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ORIGINAL ARTICLE
Post Splenectomy Outcome in β-Thalassemia
Rashid H. Merchant
1
&Ami R. Shah
1
&Javed Ahmad
1
&Alka Karnik
2
&Nooralam Rai
3
Received: 12 October 2014 /Accepted: 13 May 2015
#Dr. K C Chaudhuri Foundation 2015
Abstract
Objectives To evaluate changes in annual blood transfusion
requirements and complications after splenectomy in patients
with β-thalassemia.
Methods Forty post-splenectomy β-thalassemic patients aged
8–33 y, receiving regular blood transfusions and chelation
therapy were included and non transfusion dependant patients
were excluded from this retrospective cross-sectional study.
Details about their surgery, transfusion requirements, and
platelet levels were recorded on a standard proforma. All pa-
tients underwent a B-mode and color-coded duplex sonogra-
phy of the hepatoportal system during the study period.
Results The average ferritin level in the year prior to the study
was 4432 mcg/L (range 480–12,200 mcg/L). The annual
bloodtransfusionrequirementinthefirstyearand5ypost
splenectomy [mean± SD (138.41 ± 90.38 ml/kg/y); (116±
41.44 ml/kg/y)] were significantly different from require-
ments before splenectomy [(mean± SD) 294.85±226 ml/kg/y;
pvalue <0.001]. There was a significant rise in platelet counts
within 24 h post splenectomy with a mean rise of 4,51,000/
mm
3
(pvalue<0.001). During the follow up period, infections
were noted in 50 % of patients, with malaria (18.75 %) being
the most common. Doppler study of the portal system in one
case showed portal vein thrombosis.
Conclusions A significant sustained fall in annual blood
transfusion requirement and a rise in platelet counts occurred
post-splenectomy. Increase in annual blood transfusion re-
quirement should be investigated to find the cause.
Keywords Thalassemia .Post-splenectomy .
Complications .Transfusion requirements .Splenunculi
Introduction
β-thalassemia remains a significant health problem through-
out the world, particularly in India, with blood transfusion and
iron chelation being the mainstay of its management. The
excessive destruction of RBCs and extra-medullary hemato-
poiesis cause splenomegaly which increase the transfusion
requirement [1]. Splenectomy is often performed to avoid this
complication, thus reducing the frequency of blood transfu-
sions [2]. The introduction of regular blood transfusion and
quality iron chelation has resulted in a decrease in extra-
medullary erythropoiesis and the number of non-functional
RBCs which would otherwise be destroyed by splenic tissue.
With optimum management, splenomegaly and its side effects
appear late, usually delaying the need for splenectomy until
the second decade. Splenectomy is known to be associated
with short and long term complications such as infections,
hypercoagulability, and thromboembolism [3]. Recurrence
of anemia may occur due to the presence of splenunculi which
enlarge following splenectomy, therefore it is necessary to
detect and remove them during surgery.
Material and Methods
This retrospective cross-sectional descriptive study was con-
ducted in the Department of Pediatrics at Nanavati Super
Speciality Hospital between January 2012 and January 2013.
Forty post-splenectomy β-thalassemia patients aged 8–33 y
on regular transfusion and chelation therapy attending the
*Rashid H. Merchant
deandoc2000@hotmail.com
1
Department of Pediatrics, Nanavati Super Speciality Hospital, Vile
Parle (W), Mumbai 400056, Maharashtra, India
2
Department of Radiology, Nanavati Super Speciality Hospital,
Mumbai, India
3
Department of Pediatrics, New York Methodist Hospital, New
York, NY, USA
Indian J Pediatr
DOI 10.1007/s12098-015-1792-5
Thalassemia clinic, were included in the analysis. Non trans-
fusion dependant thalassemics were excluded from the study.
A detailed history including documented infections,
hospitalisations and pre- and post-splenectomy platelet counts
and transfusion requirements were collected from patient re-
cord books. For the purpose of the study, those with thrombo-
cytopenia (< 1,00,000 cells/mm
3
), increased transfusion re-
quirement (> 220 ml/kg/y) with or without splenomegaly were
considered as having hypersplenism. USG colour Doppler
was undertaken during the study period by an experienced
sonologist to assess portal venous circulation and the presence
of splenunculi; liver size was not evaluated.
