Hematological Profile of Sickle Cell Anemia Subjects in Central India: A Cross Sectional Analysis

Introduction Sickle cell disease (SCD), a group of related blood disorders which are caused by sickle hemoglobin (HbS), is clinically one of the most important hemoglobinopathies. It was first recognized as a hematological disorder more than 100 years ago and a molecular disease in 1949.[1] Sickle cell anemia (SCA i.e. SS), the homozygous state for HbS, is the most common and severe form. SCD also includes compound heterozygous states for HbS and other hemoglobinopathies, such as HbC and sickle cell – β thalassemia. The gene for HbS occurs commonly, but not exclusively, in individuals of African ancestry.[2] Sickle cell disease is prevalent in many parts of India including Central India, where the prevalence in different communities has ranged from 9.4-22.2%,[3] and the average frequency of SCD gene ranges between 22 to 44 %.[4] Also 50% of world population of SCD resides in India.[4] .Blood picture in sickle cell anemia is of hemolytic anaemia, characterized by low haemoglobin levels, reticulocytosis, elevated serum levels of lactate dehydrogenase and low serum haptoglobin levels, present in all major forms. A moderately severe normocytic, normochromic anemia manifests in these patients by 3 months of age,[5] and persists throughout life.[6] The hematological profile worsens during the devastating complications clinically manifesting as hemolytic anemia, an increased susceptibility to infections and vaso-occlusion followed by ischemic tissue injury with organ dysfunction and early death.[7]


Introduction
Sickle cell disease (SCD), a group of related blood disorders which are caused by sickle hemoglobin (HbS), is clinically one of the most important hemoglobinopathies. It was first recognized as a hematological disorder more than 100 years ago and a molecular disease in 1949. [1] Sickle cell anemia (SCA i.e. SS), the homozygous state for HbS, is the most common and severe form. SCD also includes compound heterozygous states for HbS and other hemoglobinopathies, such as HbC and sickle cell -β -thalassemia. The gene for HbS occurs commonly, but not exclusively, in individuals of African ancestry. [2] Sickle cell disease is prevalent in many parts of India including Central India, where the prevalence in different communities has ranged from 9.4-22.2%, [3] and the average frequency of SCD gene ranges between 22 to 44 %. [4] Also 50% of world population of SCD resides in India. [4] .Blood picture in sickle cell anemia is of hemolytic anaemia, characterized by low haemoglobin levels, reticulocytosis, elevated serum levels of lactate dehydrogenase and low serum haptoglobin levels, present in all major forms. A moderately severe normocytic, normochromic anemia manifests in these patients by 3 months of age, [5] and persists throughout life. [6] The hematological profile worsens during the devastating complications clinically manifesting as hemolytic anemia, an increased susceptibility to infections and vaso-occlusion followed by ischemic tissue injury with organ dysfunction and early death. [7] Thus current study attempts to report and compares the hematological profile of SCA patients in steady state with other studies in same region.

Materials and Methods
The present cross sectional study was carried out in the Department of Pathology, at a Medical Institute in Central India over the period of one and half years. The hospital of this institute caters to the population residing in the adjoining districts of Central India.

Inclusion criteria:
• Confirmed patients of sickle cell anemia diagnosed by haemoglobin electrophoresis and HPLC.
• Informed consent was sought from all cases.
Exclusion criteria: • Patients with history of complications in past two years. All statistical analysis was done after recording the complete data on Excel worksheet.

Result
A total 65 SCA patients in steady state attending OPD during the study period were included. There were 31 males and 34 females ( Table 1) with age ranging from 11 months to 43 years. Maximum number of males (n=9) as well as females (n=12) were seen in 13-20 years age group ( Table 1). The age and sex related changes in the hematological parameters of SCA patients are documented in Table 2. Average Hb observed in males and females was 8.93±2.11gms/dl and 8.05±1.88 gms/dl respectively ( Table  2). Steady rise in hemoglobin levels with increasing age are recorded in both genders till the fourth decade; in fifth decade slight fall in the hemoglobin is seen both sexes. Least average hemoglobin is seen in females of age upto 5 years (6.2± 1.5gms/dl).

Discussion
The importance of baseline haematological values of any patient of sickle cell disease lies in their use in monitoring the status and management of these patients. Also chronic normocytic normochromic hemolytic anemia is the typical finding in SCA. This study has more number of female subjects (n=34) than male (n=31). Maximum patients are in   13-20 years age group followed by 21-30 years age group.
No patients are more than 50 years, may be due to apathy towards them which may be due to economic constrains, other reason may be death before reaching this age.
Total hemoglobin is low in all SCA patients, possibly on account of chronic hemolysis. In comparison to other studies in this region, the average value is less than that reported in Gadhchiroli region, [8] but more than that reported by other two, [9][10] as seen in Table 3. By 10 to 12 weeks of age mild hemolytic anemia is apparent in SCA. [11][12] Here, in the first five years of life clinically moderate anemia was seen in both genders. Lower level of hemoglobin seen in age upto 12 years could be due to additional nutritional requirement in childhood and recurrent infections along with pre existing mild hemolysis. Rapid increase in hemoglobin was noted afterwards till 40 years age. In males it may be due to enhancing effect of testosterone on hematopoiesis, as there is increase in the level of this hormone with onset of puberty. In females it may be due to increasing awareness for nutrition and medical attention in child bearing age group. The age wise changes in hemoglobin are similar to Shrikhande et al, [10] and those in females are similar to Hayes et al. [13] The average RBC count is higher, and lower than one study each. The average hematocrit is found similar to, [8] and higher than one other work. [9] As expected, the hematocrit, MCV, MCH and MCHC are higher in males than females.
Overall MCV is similar to other studies of this region, [9][10], [14] except one. [8] Observations of decreased MCV are also there, justified by concurrent iron deficiency. [15][16] Increased MCV has also been reported. [13] This may be owing to increased requirement of folate due to hemolysis and concurrent folate deficiency. Thus attention towards proper nutrition and supplementation of folate, and iron if required, is re-emphasized. Other RBC indices, increased RDW and Reticulocyte count are more or less similar to other works. These are indicative of ongoing hemolysis, increased production of young RBCs. Platelet count, TLC and Gran% are found normal, indicating their changes might suggest complications. Thrombocytosis was found in steady state by a few, similar to increased TLC. [17][18] As there are few differences in the hematological findings in the SCA patients found in studies from Central India, larger scale work with more number of cases should be done in this region for validating previous results and for getting a baseline hematological profile for guiding the clinicians in management of these patients.

Conclusion
This study showed lower values of total hemoglobin, RBC count and hematocrit. Age wise increase in hemoglobin and hematocrit was noted till fifth decade. Observations in other studies with MCV values deviating from normal range call for extra attention towards proper nutrition and supplementation of folate, and iron if required. Higher values of RDW and Reticulocyte count were seen; whereas values of RBC indices, Platelet count, TLC and Gran% were in the normal range. These findings are almost same as that of other similar works of Central India. A larger scale work is recommended in this region for a baseline hematological profile for guiding the clinicians in management of these patients.