Sickle cell disease remains a major public health concern, particularly in regions like western Odisha. It is characterized by the production of abnormal hemoglobin (HbS) resulting from a single amino acid substitution. Experimental and clinical evidence demonstrates that hyperhomocysteinemia contributes to atherogenesis and vaso-occlusion through endothelial injury, platelet activation, and thrombus formation. Elevated plasma homocysteine is an established risk factor for ischemia and vascular events. Furthermore, nutritional deficiencies in cofactors such as vitamin B12 and folic acid frequently exacerbate homocysteine elevation. Given the high baseline risk of ischemic complications in SCD, this study investigates the clinical implications of serum homocysteine levels among patients presenting to our institution

Study Design: Cross-sectional analytical study. Setting: Department of Biochemistry, Department of General Medicine, and the Sickle Cell Institute at VIMSAR, Burla. Duration November 2018 to October 2020. Study Population n-patients and out-patients diagnosed with SCD via sickling test and HPLC screening. Sample Size Calculated using standard deviation parameters from prior literature (σ=6.9, absolute error d=0.05, Z=1.96), yielding a minimum requirement of 73 patients, fixed at a total study cohort of 73 cases matched with controls. Inclusion & Exclusion Criteria Cases and controls were matched by age and gender. Patients with confounding conditions known to elevate homocysteine—such as diabetes mellitus, hypertension, ischemic heart disease, renal or hepatic failure, pre-eclampsia, malignancies, or a history of smoking—were excluded. Collection & Analysis 5 ml of fasting blood was collected, centrifuged at 3000 rpm for 10 minutes, and serum homocysteine was estimated using ELISA. Data analysis was performed using SPSS software, applying independent sample t-tests for continuous variables and Chi-square tests for discrete variables.

Description: Breakdown of the study population based on biological sex. Statistical Significance: Demonstrates demographic proportions within the cohort. Table 1: Sex-Wise Distribution of Patients with SCD Gender Percentage (%) Male 69% Female 31% Description: Regional representation of patients reporting to the institute across districts in Odisha. Statistical Significance: Reflects regional disease burden mapping to local clinics. Table 2: Geographical Distribution of SCD Patients District Percentage (%) Sambalpur 29% Bargarh 29% Jharsuguda 10% Bolangir 7% Sundergarh 6% Sonepur 5% Boudh / Deogarh / Kalahandi 3% each Anugul / Others 2% each Nuapara 1% Description: Frequency of various clinical manifestations observed upon initial patient evaluation. Statistical Significance: Highlights Vaso-occlusive crisis as the predominant presentation. Table 3: Clinical Presentation at Registration (n=100) Clinical Presentation Number of Patients (n) Percentage (%) Vaso-occlusive Crisis (VOC) 66 66% Acute Chest Syndrome 44 44% Anemia 15 15% Jaundice 9 9% Fever 6 6% Description: Statistical evaluation of homocysteine concentrations between the study group and healthy controls. Statistical Significance: Highly significant elevation (p<0.0001) observed in SCD patients. Table 4: Comparison of Serum Homocysteine in SCD Patients vs. Controls Homocysteine Parameter (μmol/L) Patients with SCD Controls Mean ± SD 21.6±7.8 13.2±4.4 Median 21.7 13 Range 7.9 – 42 7.2 – 21 Description: Comparison of mean serum homocysteine levels among SCD patients with and without folic acid supplementation. Statistical Significance: Patients without supplementation showed markedly elevated homocysteine pools. Table 5: Impact of Folic Acid Therapy on Serum Homocysteine Levels Treatment Group Mean Homocysteine Level (μmol/L) With Folic Acid Therapy (5 mg) 17.8 Without Folic Acid Therapy 27.0

The findings of this cross-sectional study confirm that serum homocysteine concentrations are significantly elevated in adult patients suffering from sickle cell disease compared to healthy controls. Regression analysis further revealed a positive association between higher serum homocysteine levels and an increased annual rate of vaso-occlusive crises (r=0.3045,p=0.0021). Elevated homocysteine promotes endothelial damage and a prothrombotic state, aggravating microvascular occlusion in SCD. Furthermore, patients not undergoing folic acid therapy exhibited substantially higher homocysteine levels than those receiving supplementation, emphasizing the role of nutritional management in mitigating vascular risk factors in this population.

Serum homocysteine is notably elevated in subjects with sickle cell disease and serves as an important biochemical correlate for frequent vaso-occlusive crises. Routine screening and targeted nutritional support, such as folic acid therapy, represent vital adjuncts in comprehensive SCD management. Future prospective studies exploring precise nutritional and metabolic interventions are recommended to optimize clinical outcomes.

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