Results
The mean age of the 40 patients was 21.5 y (range 8–33 y), of
which 16 (40 %) were below age 20, 14 (35 %) between 20 to
25 and 10 (25 %) above 25 y of age. There were 27 (67.5 %)
males and 13 (32.5 %) females. The average ferritin level in
the year prior to the study was 4432 mcg/L (range 480–12,200
mcg/L). The mean age at splenectomy was 14 y and median
follow up duration was 7 y (mean 7.5 y). The most common
indication for surgery was hypersplenism (60 %) followed by
increased transfusion requirement (25 %) and massive spleno-
megaly (crossing umbilicus) (15 %). In this study 31 (77.5 %)
patients were on prophylactic oral penicillin, 26 (65 %) were
vaccinated 6 wk prior to splenectomy (i.e., pneumococcal,
Haemophilus influenzae type b and meningococcal), while
the vaccination status of 14 patients was unavailable.
The annual transfusion requirements to maintain a target
hemoglobin of 9 g/dl decreased after splenectomy in 33
(82.5 %) whilst there was no change in 7 (17.5 %) patients.
The mean annual blood transfusion requirement presurgery
was 294.85±22.6 ml/kg/y, which decreased significantly to
138.41±90.38 ml/kg/y (pvalue <0.01) post surgery, demon-
strating a 43 % fall in transfusion requirements. In 28 (70 %)
patients splenectomised for more than 5 y the transfusion
requirements were still lower than presplenectomy require-
ments, though 11 of them demonstrated an increase as com-
pared to requirements in the 1st year post-splenectomy
(Table 1).
The pre splenectomy platelet counts ranged from 30,000–
4,00,000 cells/mm
3
(mean 1,44,564 cells/mm
3
) whereas 24 h
post splenectomy, counts ranged from 1,86,000–12,00,000
cells/mm
3
(mean 5,91,230; p0.001) with a mean rise of 4,
51,000/mm
3
. Aspirin prophylaxis was given in 10 patients.
Two patients suffered from thrombotic complications, 2 and
5 y after splenectomy and required long term anticoagulation
with warfarin; one had a portal vein thrombosis and the other
had a cerebral arterial thrombosis. Other vascular complica-
tions like pulmonary artery hypertension could not be
evaluated.
In the present study 50 % individuals suffered from infec-
tions although none developed sepsis following the procedure
or during the follow up period. Malaria (Plasmodium
falciparum and P. v i v a x ) was the most common infection doc-
umented (18.75 %). Other forms of infections included, ab-
scess (8.33 %), pneumonias (4.16 %), sepsis (4.16 %) and
unspecified (23 %). The abscesses were subcutaneous, tonsil-
lar and osteomyelitis. Microbiological isolation data was un-
available in most cases, therefore the causative organism
could not be evaluated.
Hepato-portal ultrasound and doppler studies were done
after a mean interval of 7.5 y post-splenectomy and demon-
strated portal vein thrombosis with portal cavernoma in one
patient. Splenunculi were detected in 2 patients; of these, one
patient showed a rise in annual blood transfusion requirements
on follow up whereas the other continued to have lower trans-
fusion requirements 5 y post surgery.
Discussion
At the current time splenectomy is not recommended as a
standard procedure in thalassemic individuals but is often
Tabl e 1 Difference in annual blood transfusion requirements (ml/kg/y) pre splenectomy, post splenectomy, and after 5 y
Difference in annual blood transfusion requirements Paired differences T Df Significance
(2-tailed)
Pvalue
Mean
(ml/kg/y)
SD SEM 95 % Confidence Interval of the Difference
Lower Upper
Pre & immediate post splenectomy 156.44 201.51 31.86 91.99 220.89 4.91 39 .000
Pre splenectomy & 5 y after splenectomy 194.34 249.65 47.18 97.53 291.14 4.11 27 .000
Immediate & after 5 y post splenectomy 27.84 99.82 18.86 −10.86 66.54 1.47 27 .152
SD Standard deviation; SEM Standard error of mean; TTscore;Df Degree of freedom
There was a significant change in annual blood transfusion requirements post splenectomy which was maintained 5 y later. The difference between
requirements in the first year and beyond 5 y post splenectomy is not significant (p0.152) which shows that the effect onannual blood transfusion rate is
maintained for long periods
Indian J Pediatr
indicated in suboptimally transfused patients, as its removal
increases RBC survival thus decreasing transfusion require-
ments [4,5]. Few Indian studies have documented the long
term efficacy of splenectomy [2,6].
