Thalassemia Anemia - Hematology

Snapshot
A 22-year-old Vietnamese woman presents for a routine gyn exam. Her menstrual cycle is normal, and there is no evidence of other bleeding. Guaiac is negative. Her hemoglobin is at 11 (12-16), RBC is 5.8 (3.5-5.5), and an MCV of 70 (80-100) with a normal RDW of 10. WBC and platelets are normal. Hemoglobin electrophoresis shows an increase in the amount of Hgb A2, and Hgb F.
Introduction

Autosomal recessive disease caused by decreased production of hemoglobin may involve mutations in α (α-thalassemia) or β (β-thalassemia) globin gene There are 4 α genes (2 on each chromosome) and 2 β genes that make up three forms of Hgb Hgb A subunits: α,α,β,β 96-98% of adult hemoglobin Hgb A2 subunits: α,α,δ,δ present in trace amounts in adults. Hgb F subunits: α,α,γ,γ declines in the first year of life cannot bind 2,3 DPG so has a left-shifted curve α-thalassemia types 1 gene deletion is asymptomatic 2 gene deletion is associated with a mild anemia with RBC hyperplasia called α-thalassemia trait seen in Asians and Africans Asians more commonly have a deletion of two α genes on 1 chromosome (cis deletion) Africans more commonly have a deletion of 1 α gene from each chromosome (trans deletion) 3 gene deletion is associated with severe anemia 4 gene deletion is not compatible with life will cause hydrops fetalis β-thalassemia types 1 gene involvement called β-thalassemia minor chain may be truncated (β⁺) or deleted (β⁰) β/β⁺ is the most benign form may be caused by mutation in Kozak consensus sequence 2 gene involvement called β-thalassemia major β⁰/β⁰is the most severe form α,α,α,α hemoglobin present
Presentation
Symptoms α-thalassemia mild anemia in 2 gene deletion severe anemia in 3 gene deletion symptoms being at birth β-thalassemia minor form largely asymptomatic intermedia form hypochromic, microcytic anemia major form severe anemia symptoms begin after several months of life due to initial presence of HbF chipmunk facies secondary to extramedullary hematopoiesis in the skull Physical exam β-thalassemia major form hepatosplenomegaly due to chronic hemolysis, additionally exacerbated by extramedullary hematopoiesis in these organs
Evaluation
Peripheral smear 3 gene deletion α-thalassemia target, hypochromic, microcytic cells, with Heinz bodies from HbH β-thalassemia minor target, hypochromic, microcytic cells β-thalassemia major nucleated RBCs target, hypochromic, microcytic cells Hemoglobin gel-electrophoresis α-thalassemia trait normal 3 gene deletion α-thalassemia HbH (β,β,β,β) 4 gene deletion α-thalassemia Hb Barts (γ,γ,γ,γ) β-thalassemia minor ↑ HbA₂, HbF ↓ HbA β-thalassemia major ↑ HbA₂, HbF no HbA Imaging β-thalassemia major hair-on-end/crew cut appearance of the skull secondary to extramedullary hematopoiesis in the skull
Treatment
β-thalassemia major frequent transfusions required can cause iron overload and hemochromatosis

Prognosis, Prevention, and Complications
β-thalassemia major ↑ risk of B19-mediated aplastic crises Thalassemia trait protects against malaria