 x 109/l (2 - 10%)
Eosinophils 0.04 - 0.4 x 109/l (1 - 6%)
Basophils 0.01 - 0.1 x 109/l (0 - 1%)
Platelet count: 50 - 400 x 109/l (150,000 - 400,000/mm3)
Values beyond above ranges (high or low) were
considered abnormal.
Chi square test was used to correlate the degree of
splenomegaly with severity of hypersplenism.
Correlation co-efficient was calculated to correlate the
degree of splenomegaly with various haematological
parameters.
Patients who consented for splenectomy were followedup for a minimum of three months to study the effect of
splenectomy.

Result
There were 38 men and 62 women among 100 patients
of splenomegaly. The male to female ratio was 1:1.6. Of
these 100 patients, 31, 26, and 25 patients were in the
age groups of 20 - 29, 30 - 39, and 12 - 19 years
respectively.
Among 100 patients with splenomegaly, the spleen
size was Hacketts class 1, 2, 3, 4, and 5 in 17%, 31%,
28%, 15%, and 9% patients respectively. The aetiology
of splenomegaly in these patients were as shown in
Table I.

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Vol. 6, No. 4

October-December, 2005

Table I: Aetiology of Splenomegaly in 100 Patients.

Aetiology

Number of patients
(n = 100)

of ultrasonogram, upper gastrointestinal endoscopy, and

characteristic liver biopsy finding of marked
subendothelial thickening of large and medium sized
intrahepatic branches of portal vein with periportal
fibrosis, in presence of a well-preserved liver parenchyma
and hepatic lobular architecture (unlike in cirrhosis of
liver).

Malaria

22

Chronic myeloid leukemia

11

Enteric fever

Non-cirrhotic portal fibrosis (NCPF)

Cirrhosis of liver

Hyper-reactive malarial splenomegaly (HMS):

Hyper-reactive malarial splenomegaly (HMS)

Lymphoma

Iron deficiency anemia

Acute leukemia

Idiopathic

Infective endocarditis

Heart failure

Haemolytic anemia

Prolymphocytic leukemia

Seven patients were diagnosed to have HMS. The

diagnosis was made on the basis of massive splenomegaly,
normal echotexture of liver and portal vein, Kupffer cell
hyperplasia in the liver, features of hypersplenism, raised
levels of malarial antibody, exclusion of other causes of
splenomegaly, and immunological response to
chloroquine4, 5. All the patients of HMS were given
chloroquine 300 mg/week for three months and a fall in
malarial antibody titre was observed on re-estimation at
the end of three months (Table II).

Chronic hepatitis

Systemic lupus erythematosus

Hypereosinophilic syndrome

Budd-Chiari syndrome

Table II: Malarial serology in patients with hyperreactive malarial splenomegaly (HMS) (n = 7).
Patient
Antibody titre
Before treatment
After treatment

Myelodysplastic syndrome

1.

1 : 128

1 : 64

2.

1 : 256

3.

1 : 256

1 : 64

4.

1 : 512

1 : 128

5.

1 : 128

1 : 64

6.

1 : 64

7.

1 : 128

1 : 64

Geometric
Mean titre

1 : 172

1 : 73.48

Hypersplenism
Hypersplenism was found in 28 of these patients of
splenomegaly. The causes of hypersplenism in these
patients were as follows:
1.
2.
3.
4.
5.

Non-cirrhotic portal fibrosis (NCPF) - 9 (32.2%)

Cirrhosis of liver - 8 (28.6%)
Hyper-reactive malarial splenomegaly (HMS) - 7 (25%)
Chronic hepatitis - 2 (7.1%)
Idiopathic - 2 (7.1%)

Larger number of hypersplenism cases was constituted

by conditions like NCPF and cirrhosis of liver (which led
to congestive splenomegaly). Five patients of NCPF and
four patients of cirrhosis of liver had upper gastrointestinal
bleeding.
Non-cirrhotic portal fibrosis (NCPF):
Diagnosis of NCPF in nine patients was made on the basis

Journal, Indian Academy of Clinical Medicine

Chronic hepatitis was diagnosed in two patients on the

basis of abnormal liver function test, positive HBsAg
serology and characteristic liver biopsy finding. In two
patients, cause for splenomegaly could not be found
despite best efforts.
The distribution of different degrees of splenomegaly
among 28 patients with hypersplenism was as follows:
Hacketts class 1 1, class 2 2, class 3 11, class 4 11,
class 5 3. A significant association between increasing

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293

spleen size and occurrence of hypersplenism was found

by using Chi square test (p < 0.0001). However, there were
three patients with mild splenomegaly (Hacketts classes
1 and 2) who had hypersplenism.

dilated portal vein or confluence of collateral vessels at

splenic pedicle as revealed by ultrasonography. On upper
gastrointestinal endoscopy, eleven patients showed
grade II III oesophageal varices, as per standard grading
of varices from I to IV; one patient of cirrhosis of liver
and one patient of NCPF had grade IV varices. In all
patients with portal hypertension, splenectomy was
combined with devascularisation surgery for varices. A
good response with increase in hemoglobin, platelet

No statistically significant correlation was found between

the degree of splenomegaly and haemoglobin level (p =
0.45), total leucocyte count (p = 0.203), or platelet count
(p = 0.440) by calculating the correlation co-efficient,
among the patients with hypersplenism (Table III).

