hematology and oncology
Thalassemias
Symptoms and Signs of Thalassemias
Clinical features of thalassemias are similar but vary in severity depending on the amount of normal hemoglobin present. Patients with a single alpha + allele (alpha/alpha;alpha/--) are clinically normal and are called silent carriers. Patients who are heterozygous with defects in 2 of the 4 genes such as two alpha + alleles (alpha/--;alpha/--) or one alpha 0 allele (alpha/alpha;--/--) tend to develop mild to moderate microcytic anemia but no symptoms. These patients have alpha-thalassemia trait. Defects in 3 of the 4 genes caused by coinheritance of both alpha + and alpha 0 (alpha/--;--/--) severely impair alpha-chain production. Impaired alpha-chain production results in the formation of tetramers of excess beta-chains termed Hb H or, in infancy, gamma-chains termed Bart’s hemoglobin. Patients with Hb H disease often have symptomatic hemolytic anemia and splenomegaly. Defects in all 4 genes via two alpha 0 alleles (--/--;--/--) is a lethal condition in utero (hydrops fetalis), because hemoglobin that lacks alpha chains cannot transport oxygen. In beta-thalassemia, clinical phenotypes are classified into 3 groups based on the degree to which beta globin production is impaired: Minor (or trait) Intermedia Major Beta-thalassemia minor (trait) occurs in patients who are heterozygous (beta/beta + or beta/beta 0), who are usually asymptomatic with mild to moderate microcytic anemia. This phenotype may also occur in mild cases of beta +/beta +. Beta-thalassemia intermedia is a variable clinical picture that is intermediate between thalassemia major or minor, caused by inheritance of 2 beta thalassemia alleles (beta +/beta 0 or severe cases of beta +/beta +). Beta-thalassemia major (or Cooley anemia) occurs in patients who are homozygous (beta 0/beta 0) or severe compound heterozygotes (beta 0/beta +) and results from severe beta globin deficiency. These patients develop severe anemia and bone marrow hyperactivity. Beta-thalassemia major manifests by age 1 to 2 years with symptoms of severe anemia and transfusional and absorptive iron overload. Patients are jaundiced, and leg ulcers and cholelithiasis occur (as in Sickle Cell Disease ). Splenomegaly, often massive, is common. Splenic sequestration may develop, accelerating destruction of transfused normal red blood cells. Bone marrow hyperactivity causes thickening of the cranial bones and malar eminences. Long bone involvement predisposes to pathologic fractures and impairs growth, possibly delaying or preventing puberty. With Overview of Iron Overload , iron deposits in heart muscle may cause heart failure. Hepatic siderosis is typical, leading to functional impairment and cirrhosis. Iron chelation is usually necessary. 