Studies in haemoglobin E beta‐thalassaemia

Abstract

SummaryHaemoglobin E b-thalassaemia is the commonest form of severe thalassaemia in many Asian countries, but little is known about its natural history, the reasons for its clinical diversity, or its optimal management. Despite its frequency, haemoglobin E b-thalassaemia is often managed in an illdefined and haphazard way, usually by demand transfusion. We studied a cohort of Sri Lankan patients with haemoglobin E b-thalassaemia over 5 years, and identified several genetic and environmental factors possibly contributing to the phenotypic diversity of the disorder. These included modifiers of haemoglobin F production, malaria and age-related changes in adaptation to anaemia. Our findings suggest that in many patients, haemoglobin E b-thalassaemia can be managed without transfusion, even with low haemoglobin levels. Agerelated changes in the pattern of adaptation to anaemia suggest that more cost-effective approaches to management should be explored.

Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait

“…31,32 As shown in our data and previous studies, 4,22 the phenotypic heterogeneity occurs within a narrow range of hemoglobin levels, with the pretransfusion hemoglobin of the severe group being only slightly lower than the steady-state hemoglobin levels in the moderate groups. 4 For economic and related reasons, including compliance, it has not been possible to maintain the pretransfusion Hb levels above the 9 g/dL range, as is more usual practice in severe Figure 1.…”

“…Mean Hb levels in moderate patients (6.35 g/dL) did not differ significantly from the pretransfusion levels in the severe group (5.79 g/dL; P 5 .140), as observed previously. 4,22 Likewise, HbF% did not differ between the 2 groups. Compared with patients with moderate phenotypes, patients with severe phenotypes had significantly greater iron loading and higher ALT but did not show evidence of increased erythroid drive or erythropoiesis (EPO, sTfR, and GDF15).…”

“…Long-term follow-up of this cohort has enabled classification of patients into moderate and severe clinical phenotypes, as previously detailed. 4,22 Briefly, the moderate group included patients who either had grown and developed normally without regular transfusions (apart from episodic transfusions during infection or pregnancy), or had been started on transfusions elsewhere for uncertain reasons and in whom transfusion had been safely stopped. The severe group comprised patients who had increasing splenomegaly, retarded growth, bone deformity, or poor exercise tolerance, necessitating treatment with regular transfusion; for economic and related reasons, transfusions were dosed to control these complications, rather than achieve a particular pretransfusion hemoglobin level.…”

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

“…Ineffective red cell production by the bone marrow (ineffective erythropoiesis) forces expansion of the hematopoietic tissue outside the marrow medulla and leads to hematopoietic compensatory involvement, mostly in the form of masses, of other regions in the body-the phenomenon termed extramedullary hematopoiesis [18]. Olivieri et al [19] in a review of 109 patients with Ebthalassemia, reported only one patient had a fracture occurred without significant trauma and severe facial deformity was observed in only two patients. Eleven (15.28 %) patients had developed VTE.…”

“…This probably negated the need for a routine antibacterial and anti-malarial prophylaxis. Olivieri et al [19] in a review of 109 patients with Eb-thalassemia, reported only one splenectomized patient with severe lifethreatening infections. The predisposing factors of infections in thalassemia include splenectomy, iron overload, anemia, and granulocyte dysfunctions [22].…”