|Ahead of print publication
A hospital-based prospective study of sickle cell disease in children of Eastern India
Bighneswar Senapati1, Bharati Das1, Sarbeswar Pradhan2, Arakhita Swain1, Aryan Jaiswal3, Nirmal Kumar Mohakud2
1 Department of Pediatrics, Sriram Chandra Bhanj Medical College and SVPPGIP, Cuttack, Odisha, India
2 Department of Pediatrics, Kalinga Institute of Medical Sciences, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
3 Department of Biotechnology, Kalinga School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
|Date of Submission||06-Oct-2021|
|Date of Decision||08-Dec-2021|
|Date of Acceptance||08-Dec-2021|
Nirmal Kumar Mohakud,
Department of Pediatrics, Kalinga Institute of Medical Sciences, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Background: Sickle cell disease (SCD), sickle cell anemia (SCA), and sickle beta-thalassemia (SBT) are due to a mutated gene of hemoglobin (Hb), which makes the red blood cells sickle-shaped and decreases their oxygen-carrying capacity. The disease is prevalent in the rural population of Odisha. Clinical presentation of SCA and SBT is similar, though there is a difference in treatment modality for both the entities. However, there are a few studies to delineate between these two diseases in children below 15 years. Aim: A hospital-based prospective study was conducted in eastern India to assess the clinicohematological profile of children with SSA and SBT. Methods: The prospective study was conducted in Srirama Chandra Bhanja Medical College, Cuttack, Odisha, from January to December 2020. A total of 43 confirmed cases by Hb electrophoresis of SCD were enrolled. Detailed clinical manifestations and hematological and biochemical tests were recorded as per the pro forma. Results: Clinical findings validated the major manifestations of SCD as splenomegaly, hepatomegaly, jaundice, fever, abdominal pain, crisis, and myopathy. Most of the SCD patients have severe anemia (range; 2.7–12.4 g/dL) at presentation. Splenomegaly was found in 43.8% of SCA versus 85.2% of SBT cases. Jaundice was more marked in SCA (62.5%) compared to SBT (48.1%) cases. Both the mean corpuscular Hb and mean corpuscular volume are more in SCA compared to SBT. Conclusions: Presentation of SCA is more severe compared to SBT. Enhanced implementation of newborn screening programs in Odisha state will help in reduction of the disease burden and morbidity due to SCD.
Keywords: Children, hemolytic anemia, sickle cell anemia, sickle cell disease, sickle β-thalassemia
|How to cite this URL:|
Senapati B, Das B, Pradhan S, Swain A, Jaiswal A, Mohakud NK. A hospital-based prospective study of sickle cell disease in children of Eastern India. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 6]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=343056
| Introduction|| |
Sickle cell disease (SCD) refers to a category of inherited hemoglobin (Hb) disorders. The pathophysiology of sickle Hb (HbS) variant emerges from the polymerization of the ensuing HbS variant, which triggers a chain of erythrocyte alterations and the disorder is known to be caused by a single-nucleotide substitution at position 6 of the globin gene. Both acute and chronic sequelae cause significant morbidity in people with sickle cell anemia (SCA). The most serious cases can be devastating within the first few years of life if they are not treated effectively.
The principal pathophysiology is focused on deoxyHbS polymerization and the development of long fibers within red blood cells (RBCs), resulting in a twisted sickle shape, which contributes to intensified hemolysis and sickle red cell vaso-occlusion. The clinical appearance of SCD patients, on the other hand, is incredibly complicated, and many events can lead to vaso-occlusion. Recent research has demonstrated the significance of red cell dehydration, irregular RBC attachment to the vascular endothelium, inflammatory events, stimulation of all cells in the vessel, and nitric oxide metabolism disorders in the pathophysiology of this multi-organ disease. Hb E-thalassemia and sickle-cell anemia are two other common Hb disorders that have been confirmed to be widespread in India.
In India, SCD is common among all ethnic groups, with a particularly high prevalence among the tribal population. Odisha has the highest incidence of SCD in India, followed by Assam, Madhya Pradesh, Uttar Pradesh, Tamil Nadu, and Gujarat. In India, the average frequency of SCD is 4.3%, and in Odisha, it is 9.1%. Since neither SCA nor sickle beta-thalassemia (SBT) is uncommon in the eastern part of India; hence, a large-scale community-based study is needed to measure the exact incidence in the population. A hospital-based prospective study was conducted to evaluate the epidemiology and clinical presentation of this disease in children under 15 years of age.
| Methods|| |
The prospective study was conducted on 43 children aged <15 years whose Hb electrophoresis was consistent with SCA or SBT and were admitted to Srirama Chandra Bhanja Medical College and Hospital (SCB-MCH) and Sardar Vallabhbhai Patel Post Graduate Institute of Paediatrics, Cuttack, Odisha, from January to December 2020. Any other hemoglobinopathies were excluded from the study. Various clinical, hematological, and biochemical tests were carried out in the enrolled patients during treatment, and data were collected and further analyzed. The institutional ethical clearance from SCB-mean corpuscular hemoglobin (MCH) (Appln. No: 57/07/02/2020) was obtained before the study. Written consent to participate in the study was obtained from the guardian/family members.