Splenectomy is avoided in children below the age of 5 y as
the risk and severity of postsplenectomy sepsis and complica-
tions are high [4,7].Twopatientsinthegroupwere
splenectomised before 5 y of age (at 2 and 3 y respectively)
for massive splenomegaly, however they did not develop any
major infections. Hypersplenism, defined as anemia, throm-
bocytopenia and neutropenia with or without splenomegaly,
may be the result of suboptimal transfusion in the first decade
of life. It was the commonest indication (60 %) for surgery in
the present series in accordance with other studies [8,9].
Several studies have demonstrated a fall in the transfusion
requirement to < 150 ml/kg/y immediately after splenectomy
[9,10]. In the present study the annual blood transfusion re-
quirement decreased significantly in 82.5 % patients after
splenectomy (pvalue <0.01) and the difference was main-
tained after 5 y (pvalue <0.01). This is similar to the study
conducted by Cohen et al. [10] which showed that transfusion
requirements remained stable after the predictable fall in the
first year post surgery, thus reducing hospital visits and im-
proving quality of life [10]. Porecha et al. demonstrated a fall
in transfusion requirements post splenectomy along with bet-
ter quality of life due to improved hemoglobin in Indian thal-
assemics [6].
With multiple studies demonstrating the long term effect of
splenectomy in reducing transfusion requirements, it is impor-
tant to recognize and investigate any rise in annual blood
transfusion requirements. A search for an etiology may reveal
red cell alloimunisation, accessory spleens, or other causes of
increased red cell destruction such as infections [10]. The
present study had 11 (27.5 %) thalassemics with increase
(mean 45.23±46.23 %) in transfusion requirements on
followup compared to the immediate post surgery require-
ments and one of them showed multiple splenunculi on ultra-
sound examination.
Congenital or acquired accessory splenic tissue can be re-
sponsible for a rise in transfusion requirements in
splenectomised thalassemics [11,12]. The congenital variety
known as splenunculi are present in 10–30 % of the popula-
tion and are usually located near the hilum of spleen [13].
They are known to have the same structure and function as
the spleen and may contribute to the increased transfusion
requirement and hypersplenism; hence it is essential to detect
and remove them during splenectomy [12]. These have to be
differentiated from splenosis, which is seeding of splenic tis-
sue in the peritoneum after trauma or surgery [13].
Red cell alloimmunisation occurs in transfusion dependant
thalassemics through different mechanisms. Patients who
have a splenectomy have higher rates of alloimmunization
when compared to patients without splenectomy. One possible
mechanism is that altered deformity profiles of RBCs in
splenectomised patients may expose new antigens which pro-
mote an immune response [14,15]. Thus an active search for
antibodies is required for maintaining transfusion efficacy.
Infections are common adverse effects of splenectomy, as
the spleen plays an important role in eradicating infections
from the body. In addition, several organisms thrive in envi-
ronments with high iron content (e.g., Yersinia enterocolitica)
[8]. Overwhelming post-splenectomy infection (OPSI),
though more common in children and within the first few
years after surgery, is not uncommon in adults [16]. None of
the index patients developed OPSI. In the literature, incidence
of infection after splenectomy is 3.2 % with a mortality rate of
1.4 % [17], however the present study did not document any
severe infections.
Malaria was the most common infection (18.75 %) in the
index patients. Earlier studies have also documented increased
incidence of malaria in βthalassemia patients [18]. The asso-
ciation is explained by predilection of Plasmodia for reticulo-
cytes and naïve erythrocytes along with factors like frequent
blood transfusions and splenic dysfunction [19]. Although the
spleen is known to take part in red-cell re-modeling, parasite
clearance, and immune functions in malarial infection [20], its
role in protection against the disease is still unclear. The ab-
sence of a spleen is generally believed to be associated with
more severe infections, particularly of P. falciparum malaria
[17].