Table III: Correlation of various degrees of splenomegaly with haematological parameters in patients with
hypersplenism (n = 28).
I

II

III

IV

(1)

(2)

(11)

(11)

(3)

4.200

3.500

8.045

5.955

3800

2100

2981

135000

52000

72090

(No. of patients)
Hb (gm/dl)
TLC (/mm3)
Platelet (/mm )
3

Correlation co-efficient

p value

6.167

+ 0.247

0.450

2663

2100

- 0.164

0.203

96727

50333

- 0.029

0.440

Effect of splenectomy

Mean haemoglobin (g/dl)

Of 28 patients with hypersplenism, 16 underwent

splenectomy. This included three cases of HMS and 13
patients of portal hypertension: seven due to noncirrhotic portal fibrosis (NCPF) and six due to cirrhosis of
liver. Patients with portal hypertension had significantly

15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0

10.36
7.5

0.16

count and total leucocyte count occurred in all the

patients (100%) on the first post-operative day. One
patient, however, expired soon after the operation due
to post-operative complications. The response was wellmaintained in all the 11 patients who could be followed
up minimum for three months (Figs. 1, 2, and 3). Four
patients were lost to follow-up.

10.89

11.16

10.88

10.9

1.66

1.66

1.7

1.66

Day 3

Day 5

Day 7

Month 1

10.35
1.48

10.9
1.6

0.0

Pre-op

Day 1

Month 2

Month 3

Time
Fig. 1: Response of haemoglobin to splenectomy (n = 16).

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Vol. 6, No. 4

October-December, 2005

Mean WBC count values in 100s

per cumm

200

168
114

150

158
134

46

123

35

32

100
50
0

26

80
28

71
1.66

13

Pre-op

Day 1

Day 3

Day 5

Day 7

Month 1

Month 2

62
1.66

Month 3

Time
Fig. 2: Response of WBC (n = 16).

400

Mean platelet count in 1,000s per cumm

375
322
300

300

282
241

196

208

268
68

180

225
48

200
134
100

80

71

32
0

Pre-op

Day 1

Day 3

Day 5

Day 7

Month 1

Month 2

Month 3

Time
Fig. 3: Response of platelets to splenectomy (n = 16).

Leucocytosis was observed during the first post-operative

week in all the 16 (100%) patients, with maximal response
on first post-operative day (Fig. 2). The highest count
observed was 28.2 x 109/l. The leucocyte count returned
to normal at the end of one month in all the follow-up
cases. Thrombocytosis was observed in five (31.25%)
patients. Maximal platelet response was observed in an

Journal, Indian Academy of Clinical Medicine

average on seventh post-operative day (Fig. 3). The highest

platelet count observed was 697 x 109/l. However, no
thrombotic complication was observed in any of the
patients. In all the patients, the platelet count became
normal at the end of two months. The peak haemoglobin
levels were observed on fifth post-operative day (Fig. 1).
Maximum rise in the count of all blood cell components

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295

occurred during the first post-operative week.

Discussion
Hypersplenism was observed in 28 of 100 patients with
splenomegaly. Majority (60.7%) of them had splenomegaly
of congestive origin, i.e., due to NCPF and cirrhosis of liver.
Robert O Reilly also found liver disorder as a major cause of
hypersplenism (10 of 35 patients, i.e., 28.6 %) in their series6.
Improvement in all three cell lines occurred in all the 16
(100%) patients who underwent splenectomy in our series
and this was maintained in all of those who were followedup for three months. However, the results of previous
studies on effect of splenectomy, though good, have not
been so overwhelming. Duckett et al reported a positive
response to splenectomy in 88% of their 118 patients with
hypersplenism7 and Letoquart observed a positive
response in 94% of 47 patients8. Both the studies, however,
included many patients with haemoglobinopathies and
haematological malignancies like chronic myeloid
leukemia (CML) and chronic lymphatic leukemia (CLL), in
whom the diagnosis of hypersplenism itself could have
been difficult due to underlying disease.
All our 16 (100%) patients developed leucocytosis
following splenectomy and five patients (31.25%)
developed thrombocytosis. However, both leucocytosis
and thrombocytosis gradually subsided. Our observation
is similar to that of an earlier study by Hirsh et al on 49
splenectomised patients where no thrombotic
complication was observed in any of the patients despite
high platelet count, unless they had persistent anaemia9.
They postulated that anaemia stimulates thrombopoiesis,
and persistent anaemia resulted in various thrombotic
complications in five of their patients. Another study on
post-splenectomy thrombocytosis on 318 patients
revealed thrombocytosis in 75% of the patients after
splenectomy 10 . Nine patients only developed
thromboembolic complications, and four of them had
some underlying malignancy. Thus, it appears some
additional factor contributes to post-splenectomy
thrombotic complications.
Of late, alternatives to splenectomy have been suggested
for hypersplenism. These include splenic embolisation to

296

reduce splenic volume11-13, and transjugular intrahepatic

portosystemic shunt (TIPS) for cirrhotics developing
hypersplenism14.

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Chapman WC, Newman M. Disorders of the spleen. In:

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Ogilvie C, Evans CC. Splenomegaly. In: Ogilvie C, Evans C Eds.

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Duckett JW. Splenectomy in treatment of secondary

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Letoquart JP, La Gamma A, Kunin N, Grosbois B, Mambrini

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Hirsh J, Dacie JV. Persistent post-splenectomy

thrombocytosis and thromboembolism - a consequence
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Journal, Indian Academy of Clinical Medicine

Vol. 6, No. 4

October-December, 2005