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

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)

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 hydroxyurea.

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) [7]. The disease is also reported to be severe in patients from Orissa [3,8].

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 [9]. 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 [10]. Thus, our study cohort had SCA as severe as those with African haplotypes.

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.