Current guidelines recommend immunisation with pneu-
mococcal, Haemophilus influenzae type b, and meningococ-
cal vaccines 4–6 wk prior to surgery, however only 77.5 % of
children received these immunizations in the index study.
Postsplenectomy prophylaxis with penicillin, or erythromycin
for individuals allergic to penicillin, protects against infections
and is recommended for life [4].
Splenectomy results in a hypercoagulable state by permit-
ting the circulation of greater numbers of red cells with altered
membranes, and an increase in the number of platelets.
Thrombocytosis develops in 75 % of splenectomised patients,
and in 15 % it reaches 1,000,000 cells/mm
3
or more, platelet
levels typically peak between 1 wk and 4 mo after splenecto-
my [21]. In our series there was a significant rise in platelet
counts (pvalue < 0.01). Aspirin was started in 10 patients with
persistent platelet counts above 1,000,000 cells/mm
3
. Platelet
adhesion and function tests were not evaluated. There is a lack
of comprehensive evidence on the role of antiplatelet or anti-
coagulant agents, however, studies have documented lower
recurrence rate of thrombotic episodes in patients on aspirin
[22]. The association of higher platelet counts with thrombotic
complications further indicates a role for aspirin [23].
The hypercoagulable state predisposes these individuals to
an increased risk of thrombotic complications [24,25]. A
recent study demonstrated that thromboembolic events oc-
curred in 1.65 % of 8860 thalassemic patients with a
Indian J Pediatr
predilection for splenectomised patients [22]. Pulmonary hy-
pertension and portal vein thrombosis are also documented in
this population [24]. Doppler may be a useful screening tool in
splenectomised children with thalassemia to detect portal vein
thrombosis [26].
Conclusions
Splenectomy is a necessary evil for many thalassemia patients,
although it imparts certain risks. New surgical techniques and
better understanding of ideal postoperative and preventive
measures have improved the outcome. The present cross-
sectional study attempts to highlight the different benefits
and complications which reflect the outcome of thalassemics
after splenectomy. It is concluded that splenectomy, which is
no longer a favored choice of treatment in thalassemia patients
results in a significant and sustained fall in blood transfusion
requirements, however increase in transfusion requirements
may warrant search for other causes such as accessory splenic
tissue. The authors observed that thrombocytosis is a known
consequence of splenectomy. A prospective study with long
term follow up and analysis of the quality of life is needed to
quantify the parameters evaluated in this study.
Contributions RHM: Concept, design of the study and reviewed the
final draft; ARS: Conducted the study, data collection and interpretation,
drafted the manuscript; JA: Data interpretation and drafted the manu-
script; AK: Ultrasound examination and interpretation; NR: Reviewed
the manuscript. RHM will act as guarantor for this paper.
Conflict of Interest None.
Source of Funding None.
References
1. Kumar V, Abbas AK, Fausto N. Robbins and cotran pathologic
basis of disease. 7th ed. Philadelphia: Elsevier Saunders; 2005. p.
633–4.
2. Chaudhuri N, Samanta N, Bose S, Maity CR. Prospect of splenec-
tomy in thalassemia. Indian Pediatr. 1994;31:988–91.
3. Pecorari L, Savelli A, Cuna CD, Fracchia S, Borgna-Pignatti C. The
role of splenectomy in thalassemia major. An update. Acta Pediatr
Mediterr. 2008;24:57–60.
4. Cappellini MD, Cohen A, Eleftheriou A, Piga A, Porter J, Taher A.
Guidelines for the Management of Transfusion Dependent
Thalassaemia. 3rd ed. Nicosia: Thalassemia International
Federation; 2014. p. 126–32.
5. Handin RI, Lux SE, Stossel TP. Blood: principles & practice of
hematology. 2nd ed. Philadelphia: Lippincott Williams &
Wilkins; 2003. p. 650–2.
