β-Thalassemia Intermedia: A Bird’s-Eye View

Abstract

Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison to the more severe β-thalassemia major.

Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy

“…It has been shown that chronic hemolysis leads to NO depletion due to NO scavenging, arginine catabolism, and endogenous NO synthesis inhibition, as well as to enhanced platelet activation and increased endothelin-1 release. All of those events in turn lead to a vasculopathy characterized by endothelial dysfunction, increased vascular tone, inflammation, hypercoagulability, and, finally, vascular remodeling and destruction of the pulmonary vasculature, which ultimately results in hemolytic anemia-associated pulmonary hypertension [40][41][42].…”

Acute Hepatitis-A Infection Induced Anemia in Concurrence of Glucose-6-Phosphate Dehydrogenase Deficiency and Thalassemia Trait: A Case Report

“…Patients with thalassemia intermedia with a more severe clinical picture are usually diagnosed between the ages of 2-6 years and continue their life without requiring transfusions or transfusions are rarely required. However, growth and developmental delay can be present 17,18 . In my case, thalassemia intermedia was considered, because patient was 3 years old, suff ered from developmental delay, and required transfusion.…”

“…About 1.5% of the world's population (80-90 million people) is estimated to carry the beta thalassemia trait. Th e prevalence of beta thalassemia is high in Mediterranean countries, the Middle East, Asia, Southeast China, and Far East countries as well as the North African coast and South America 17,18 . Th e frequency of beta thalassemia in Turkey was found 2.1% 16 .…”

Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia

“…34,35 Hemolytic anemia-associated pulmonary hypertension results from endothelial dysfunction, increased vascular tone, inflammation, hypercoagulability, vascular remodeling, and destruction of the pulmonary vasculature. 1,36,37 All these factors lead to elevated sFLT-1 levels among TI patients with pulmonary hypertension and those with splenectomy. Receiver operating characteristic curve analysis also showed that the cutoff value of sFLT-1 at 110 pg/mL could differentiate patients with and without pulmonary hypertension with high sensitivity and specificity.…”

“…Three main factors are responsible for the clinical sequelae of TI: ineffective erythropoiesis, chronic anemia, and iron overload. 1 Transfusional iron overload can affect heart function by directly damaging tissue through iron deposition or via ironmediated effects at other sites. The main cardiac abnormalities reported in patients with thalassemia and iron overload are left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathies, arrhythmias, and pericarditis.…”