Thalassemia

Learning objectives

Thalassemia is an inherited group of hematological disorders
Synthesis of alpha or beta globin chains is deficient, characterized by decreased hemoglobin production
More frequently found in the Mediterranean, Central Africa, China, and South East Asian regions
The majority of hemoglobin is HbA in normal adults, which has two α and two β chains, i.e. α2β2

α thalassemia

α0 thalassemia results from the elimination of α1 and α2 genes and/or regulatory sequences
α+ thalassemia minor results from a single gene deletion or point mutation that prevents normal α chain production
- The resulting anemia is mild and of little anesthetic significance
Hemoglobin H disease is caused by the interaction of α0 and α+ determinants (loss of three genes)
- The clinical picture is of chronic hemolytic anemia with Hb levels of 8–10 g dL
- Stimulates erythropoietin production and results in excess production of large amounts of β-chains
α thalassemia major” occurs when all four alpha globin genes are non-functioning
- Is almost uniformly fatal in utero without intervention

β thalassemia

Is an autosomal recessive defect of the beta-globin chains of the hemoglobin A molecule
The clinical presentation typically manifests at approximately 4 to 6 months of age
A defect in one beta globin allele will result in beta thalassemia minor
- An effective carrier state as individuals are usually asymptomatic or present with anemia
- Hemoglobin levels 2-3 g/dL < normal for age
A defect in both alleles results in beta thalassemia major (Cooley anemia)
- Results in profound anemia requiring lifelong blood transfusions

Intravascular hemolysis:	Perioperative anemia Jaundice, gallstones Splenic sequestration causes anemia and other hematological effects Free iron causes a vascular endothelial inflammatory response and its consequences, e.g. leading to systemic and Pulmonary hypertension (PH), cerebral ischemia, platelet activation, hypercoagulability
Extramedullary erythropoiesis:	Frontoparietal bossing, prominent maxilla and zygomatic arch, compression of neural structures in bony canal including the spinal cord, bony deformities e.g. thoracic cage, spinal column
Systemic effects of anemia:	High output cardiac failure, decreased oxygen delivery leading to poor growth
Multiple transfusions:	Hypervolemia, coagulation defects, immunosuppression, iron overload
Iron overload:	Cardiomyopathy, cardiac hypertrophy, myocarditis, pericarditis Liver failure and cirrhosis Renal tubular dysfunction, loss of concentrating renal function, and increased excretion of calcium, magnesium, and phosphate Endocrionpathy (diabetes, hypothyroidism, hypoparathyroidism, adrenal insufficiency) Immunosuppression: increased risk of infection

Complete blood count
Hemoglobin electrophoresis
DNA-testing
Metzer index, not a definitive test but in can suggest the possibility of thalassemia