Anthropometry, general and systemic examination, particularly gastrointestinal system, detailed medical history of patients, and frequency of blood transfusion were obtained.
Complete blood count, including RBC count, Hb count, mean corpuscular volume (MCV), MCH count, reticulocyte count, total platelet count, erythrocyte sedimentation rate (ESR), and the total leukocyte count, was done in all enrolled patients.
Liver function test, i.e., serum bilirubin, serum glutamic-oxaloacetic transaminase, and serum glutamic-pyruvic transaminase, renal function test (serum urea and serum creatinine), and serum ferritin tests were carried out in all patients.
The data obtained were analyzed according to categorical variables in the form of percentage of incidence rates in the patients.
| Results|| |
Out of total of 43 cases, SBT constitutes 27 (67%) of all cases. There was a male predominance (Male: Female; 3.3:1). The mean age of patients was 6.8 (range, 1.3–14) years. Most of the patients belong to rural areas, i.e., 75% and 56% of SCA and SBT, respectively.
It was observed that the common manifestations of both SCA and SBT were splenomegaly, hepatomegaly, jaundice, fever, abdominal pain, vaso-occlusive crisis, and myopathy. Pneumonia and hemolytic facies were also observed in these patients.
As shown in [Table 1], splenomegaly was found in 43.8% of SCA cases and 85.2% of SBT cases. Neurological manifestation and chronic leg ulcers were not encountered in the present study; however, two rare cases of delayed hemolytic transfusion reaction (DHTR) were reported.
|Table 1: Clinical manifestations of sickle cell anemia and sickle beta-thalassemia among the 43 sickle cell disease children|
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Unlike splenomegaly, hepatomegaly of varying degrees was seen in 50.5% and 14.8% of cases of SCA and SBT, respectively. Jaundice was detected in 62.5% of cases of SCA and 48.1% of SBT in the present cases. Fever was found in 10 patients (62.5%) of SCA and 19 patients (70.4%) of SBT.
Abdominal pain was manifested in 7.4% of SBT cases in the present study. Hemolytic facies were observed in 12.5% of cases of SCA and 33.3% of cases of SBT. Pneumonia was diagnosed in three patients (18.8%) of the SCA and was caused by Streptococcus pneumoniae. DHTR is found in two patients (12.5%) of SCA in the present series.
The peripheral smear in SCA patients showed mostly normocytic normochromic anemia, and SBT cases showed a microcytic hypochromic picture. [Table 2] depicts that about 78% of cases of SCA had their RBC count ranging from 1.1 to 3.5 million/mm3 with a mean of 3.2 million/mm3, whereas in SBT, 58% of cases had their RBC count ranging within 1.1–3.5 million/mm3 with a mean of 3.3 million/mm3.
|Table 2: The total hemoglobin concentration in blood and red blood cell count in sickle cell anemia and sickle beta-thalassemia-diagnosed children|
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SCD patients have the most severe anemia. As evident from [Table 3], the range of Hb in SCA patients is lying between 2.7 and 12.4 g/dL with a mean value of 6.8 g/dL, whereas in SBT patients, the Hb range was between 2.9 and 10.8 g/dl with a mean value of 6.9 g/dl.
|Table 3: The mean corpuscular hemoglobin in blood and mean corpuscular volume in sickle cell anemia and sickle beta-thalassemia-diagnosed children|
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MCV in SCA patients had normal value, while in SBT, it showed a microcytic picture. Lower ESR value was an incident in the majority of SCA cases (56.8%), ranging in between 1 and 10 mm in 1st h. In SBT, the ESR ranges from 2 to 7 mm in 1st h (mean, 3.9 mm), as shown in [Table 4]. Peripheral smear showed variable degrees of anisocytosis, poikilocytosis, anisochromia, and polychromasia in all the cases of SCD. Target cells and sickled cells were seen to a variable degree in both SCA and SBT.
|Table 4: The erythrocyte sedimentation rate and reticulocyte count of blood taken from sickle cell disease and sickle beta-thalassemia-diagnosed children|
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In the present study, 71% of SCA patients and 67% of SBT patients showed an elevated level of serum bilirubin, as shown in [Table 5]. Five cases of SCA and six cases of SBT were transfused within the period of study. Two cases of SCA with low Hb are diagnosed with DHTR. They were managed with injectable steroids. The Hb level improved and they did not require transfusion.
|Table 5: The total bilirubin count in serum extracted from sickle cell anemia and sickle beta-thalassemia-diagnosed children|
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| Discussion|| |
Major group of SCD belongs to the SBT type (67%). Although SCA and SBT mostly presented with anemia, the severity is more marked among an SCA group. Both entities cause various organ involvement, but hepatitis and pain abdomen were prominent among SCA cases. However, SBT cases typically can be differentiated by the microcytic picture of the peripheral smear.
