Thalassemia : Definition , Clinical Features & Complications

Thalassemia is a heterogeneous group of blood disorders affecting the hemoglobin genes and resulting in ineffective erythropoiesis. The decreased production of hemoglobin results in anemia in early age and frequent blood transfusions are required to keep up the hemoglobin levels. This activity outlines the evaluation and treatment of thalassemia and highlights the role of an interprofessional team in managing the patients with this condition.

Objectives:

• Summarize the etiology of thalassemias.

• Review of different laboratory and bedside evaluation techniques in the management of thalassemia patients.

• Outline the treatment and management options available for thalassemia.

• Identify interprofessional team strategies for improving care coordination and communication to improve outcomes in thalassemia.

Introduction

Thalassemias are a heterogeneous grouping of genetic disorders that result from a decreased synthesis of alpha or beta chains of hemoglobin (Hb). Hemoglobin serves as the oxygen-carrying component of the red blood cells. It consists of two proteins, an alpha, and a beta. If the body does not manufacture enough of one or the other of these two proteins, the red blood cells do not form correctly and cannot carry sufficient oxygen; this causes anemia that begins in early childhood and lasts throughout life. Thalassemia is an inherited disease, meaning that at least one of the parents must be a carrier for the disease. It is caused by either a genetic mutation or a deletion of certain key gene fragments.

Alpha thalassemia is caused by alpha-globin gene deletion which results in reduced or absent production of alpha-globin chains. Alpha globin gene has 4 alleles and disease severity ranges from mild to severe depending on the number of deletions of the alleles. Four allele deletion is the most severe form in which no alpha globins are produced and the excess gamma chains (present during the fetal period) form tetramers. It is incompatible with life and results in hydrops fetalis. One allele deletion is the mildest form and is mostly clinically silent.

Beta thalassemia results from point mutations in the beta-globin gene. It is divided into three categories based on the zygosity of the beta-gene mutation. A heterozygous mutation (beta-plus thalassemia) results in beta-thalassemia minor in which beta chains are underproduced. It is mild and usually asymptomatic. Beta thalassemia major is caused by a homozygous mutation (beta-zero thalassemia) of the beta-globin gene, resulting in the total absence of beta chains. It manifests clinically as jaundice, growth retardation, hepatosplenomegaly, endocrine abnormalities, and severe anemia requiring life-long blood transfusions. The condition in between these two types is called beta-thalassemia intermedia with mild to moderate clinical symptoms.

• One mutated gene: Mild signs and symptoms. The condition is called thalassemia minor.

• Two mutated genes: Signs and symptoms will be moderate to severe. This condition is called thalassemia major, or Cooley anemia. Babies born with two mutated beta hemoglobin genes are usually healthy at birth but disease starts to manifest after 6 months of life when fetal hemoglobin (Hb-gamma) disappears and is replaced by adult Hb.

The excess unpaired alpha-globin chains in beta-thalassemia aggregate and form precipitates that damage red cell membranes and result in intravascular hemolysis. This premature death of erythroid precursor cells leads to ineffective erythropoiesis and later results in extramedullary expansion of hematopoiesis.

Coinheritance of alpha thalassemia: Beta-thalassemia patients with coinheritance of alpha thalassemia have a milder clinical course due to a less severe alpha-beta chain imbalance.

Coexistence of sickle cell trait: The presence of sickle cell trait with beta-thalassemia is a major hemoglobinopathy and results in manifestations of sickle cell disease. Unlike sickle cell trait in which major Hb is HbA, in the co-existence state the major Hb is HbS which constitutes more than 60% of Hb depending on the nature of the disease (beta-zero or beta-plus0.)

Hemoglobin (HbE) is also a common Hb variant found in Southeast Asia population. It has a correlation with a beta-thalassemia phenotype, as people with thalassemia in this territory are commonly found to have HbE.