Indian Pediatr 2012;49: 911-913
Sickle Cell Anemia from Central India: A
Dipty Jain, *Khushnooma Italia, Vijaya Sarathi, * Kanjaksha Ghoshand and
From the Department of Pediatrics, Government Medical
College, Nagpur, India; and *National Institute of Immunohaematology,
KEM Hospital Campus, Parel, Mumbai, India.
Correspondence to: Dr Dipty Jain, Professor,
Department of Pediatrics, Government Medical College, Nagpur,
Received: April 13, 2011;
Initial review: May 03, 2011;
Accepted: April 19, 2012.
online: June 10, 2012.
Although sickle cell anemia in India is believed
to have a mild clinical presentation, few studies report severe
disease in many patients from central India. Hence, we have
retrospectively studied 316 children with SCA who were followed up
for a period of 5.8±5.7 years. There were 55.4 blood transfusions,
43.3 episodes of vaso-occlusive crises requiring hospitalization,
and 108.9 hospitalizations per 100 person years. Ninety six (30%)
patients had severe disease whereas 74 patients also fulfilled the
criteria for hydroxyurea therapy. Significant proportion of children
with sickle cell anemia from central India present with severe
clinical presentation and require regular medical attention.
Key words: Sickle cell anemia, Central India, Children.
The prevalence of the sickle
gene in India is found to vary from 2-34% [1,2]. It has often been
stated that sickle cell anemia (SCA) in Indians being linked to the
Arab-Indian haplotype has a mild clinical presentation which goes
unnoticed, sometimes throughout life. This has been attributed to the
high fetal hemoglobin and associated
commonly seen among these patients [3-6]. However, the phenotype of SCA
varies significantly among different population groups of India and
there is limited regional data. In this study we report the clinical
events in sickle cell anemia patients followed up for several years at a
Sickle cell clinic at Nagpur in central Maharashtra where the frequency
of the sickle cell gene is very high among some non-tribal populations.
This retrospective study included children (<18 years
of age) with SCA registered before 2007 at the Sickle Cell Clinic,
Department of Pediatrics, Government Medical College, Nagpur. Only those
patients who had at least one year of follow-up were included in the
study after obtaining a written informed consent from all the patients
and/or their parents. At the time of registration, the sickle homozygous
status of all patients was confirmed by standard procedures. These
patients were followed up regularly the clinic with documentation of all
relevant clinical and laboratory data in a detailed proforma. Clinical
records of these patients were evaluated for clinical events since the
time of registration at the clinic till the last available follow-up or
initiation of hydroxyurea therapy. Appropriate treatment was given as
and when needed. All children with age less than 5 years were offered
penicillin prophylaxis. Patients having any one of the criteria
mentioned in Table I were considered to have severe
disease. Children older than five years, having any one of these
criteria were offered hydroxyurea therapy.
TABLE I Criteria to Define Severe Disease
Frequent vaso-occlusive crisis (³3/year)
Frequent blood transfusion requirement
(³3 per year)
At least one cerebro-vascular event
At least one episode of acute chest
At least one episode of avascular
necrosis of bone
The study included 316 patients (122 females and 194
males) with SCA who were followed up for a period of 5.8±5.7 years
(1832.8 person-years). The median age at presentation was 3.84 years
(range: 15 days to 16 years). There were 1725 hospitalizations in 282
patients (Table II). Severe anemia requiring blood
transfusion was the most common reason for hospitalizations and 1015
blood transfusions were given to 242 children. Majority (62%) of the
blood transfusions were needed when age of the patients was <5 years.
The most common (80%) reason for blood transfusions was severe anemia (hemoglobin
<5g/dL) while the rest were given for stroke, splenic sequestration,
hypersplenism or severe vaso-occlusive crisis (VOC).
TABLE II Clinical Events In Children With Sickle Cell Anemia (N=316)
No. of events per
Median age (y) at
100 person years
Painful crises requiring hospitalization
Severe infection requiring
Moderate episodes of VOC were managed either as
outpatient or on home-basis with analgesics and oral hydration. All
children had at least one episode of painful crisis by 12 years of age.
There were 175 episodes of severe febrile illness requiring
hospitalization including 62 episodes of blood culture proven bacterial
septicemia in 42 patients.
Other common events were splenic sequestration among
26 patients, cerebrovascular accidents among 17 patients, dactylitis
among 14 patients, a vascular necrosis of bone among five patients,
non-bacterial infections like malaria among 14 patients, hepatitis B
among 12 patients, human immunodeficiency virus among three patients and
tuberculosis among three patients. The chronic complications included
sickle hepatopathy among 16 patients and sickle nephropathy among four
patients. Leg ulcer and priapism were seen in only one patient each.
