G6PD Gene Variants Hemolytic Anemia and Gallstone Formation on Ultrasound after Oxidative Drug Exposure

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic disorder that predisposes individuals to oxidative stress-related hemolysis. Exposure to oxidant drugs may trigger acute hemolytic anemia, and recurrent hemolysis may contribute to pigment gallstone formation. This study evaluated the association of G6PD gene variants with hemolytic anemia and gallstone formation after oxidative drug exposure.

Material and Methods: This case-control study included 150 participants, comprising 75 cases and 75 controls, recruited from a Tertiary Care Hospital of Karachi. Cases were patients with confirmed G6PD deficiency who developed acute hemolytic anemia after exposure to oxidative drugs, whereas controls were G6PD-deficient individuals without documented hemolysis or gallstones. Data were collected using a structured proforma and included demographic characteristics, drug exposure history, clinical features, hematologic parameters, and abdominal ultrasonography findings. G6PD deficiency was confirmed by enzyme assay and, where available, molecular analysis. Statistical analysis was performed using standard comparative tests, and odds ratios were calculated to measure associations.

Results: The mean age was similar in both groups, and males comprised about 70% of the study population. Confirmed G6PD gene variants were found in 61 cases (81.3%) compared with 28 controls (37.3%). Oxidative drug exposure was documented in 59 cases (78.7%), which was significantly higher than in controls. Cases had a lower mean hemoglobin level of 8.9 g/dL compared with 12.8 g/dL in controls. Reticulocyte count, indirect bilirubin, and LDH were also markedly raised among cases, with values of 5.8%, 2.8 mg/dL, and 612 U/L, respectively. Clinical features such as pallor (88.0%), jaundice (77.3%), and dark urine (54.7%) were more frequent in cases than in controls. On ultrasonography, gallstones were detected in 21 cases (28.0%) versus 6 controls (8.0%). Gallbladder sludge was present in 9 cases (12.0%). These findings suggest that recurrent hemolysis and oxidative stress may contribute to gallstone formation in patients with G6PD deficiency.

Conclusion: G6PD gene variants were significantly associated with oxidative drug-induced hemolytic anemia and gallstone formation. The findings highlight the importance of early recognition of G6PD deficiency, cautious use of oxidant drugs, and clinical monitoring for biliary complications in affected individuals.

Keywords: G6PD, Gene Variants, Hemolytic Anemia, Gallstone, Oxidative Drug Exposure