European Journal of Cardiovascular Medicine

Sickle cell disease (SCD) represents one of the most prevalent inherited hemoglobinopathies worldwide, characterized by chronic hemolysis, recurrent vaso-occlusive episodes, and systemic organ dysfunction. It is caused by a point mutation in the β-globin gene that results in the substitution of valine for glutamic acid at the sixth position, leading to the formation of sickle-shaped erythrocytes with compromised oxygen-carrying capacity and shortened lifespan [1].

SCD is highly prevalent in regions such as sub-Saharan Africa, the Middle East, Mediterranean countries, and the Indian subcontinent, where it poses a significant public health burden [2]. India is among the top three countries contributing to nearly half of the global SCD burden, with a prevalence ranging from 1% to 44% depending on geographic and ethnic variation [3]. In Odisha, certain tribal and non-tribal populations exhibit particularly high prevalence rates, influenced by endogamy and regional genetic patterns [4].

The clinical course of SCD is highly heterogeneous and may involve acute complications like vaso-occlusive crisis (VOC), haemolytic crisis, sequestration crisis, aplastic anemia, and life-threatening events such as acute chest syndrome and stroke [5]. Chronic manifestations such as cholelithiasis and organomegaly may also develop due to cumulative hemolytic damage.

The pathophysiology of SCD is multifactorial and includes oxidative stress, endothelial dysfunction, and chronic inflammation. Among these, derangements in lipid metabolism have received increasing attention for their potential role in modulating disease severity [6]. Hypocholesterolemia and hypertriglyceridemia have been frequently observed in SCD patients, possibly due to increased erythropoiesis, hemolysis-induced cholesterol consumption, and plasma dilution [7]. Furthermore, decreased levels of HDL-C and apolipoprotein A1 (apoA1), along with impaired nitric oxide (NO) bioavailability, have been linked to vascular dysfunction in both SCD and atherosclerotic conditions [8].

Studies suggest that dyslipidemia in SCD may not merely be a biochemical abnormality but also a reflection of underlying disease activity and severity. Elevated triglycerides and reduced HDL-C have been associated with endothelial injury, increased frequency of VOC, and inflammatory states, highlighting their potential utility as biomarkers of clinical risk stratification [9].

Despite growing global interest, data on the lipid profiles and their clinical correlations in Indian patients with SCD remain limited. In this context, the present study was designed to investigate the clinicodemographic profile of adult SCD patients in Eastern India, with a particular focus on the clinical manifestations such as VOC and haemolytic crises.

Study Design and Setting: This hospital-based, observational cross-sectional study was conducted in the Department of General Medicine at PGIMER and Capital Hospital, Bhubaneswar. The study duration spanned from May 2023 to December 2024 and involved adult patients diagnosed with sickle cell disease (SCD), either during outpatient visits or inpatient admissions.

Study Population: A total of 157 adult individuals with confirmed sickle cell disease were enrolled consecutively. Both previously diagnosed and newly confirmed cases were included. Informed written consent was obtained from all participants following approval from the Institutional Ethics Committee.

Inclusion Criteria:

• Adults aged ≥18 years with a confirmed diagnosis of SCD by high-performance liquid chromatography (HPLC).
• Patients in either steady state or presenting with clinical manifestations of SCD.

Exclusion Criteria:

• Patients on lipid-lowering medications (e.g., statins) for any indication.
• Individuals with known familial hypercholesterolemia or dyslipidemia.
• Pregnant women.
• Patients living with HIV on antiretroviral therapy.

Sample Size Calculation: Using the Raosoft sample size calculator with a 5% margin of error and 95% confidence level, and based on a previously reported prevalence of 9.43% for SCD in the region, the minimum required sample size was estimated at 130. However, 157 patients were included to enhance statistical robustness.

Data Collection Tools and Techniques: Data were collected using structured case record forms, direct patient interviews, physical examinations, and review of bed-head tickets and laboratory reports. Demographic, clinical, and laboratory data were collected using a structured case record proforma. Patient interviews, physical examinations, and review of clinical records formed the basis of data collection. The geographical distribution of patients was documented to explore regional disease burden. The clinical presentation was recorded in terms of specific sickle cell-related complications such as vaso-occlusive crisis (VOC), haemolytic crisis, cholelithiasis, sequestration crisis, acute chest syndrome, cerebrovascular accident (CVA), and aplastic crisis. Treatment history—including hydroxyurea (HU) therapy and history of blood transfusions—was also noted. Splenomegaly status was documented based on clinical and/or radiological assessment.

Statistical Analysis: Data were recorded in Microsoft Excel and analyzed using SPSS version 26.0. Categorical variables were expressed as frequencies and percentages, while continuous variables were summarized as means with standard deviations or medians with interquartile ranges depending on data distribution. Group comparisons were made using Mann–Whitney U test for non-parametric data. Logistic regression models were employed to assess associations between lipid parameters and crisis presentations, adjusting for age, sex, hydroxyurea use, and transfusion history. A p-value of <0.05 was considered statistically significant.

A total of 157 adult patients with confirmed sickle cell disease (SCD) were enrolled in the study. The age distribution of participants indicated that the majority belonged to the 21–30-year age group, followed by the 15–20-year and >30-year groups, respectively, demonstrating a higher burden of disease among younger adults (Table 1). Female participants slightly outnumbered males, reflecting a near-equal gender distribution within the study population (Table 2).

