Coinheritance Of Glucose-6-Phosphate Dehydrogenase Deficiency In Sickle Cell Anemia Patients: Impact On Clinical, Biochemical And Hematological Parameters

Abstract

Background: Sickle cell disease (SCD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency are among the most common hereditary hemolytic disorders globally, often co-existing in populations where malaria was historically endemic. The co-inheritance remains controversial, with limited data from regions with high prevalence such as the Eastern Province of Saudi Arabia. This study aimed to evaluate the clinical, hematological, and biochemical differences between patients with SCD alone and those with co-inherited G6PD deficiency (SCD/G6PDD), with a focus on fetal hemoglobin (Hb F), hemolysis markers, and disease severity indicators.

Methods: A cross-sectional analytical study was conducted at the Center of Genetic Blood Diseases, Al-Ahsa, Saudi Arabia, including 169 confirmed SCD patients—98 with SCD only and 71 with SCD/G6PDD. Clinical data were collected via validated questionnaires and chart reviews. Hematological and biochemical analyses included complete blood count, hemoglobin electrophoresis, liver enzymes, and bilirubin levels. Statistical analysis was performed using SPSS version 28, with significance set at p<0.05.

Results: No significant differences were observed between the two groups regarding vaso-occlusive crisis frequency, hospitalizations, or hydroxyurea usage. Hematological indices such as hemoglobin, hematocrit, MCV, and platelet counts were comparable. However, the SCD/G6PDD group exhibited significantly higher total bilirubin levels (p=0.013) and Hb F levels (mean 37.32% vs. 27.06%, p=0.018), while hemoglobin S was significantly lower (p=0.008). Liver enzymes and minor hemoglobin (HbA1, HbA2) showed no significant variation.

Conclusion: Co-inheritance of G6PD deficiency in SCD patients does not substantially alter clinical severity but is associated with increased Hb F and bilirubin, possibly indicating a protective hematologic effect. These findings highlight the need for genotype-based management strategies and underscore the importance of further genomic and longitudinal studies in similar populations.