There were 10 deaths which were attributed to severe anemia with hypoxic
encephalopathy among three patients, severe bacterial infection among
two patients, sequestration crises among two patients, tuberculosis with
acquired immunodeficiency syndrome in one patient and unknown reasons in
two patients (home deaths). Ninety six (30%) patients had at least one
criterion to define severe disease among whom 74 children aged >5 years
fulfilled the criteria for hydroxyurea therapy and were treated with
Our study reports a very high incidence of
significant clinical events in SCA children, with 30% patients having
severe disease. A previous study from Nagpur, also reported similar
findings with 1.25 episodes of sickle cell crises and 1.38 episodes of
infections per patient per year in a group of 325 children over a short
period of follow-up (146.84 person-years) . The disease is also
reported to be severe in patients from Orissa [3,8].
A study on tribal patients with SCA from Gujarat
reported lesser number of patients with
³3 painful crises per
year (23.7%) and >3 hospitalizations per year (2.6%) compared to 52% and
16.4% children, respectively in our cohort. The milder disease is partly
attributed to high frequency of a-thalassemia
in them .
Children from central India where the sickle gene is
linked to the Arab-Indian haplotype are stated to have a milder disease
than those with African haplotypes . The cooperative study including
SCA patients with African haplotypes, reported 2.9-49 episodes of
painful crises and 0.0-9.9 episodes of bacteremia per 100 person- years
as compared to 43.3 episodes of painful crises and 3.38 episodes of
bacteremia (despite penicillin prophylaxis) in our study cohort .
Thus, our study cohort had SCA as severe as those with African
Since this is a retrospective analysis of a hospital-
based cohort with documentation of clinical events from the time of
registration at our Sickle cell clinic, we might have missed many events
which would have occurred before their registration. On the other hand,
many patients may still remain undiagnosed while some others might have
died before achieving the diagnosis. The ideal way to understand the
natural history of sickle cell anemia is to undertake neonatal
screening, identify homozygotes and follow them up from birth [9-11].
With the introduction of newborn screening for sickle cell disease in
our hospital since 2010, we have now formed a birth cohort of sickle
cell disease children whom we are following at regular intervals.
Ninety eight percent of the younger children received
penicillin prophylaxis till they reached five years. Still, we report
high rates of bacteremia, 50% of which occurred when children were less
than five years of age. Although 74 patients received hydroxyurea, since
we have included events till the initiation of hydroxyurea, it has no
effect on the number of clinical events considered for the study.
Hydroxyurea was found to be beneficial in our patients with severe
disease (data not shown). To conclude, a significant proportion of SCA
children from central India present with a severe clinical presentation
and require regular medical attention.
Acknowledgement: We thank Dr. Sushma
Gattani for her assistance in compiling the data.
Contributors: DJ diagnosed, managed and followed
all patients, KI drafted the first version of the manuscript, VS
analyzed the data and revised the article, KG and RC helped to confirm
the diagnosis of these patients and critically reviewed the article.
Funding: None; Interests: None stated.
1. Lehman H, Cutbush M. Sickle-cell trait in southern
India. Brit Med J. 1952;1: 404-5.
2. Mohanty D, Mukherjee M. Sickle cell disease in
India. Curr Opin Hematol. 2002;9:117-22.
3. Kar BC. Sickle cell disease in India. J Assoc
Physicians India. 1991;39:954-60.
4. Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR,
Colah RB, Kadam MD, et al. a-thalassemia
on sickle-cell anemia linked to the Arab-Indian haplotype in India. Am J
5. Italia K, Jain D, Gattani S, Jijina F, Nadkarni A,
Sawant P, et al. Hydroxyurea in sickle cell disease — A study of
clinico-pharmacological efficacy in the Indian haplotype. Blood Cells
Mol Dis. 2009;42:25-31.
6. Labie D, Rao S, Dunda O, Dode C, Lapourmeroullie
C, Devi S, et al. Haplotypes in tribal Indians bearing the sickle
gene: Evidence for the unicentric origin of the bs mutation and the
unicentric origin of the tribal populations of India. Hum Biol.
7. Patel AB, Athavale AM. Sickle cell disease in
central India. Indian J Pediatr. 2004;71:789-93.
8. Kar BC, Devi S. Clinical profile of sickle cell
disease in Orissa. Indian J Pediatr. 1997;64:73-7.
9. Redwood AM, Williams EM, Desal P, Serjeant GR.
Climate and painful crisis of sickle-cell disease in Jamaica. Br Med J.
10. Gill FM, Sleeper LA, Weiner SJ, Brown AK,
Bellevue R, Grover R, et al. Clinical events in the first decade
in a cohort of infants with sickle cell disease. CooperativeStudy of
Sickle Cell Disease. Blood. 1995;86:776-83.
11. Miller ST, Sleeper LA, Pegelow CH, Enos LE, Wang
WC, Weiner SJ, et al. Prediction of adverse outcomes in children
with sickle cell disease. N Engl J Med. 2000;342:83-9.