Genotypic and hematologic association of pulmonary hypertension in non-transfusion-dependent thalassemia
Year: 2025
Type: article
Study design: Observational Study
Abstract: Objectives Thalassemia intermedia phenotype, older age, splenectomy, hypercoagulability, chronic hemolysis, hypoxia, nitric oxide depletion, endothelial perturbation, and iron overload contribute to pulmonary hypertension in thalassemia. We aimed to explore the association of genotype and disease parameters on pulmonary hypertension in non-transfusion-dependent thalassemia (NTDT). Material and Methods Prospective cross-sectional data comprising demographics, disease characteristics, genotype, and pulmonary hypertension on 50 non-transfusion-dependent hemoglobin (Hb) E beta-thalassemia patients were collected. Results The majority (n = 32,64%) required either one or no transfusion and had median Hb of 8.5 g/dL (range 5.9–14.1) and median fetal hemoglobin (Hb F) of 36.8% (range 2.5–76.8%). A mild Mahidol score was seen in 42 (84%) cases. Pulmonary hypertension was detected in 32%, grade I disease in 28%, and none were symptomatic. High Hb F was noted where compound heterozygosity for intervening sequence (IVS)1-5(G>C)+codon(CD)26(G>A) beta-globin mutation and alpha(-α)3.7 and -α4.2 deletion were detected. Mean pulmonary artery pressure (MPAP) was high when Hb F >25% but was not significant (P = 0.67). The odds ratio for pulmonary hypertension at serum ferritin more than 500 ng/ml was 9.4 (confidence interval 2.58-33.27, P = 0.00038). Older patients had high ferritin (P = 0.0025). Around 25% variability in MPAP was influenced by age, number of transfusions, ferritin, Hb F, and Hb. None underwent splenectomy or had prior thromboembolism or heart failure. Conclusion In spite of young age, mild Mahidol score, and high Hb F in those with alpha deletion and beta mutation, pulmonary hypertension was still a significant complication even in the absence of splenectomy or prior thromboembolic episode in non-transfusion-dependent thalassemia. As this was the foremost study investigating the relationship of genotypes with complications in NTDT in India, future multicenter studies are paramount.
Authors: M. Vinodhini, Rajib De, Prakas Kumar Mandal, Shyamali Dutta
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4410178520