Thalassemias Flashcards
Thalassemia’s other names
Hereditary leptocytosis, Mediterranean anemia
Cause of Thalassemia
Reduction or total absence of synthesis of one or more globin chains
Most clinically significant mutations
α-globin and β-globin gene mutations
Geographic distribution of Thalassemia belt
Thalassemia belt extends from Mediterranean to Southeast Asia and Northern Africa
Relation to malaria
Thalassemia minor imparts resistance to malaria
Clinical findings suggesting Thalassemia
Pallor (due to anemia), jaundice (due to hemolysis), splenomegaly (due to sequestration and hemolysis), skeletal deformities (due to bone marrow expansion)
Thalassemia findings in untreated β-thalassemia major
More prominent skeletal deformities due to massive expansion of bone marrow cavities
Cause of clinical manifestations in Thalassemia
Decreased or absent production of globin chains, unequal production causing imbalance in α/β chain ratio
Effect of α/β chain imbalance in Thalassemia
Leads to marked decreased survival of erythrocytes and their precursors
Mechanism of shortened RBC survival in Thalassemia
α/β chain imbalance determines clinical severity, different mechanisms in β-thalassemia and α-thalassemia
Complete Blood Count (CBC) expected findings in Thalassemia
↓ Hb, ↓ Hct, ↓ MCV, ↓ MCH, ↓ MCHC, Slight to moderate ↑ Reticulocyte count
Peripheral Blood Smear findings in Thalassemia
Varying degrees of microcytosis, hypochromia, target cells, anisocytosis, NRBCs, poikilocytosis, RBC inclusions (basophilic stippling, Howell-Jolly bodies, Pappenheimer bodies, Hb H inclusion bodies)
Iron studies in Thalassemia (to rule out IDA)
Serum ferritin and serum iron: Normal or ↑, TIBC: Normal
Confirmatory tests for Thalassemia
Molecular genetic tests
Alpha Thalassemia cause
Typically caused by a deletion of one, two, three, or all four of the α-globin genes, resulting in reduced or absent production of α chains
Normal genotype for Alpha Thalassemia
aa/aa
Silent carrier state in Alpha Thalassemia
One out of four genes deleted, genotype: -a/aa, asymptomatic
Two of four genes deleted (–/aa or -a/-a), mild microcytic hypochromic anemia
Alpha Thalassemia Trait (a-thalassemia minor)
Three of four genes deleted (–/-a), microcytic hypochromic anemia
Hb H Disease
Hb H disease predominantly seen in neonates
Hb Bart
Most severe form of alpha thalassemia, caused by deletion of all four alpha globin genes (–/–)
Hb Bart hydrops fetalis syndrome (alpha thalassemia)
Fetus survival in Hb Bart syndrome
Rare survival with intrauterine transfusion and neonatal intensive care
Survivors of Hb Bart syndrome
May require severe transfusion-dependent anemia treatment like β-thalassemia major
Treatment options for Hb Bart syndrome
Bone marrow transplant or cord blood transplant may be helpful
Beta thalassemia mutation cause
Mutations in β-globin gene complex
Normal genotype for β-globin gene
B/B
Silent carrier state in β-thalassemia genotype
β silent / β
β-thalassemia trait genotype
β+ / β or β0 / β
Silent carrier β-thalassemia remarks
Asymptomatic, normal hematologic parameters
β+ / β or β0 / β remarks
Asymptomatic, mild hemolytic anemia, microcytic, hypochromic RBCs
Most severe form of beta thalassemia genotype
β+ / β+ or β0 / β0
β-thalassemia major (Codey’s anemia) characteristics
Severe hemolytic anemia, microcytic, hypochromic RBCs, transfusion-dependent
Peripheral blood smear findings in β-thalassemia major
Target cells, teardrop cells, elliptocytes, nucleated red cells, polychromasia, basophilic stippling, Howell-Jolly bodies, Pappenheimer bodies
β-thalassemia major patient features
Frontal bossing, prominence of cheekbones and upper jaw, ‘hair on end’ skull appearance
Cause of iron accumulation in β-thalassemia major
Regular RBC transfusions
β-thalassemia intermedia genotypes
βsilent / βsilent, β+ / βsilent, β0 / βsilent
Clinical symptoms of β-thalassemia intermedia
Moderate symptoms, transfusion-independent, mild to moderate hemolytic anemia, microcytic, hypochromic RBCs
Definition of β0 mutation
β-globin gene mutation where no β chains are produced
Definition of β+ mutation
β-globin gene mutation resulting in 5% to 30% reduction in β chain production
Definition of βsilent mutation
β-globin gene mutation causing mildly decreased β chain production
