Thalassemia

Over 60,000 children are born annually with severe beta-thalassemia.

Global regions that are primarily affected include the Mediterranean, North Africa, and Southeast Asia, where alpha thalassemia is more common.

Beta-trait carrier status has a global prevalence of approximately 1.5%.

Over 200,000 pts are currently receiving treatment for thalassemias.

In endemic areas with highest frequency, carrier status is present in as many as 1:7 individuals, and thalassemia major can occur in 1:158 live births.

Abnormal globin chains result in severe anemia (mild microcytic anemia in those with carrier status).

CHF is the leading cause of death.

End-organ effects of hemochromatosis from chronic iron therapy: Cardiomyopathy, cirrhosis, endocrinopathies (e.g., diabetes, hypopituitarism).

Diabetes mellitus is common.

Restrictive lung dysfunction and pulm Htn.

Airway difficulties, including maxillofacial abnormality secondary to bone marrow expansion.

Hypercoagulopathy in asplenic pts, and coagulopathy in pts with cirrhosis.

Alloimmunization secondary to multiple blood transfusions. Obtaining appropriately cross-matched blood may require prolonged testing.

Difficult airway secondary to maxillary deformation in up to 19%

Cardiac arrhythmias or HF

Hypercoagulability

Pulm Htn

Immunocompromisation

Thalassemia is a heterogeneous group of inherited microcytic anemias that result from a genetic mutation causing a defect in the synthesis of one or more globin chain subunits of the HbA, which is normally composed of α2β2.

Thalassemia is classified according to the genotype that correlates with clinical severity.

Alpha thalassemia: Alpha globin gene deletion leads to a decrease in alpha chain production with a relative overproduction of beta chains. This leads to formation of β4 tetramers, which causes RBCs to be more rapidly removed leading to anemia.

Alpha thalassemia silent carrier: One gene absent (aa/a-); healthy except occasional mild anemia.

Alpha thalassemia trait: Two genes absent on the same or different chromosomes (a-/a- or aa/--); mild anemia.

Alpha thalassemia intermedia (Hb H disease): inactivation of three genes (a-/--) leads to a spectrum for manifestations; mild to moderately severe anemia, splenomegaly, icterus, abnormal RBC indices; recurrent infections. Heinz bodies = beta chain tetramers. Hb H disease results in poor oxygen delivery to the tissues due its high affinity for oxygen.

Alpha thalassemia major (Hb Barts): Complete deletion of all alpha chain genes resulting in the formation of Hb-Bart’s, which has an exceptional affinity for oxygen resulting in extremely limited tissue oxygen delivery. Incompatible with life; hydrops fetalis unless intrauterine blood transfusions.

Beta thalassemia: Decreased beta chain production relative to the alpha chain production as a result of mutation resulting in either absence (beta o) or decrease (beta+) in the production of beta globin. Alpha chains are in excess and precipitate leading to inadequate erythroid maturation and hemolysis. In most severe forms, this leads to splenomegaly, anemia, massive expansion of medullary and extramedullary erythropoietic tissue leading to skeletal growth, and metabolic abnormalities.

Beta thalassemia is a silent carrier (beta/beta+); it shows no clinical symptoms except for low RBC counts.

Beta thalassemia trait (beta/beta+) = beta thalassemia minor: Mild anemia, abn RBC indices, hypochromia, microcytosis.

Beta thalassemia intermedia (beta/beta o, beta+/beta+, beta+/beta o): A compound heterozygous state; profound anemia, which periodically may require transfusion support and occasionally splenectomy.

Beta thalassemia major (beta o/beta o) = Cooley’s anemia, transfusion-dependent anemia, massive splenomegaly, bone deformities, growth retardation, and abnormal facies. As a result of chronic anemia and ineffective erythropoiesis, bone expansion and extramedullary erythropoiesis may develop in liver and spleen, and marrow space expansion at sites such as the cranium and paravertebral areas can lead to disfiguring bony changes. Deaths are usually secondary to cardiac manifestations, including cardiomyopathies and heart failure. The incidence of pulm Htn and lung fibrosis increase, leading to a restrictive pattern of lung dysfunction.