Thalassaemia Intermedia: an Update

Abstract

Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI) has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan.

Genetic modifiers of -thalassemia and clinical severity as assessed by age at first transfusion

“…Approximately 5-10% of patients live without requiring periodic blood transfusions and are said to have thalassemia intermedia. 3 These two forms of the disease are the extreme ends of a broad range of clinical variability: patients might need to start transfusions after days, months or even years of life, demonstration of a great variation in disease severity.…”

“…11 Thalassemia intermedia patients were defined as patients who had never been transfused, or had only been transfused sporadically during infections or surgery (<10 blood units in total). 3 The β-thalassemia mutations were of HBB:c118C>T/HBB:c118C>T type in 92.4% of cases and HBB:c118C>T/HBB:c.20delA type in 6.3% of the studied sample; the remaining mutations are reported in Table 1. The continuous distribution of the phenotypic severity among thalassemia patients was measured by the time at which they started transfusion therapy.…”

“…This hypothesis seems to be supported by our results, as all variables and the hierarchy of their effects agree with previous studies on genetic modifiers of both Hb F levels and the clinical severity of β-thalassemia, even though other unknown genetic factors and clinical conditions might be co-responsible for the need for transfusions. 3,11,15,23,24 To the best of our knowledge, the present study is the first to analyze the severity of β-thalassemia in a quantitatively defined manner and to include such a complete set of known predictors. In a previous study, Galanello et al 11 studied the effect of two SNP (rs11886868 in BCL11A and rs9389268 in the HBS1L-MYB intergenic region) and a-globin gene defects on the phenotypic expression (defined as major versus intermedia status) of Sardinian patients with β 0 -thalassemia.…”

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

“…Four (5.5 %) patients had evidence of EMH including one with an intradural mass in the D 12 region presenting with features of spinal cord compression and another patient had a mass in the urinary bladder presenting with frank hematuria. 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.…”

Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study

“…1,2 It is now established that such clinical phenotypes lie in severity between those of thalassemia minor (clinically silent, mildly hypochromic, and microcytic anemia) and transfusion-dependent thalassemia major (TM), although there is substantial clinical overlap between the 3 conditions. 3 Three main factors are responsible for the clinical sequelae of TI: ineffective erythropoiesis, chronic anemia, and iron overload. 3 The degree of ineffective erythropoiesis is the primary determinant of the development of anemia, whereas peripheral hemolysis of mature red blood cells (RBCs) remains secondary.…”