Diagnosis of sickle cell disease is based on analysis of Hb. Typically, this analysis involves protein electrophoresis or chromatography, which are cheap techniques and widely available worldwide, although Hb mass spectrometry and DNA analysis are being increasingly used because these techniques enable high-throughput testing. The increased incidence of SBT can be attributed to better detection facilities with high-performance liquid chromatography and Hb electrophoresis. The clinical manifestations of SCD are caused due to intracellular polymerization of the HbS molecule. In hypoxic conditions, the HbS molecule is deoxygenated, causing polymerization and resulting in loss of erythrocyte flexibility. Repeated cycles of oxygenation and deoxygenation cause irreversible membrane damage and formation of sickled cells. The sickled erythrocytes are less definable, thus resulting in microvascular occlusion and hemolytic anemia, which are typical of the disease.,
From the obtained results, it was found that the common manifestations of SCA were splenomegaly, hepatomegaly, fever, abdominal pain, fever, crisis, pneumonia, and myopathy. Acute splenic sequestration further leads to splenomegaly which is characterized by a tender, rapidly enlarging spleen due to the accumulation of sickle erythrocytes and other blood constituents and may lead to shock due to loss of effective circulating volume. Jaundice appeared as a sign for SCD chiefly due to increased levels of indirect reacting bilirubin, which is due to excessive hemolysis of RBCs. The cause of the fever can be attributed to infection and tissue necrosis during the painful crisis. Bacterial infections are a main cause of morbidity and mortality in children diagnosed with SCD. Several organisms, including S. pneumoniae, Haemophilus. influenza, and nontyphi Salmonella More Details species, have been identified as important causes of infection. The increased susceptibility of affected children is likely to result from several causes, including impaired splenic function, defects in complement activation, micronutrient deficiencies, and tissue ischemia. The normal RBC count is 4.5 million/mm3 of blood; however, in SCD, the RBCs are kept on destroying, and the total RBC count of SCD patients is usually less than the normal people. The SCA may be superimposed with iron and folic acid deficiency, giving rise to a macrocytic and microcytic picture observed in the present series. The lower MCH and MCV levels are likely to diminish the amount of intravascular sickling, and this reduction is reflected in the lowered βS gene expression associated with β thalassemia in sickle cell heterozygous. The ESR value depends on the constituent of plasma, number, and shape of RBCs. As sickled RBCs are unable to form rouleaux, low ESR is observed in the majority of SCD cases. The situation of hyperbilirubinemia is also observed in SCD patients, which is caused due to the excessive hemolysis of RBCs.,
In two cases of SCA, there were features of DHTR which have been managed successfully with injectable steroids. Unlike SCA, SBT patients were manifested with splenomegaly at a higher rate (85.2%). The other symptoms were similar to that of SCA except that they were less severe in nature. The anemia presented in SBT as evidenced by the RBCs count and the Hb level was less severe in comparison to that of SCA. The peripheral blood picture in SBT was found to be microcytic and hypochromic, whereas that in the SCA, it was normocytic and normochromic. This was derived by RBC indices where MCH and MCH concentration, both, were found to be low in comparison to that in the SCA. Low ESR value, increased reticulocyte response, and leukocytosis are observed in patients of both SCA and SBT. Biochemical evidence of hyperbilirubinemia, relatively normal renal function tests, normal liver function test, and a normal serum ferritin level was elicited in both the series of SCA and SBT. It is also realized that since neither SCA nor SBT is uncommon in this part of the state, a large-scale community-based study is needed to measure the exact incidence in the population.,
As it is a hospital-based study, the number of cases is less, which may not be representative of the whole community; however, the study was conducted by the apex hospital by the state, where patients from all over the states are coming. Hence, the values presented are almost the reflection of cases being encountered in the eastern India.
| Conclusions|| |
Presentation of SSA is more severe compared to SBT. Enhanced implementation of newborn screening programs in Odisha state will help in the reduction of disease burden and morbidity due to the SSD. SSD cases need premarriage counseling to prevent disease spread and genetic counseling to help them make informed reproductive decisions and have healthy children, with preventive programs available when appropriate.
We acknowledge our sincere thanks to Dr. Mirabai Das, MO, KISS university, for her technical support in preparing the manuscript. We are obliged to all parents and children for their support to carry out the work. We greatly acknowledge our sincere gratitude to the colleagues for their insightful advice during the whole process of research work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]