Molecular Characterization of a β-Thalassemia Intermedia Patient Presenting Inferior Vena Cava Thrombosis: Interaction of the β-Globin Erythroid Krüppel-Like Factor Binding Site Mutation with Hb E and α⁺-Thalassemia

Abstract

The molecular basis and hematological phenotype of adult Thai β-thalassemia intermedia (β-TI) patients encountered with inferior vena cava (IVC) thrombosis were investigated. Hematological and molecular analysis revealed a trait previously not described. The disease was caused by interaction of the β(+)-thalassemia (β(+)-thal) gene with the -90 (C > T) (HBB: c.-140C > T) transition within the erythroid Krüppel-like factor (EKLF) binding site of the β-globin gene promoter with Hb E (HBB: c.79G > A) and α(+)-thalassemia (α(+)-thal). Hematological data of the patient were compared with those of heterozygous forms of these defects found in his family members and different genotype-phenotype interactions are illustrated. Globin gene haplotype analysis indicates an independent origin of this Thai β(+)-thal gene. Accurate diagnoses as well as knowledge of genotype-phenotype relationships were required for providing appropriate management of such cases.

A large cohort of β+-thalassemia in Thailand: Molecular, hematological and diagnostic considerations

“…However, it has been noted that although having transfusion independence and higher life expectancy, β-TI patients may still suffer from many complications including a hypercoagulable state, pulmonary hypertension and subsequent thrombotic events [14]. We have recently encountered such case of β-TI with these complications [15] . Therefore, accurate diagnosis of thalassemia intermedia is essential to reduce morbidity of the patients.…”

Review article inferior vena cava thrombosis: a case series of patients observed in Taiwan and literature review

“…Abnormalities in pathologic red blood cells, activated platelets, endothelial damage, and splenectomy are established mechanisms of thalassemia that could contribute to VTE [ 66 ]. Although the association between thalassemia and IVCT has been reported sporadically [ 67 ], our findings suggest that the underlying hypercoagulable state of thalassemia may contribute to the development of IVCT, as well as other reported clinical thrombotic events.…”

Elevations of Thrombotic Biomarkers in Hemoglobin H Disease

“…It has been shown that the prevalence of venous thrombotic events in non-transfusion-dependent thalassemia (TDT) or thalassemia intermedia (29%) is higher than that of TDT or thalassemia major (2%) [17]. We have also documented a Thai β-thalassemia intermedia patient with inferior vena cava thrombosis [18]. A recent epidemiological study on the major complications in TDT and non-TDT of adolescent and adult patients in the region has confirmed this [19].…”