6. Porecha MM, Udani D, Mehta V, Gami A. Splenectomy in man-
agement of thalassemia major - a boon for the little Angel. Internet J
Surg. 2010;24:1.
7. Hawsawi ZM, Hummaida TI, Ismail GA. Splenectomy in thalas-
saemia major: experience at Madina Maternity and Children’s
Hospital, Saudi Arabia. Ann Trop Paediatr. 2001;21:155–8.
8. Zarina AL, Norazlin KN, Hamidah A, Aziz DA, Zulkifli SZ, Jamal
R. Spectrum of infections in splenectomised thalassaemia patients.
Med J Malaysia. 2010;65:284–6.
9. Al-Salem AH, Nasserulla Z. Splenectomy for children with thalas-
semia. Int Surg. 2002;87:269–73.
10. Cohen A, Gayer R, Mizanin J. Long-term effect of splenectomy on
transfusion requirements in thalassemia major. Am J Hematol.
1989;30:254–6.
11. Riera M, Buczacki S, Khan ZAJ. Splenic regeneration following
splenectomy and impact on sepsis: a clinical review. J R Soc Med.
2009;102:139–42.
12. Mantoro F. Significance of Splenunculi.March 15, 2009. Available
at www.scribd.com/doc/36877282. Accessed on 10 Jan 2013.
13. Mohan H, Amanjit B, Bhardwaj S, Handa U. Splenunculi- report of
three cases. J Anat Soc India. 2002;51:70–1.
14. Ahmed AM, Hasan NS, Ragab SH, HabibSA, Emara NA, Aly AA.
Red cell alloimmunization and autoantibodies in Egyptian
transfusion-dependent thalassaemia patients. Arch Med Sci.
2010;6:592–8.
15. Singer ST, Wu V, MignaccaR, Kuypers FA, Morel P, Vichinsky EP.
Alloimmunization and erythrocyte autoimmunization in transfusion
dependent thalassemia patients of predominantly Asian descent.
Blood. 2000;96:3369–73.
16. Waghorn DJ, Mayon-White RT. A study of 42 episodes of over-
whelming post-splenectomy infection: Is current guidance for
asplenic individuals being followed? J Infect. 1997;35:289–94.
17. Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death
among post-splenectomy patients. J Infect. 2001;43:182–6.
18. Looareesuwan S, Suntharasamai P, Webster HK. Malaria in
splenectomized patients: report of four cases and review. Clin
Infect Dis. 1993;16:361–6.
19. O’Donnell A, Premawardhenac A, Arambepola M. Interaction of
malaria with a common form of severe thalassemia in an Asian
population. Proc Natl Acad Sci U S A. 2009;106:18716–21.
20. Chotivanich K, Udomsangpetch R, McGready R, et al. Central role
of the spleen in malaria parasite clearance. J Infect Dis. 2002;185:
1538–41.
21. Hathirat P, Mahaphan W, Chuansumrit A, Pintadit P, Sasanakul W,
Isarangkura P. Platelet counts in thalassemic children before and
after splenectomy. Southeast Asian J Trop Med Public Health.
1993;24:213–5.
22. Taher AT, Isma’eel H, Mehio G, et al. Prevalence of thromboem-
bolic events among 8,860 patients with thalassemia major and
intermedia in the Mediterranean area and Iran. Thromb Haemost.
2006;96:488–91.
23. Cappellini MD, Musallam KM, Taher AT. Thalassemia as a hyper-
coagulable state. US Oncol Hematol. 2011;7:157–60.
24. Hassan MN, Tahereb GM, Ahmad T, et al. Correlation of splenec-
tomy with portal vein thrombosis in beta-thalassemia major. J Pak
Med Assoc. 2011;61:760–2.
25. Borgna-Pignatti C, Carnelli V, Caruso V, et al. Thromboembolic
events in beta thalassemia major: an Italian multicenter study.
Acta Haematol. 1998;99:76–9.
26. Soyer T, Arbay O. Portal vein thrombosis after splenectomy in
pediatric hematologic disease: risk factors, clinical features, and
outcome. J Pediatr Surg. 2006;41:1899–902.
Indian J Pediatr