Table 1: Age Group of Sickle Cell Cases (n=157)

Table 2: Gender distribution of Sickle Cell Cases (n=157)

Geographical analysis revealed that most patients presented from Nayagarh, Angul, and Khordha districts, which are in close proximity to the tertiary care center. Collectively, these three districts accounted for over half of the total sample. Other notable contributors included Koraput and Kalahandi, while the remaining districts had fewer representations (Table 3). A visual depiction of case concentration across districts further illustrated this regional clustering (Figure 1).

 Table 3: Geographical Representation of Cases (n=157)

Figure 1: Visual representation of concentration of cases in different districts of Odisha presenting to our centre

The clinical manifestations observed among the participants were diverse, with vaso-occlusive crisis (VOC) being the most common, followed by haemolytic crisis. Chronic complications such as cholelithiasis were less frequent, while severe acute complications including acute chest syndrome, sequestration crisis, cerebrovascular accident (CVA), and aplastic crisis were rare (Table 4).

Table 4: Profile of Clinical presentation in enrolled patients (n=157)

Further subgroup analysis among 129 patients, comparing those with VOC to those in steady-state, revealed significant associations with several demographic and clinical variables (Table 5). Patients experiencing VOC were significantly younger compared to those in the steady-state group (p < 0.001). No statistically significant difference in sex distribution or hydroxyurea therapy status was observed between the groups. However, splenomegaly was more prevalent among VOC patients, and a history of blood transfusion showed a strong association with VOC occurrence (p < 0.001 for both), suggesting these factors may serve as clinical indicators of disease severity.

Table 5: Association of demographic and clinical characteristics with Vaso-occlusive crisis (n=129)

This study evaluated the clinicodemographic characteristics and pattern of clinical manifestations among adult sickle cell disease (SCD) patients attending a tertiary care center in Eastern India. The findings highlight important trends in age distribution, gender, geographical clustering, and clinical profiles, especially focusing on the most common complication—vaso-occlusive crisis (VOC).

The age-wise analysis revealed that nearly half of the participants were in the 21–30-year age group, followed by 15–20 years and >30 years (Table 1). This aligns with prior research indicating that young adulthood is the most vulnerable period for clinical complications in SCD due to cumulative organ damage and increased exposure to physical and psychosocial stressors [10]. Kidwell et al. reported a similar trend, with the majority of high-utilizer patients averaging 28.8 years of age [10].

In terms of gender, the distribution was nearly equal, with a slight female predominance (Table 2). This contrasts with studies suggesting higher healthcare utilization among males [10]; however, it may reflect regional differences in health-seeking behavior or access to care.

Geographical analysis showed that the majority of cases were concentrated in Nayagarh, Angul, and Khordha districts (Table 3), likely due to both regional prevalence and geographic proximity to the treatment facility. Previous studies from Odisha have reported heterogeneous distribution of the sickle gene, with higher burden among certain tribal and non-tribal populations [11]. The clustering observed here supports findings from community-based screening initiatives that emphasized the need for region-specific disease monitoring and intervention strategies [11].

VOC emerged as the most prevalent clinical complication, affecting 61.8% of patients (Table 4), consistent with global and regional reports indicating VOC as the hallmark of SCD morbidity [12]. Hemolytic crisis was the second most common manifestation, occurring in 25.5% of patients. Other complications such as cholelithiasis, acute chest syndrome, sequestration crisis, and cerebrovascular accidents were observed infrequently, consistent with prior Indian studies highlighting the clinical heterogeneity of SCD [13].

To further explore the burden of VOC, we analyzed demographic and clinical correlates among patients in crisis versus steady state (Table 5). Patients with VOC were significantly younger than those in steady state, underscoring earlier onset and possibly more aggressive disease progression in this age group (p < 0.001). Similar findings were reported by Ossama Zakaria et al. and Nirmish Shah et al., where younger patients demonstrated higher VOC frequency and hospitalization rates [14,15].

Splenomegaly was significantly associated with VOC (p = 0.001), which reflects regional differences in SCD pathophysiology. In contrast to autosplenectomy seen in Western populations, Indian SCD patients often retain splenic function into adulthood [16]. This may be attributed to higher fetal hemoglobin levels, as shown by Lakhani et al., who noted persistent splenomegaly in over 77% of Indian SCD adults [16].

Furthermore, history of blood transfusions was strongly associated with VOC (p < 0.001), possibly indicating a more severe or recurrent disease phenotype. The requirement for transfusions in VOC could also reflect associated complications such as acute anemia or organ dysfunction, corroborated by prior Indian studies on transfusion burden in SCD [17].

Interestingly, hydroxyurea (HU) therapy did not show a statistically significant difference between the crisis and steady-state groups (p = 0.564). Although HU is known to reduce VOC frequency and improve hematologic parameters, variable compliance, inconsistent dosing, or delay in therapy initiation may affect real-world outcomes [18].

This study highlights a substantial burden of VOC among young adults with SCD in Eastern India. Age, splenomegaly, and transfusion history were significantly associated with VOC episodes, underscoring the importance of early risk stratification and regular follow-up. The geographic and demographic patterns identified here can inform public health policies for targeted screening and intervention.

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