Thalassemia
- Group of disorders characterized by deletions (partial or total) or
modifications of globin chain genes
- Most cause microcytic hypochromic anemia
Alpha thal – defective or absent alpha chain synthesis; 4 genes on chromosome 16
- normal – all 4 genes present
- normal variant or silent carrier – 3/4 genes (can have mild microcytosis
or normal)
- trait – 2/4 genes (characterized by mild microcytic anemia & mild increase in RBC);
Bart hb (gammax4) detectable within 1st months of life, then fades
- Hgb H dz – 1/4 genes (characterized by lots of beta4 Hgb molecules = HbH),
mod-severe microcytic
anemia, splenomegaly, hyperbili, high retic); has some Hb Bart (more than 2
del dz)
- hydrops fetalis (Barts) – 0/4 genes; 80-90% Hb Bart, embryonic Hb acts as
O2 carrier, severe anemia, CHF, edema; usually stillborn
Beta thal – variable levels of beta chain synthesis; 2 genes on chromosome 11
Hemoglobin E: beta-chain variant (alpha2 / beta2, 26Glu->Lys);
prevalent in populations from Southeast Asia, particularly Thailand and Cambodia
- trait – no anemia, but microcytic
- homozygous – mild anemia, microcytic, no organomegaly
- E-beta-thalassemia – similar to beta-thalassemia major; characterized by
severe anemia, organomegaly from extramedullary hematopoiesis, and hemolysis;
requires RBC transfusion
Labs
- Mentzer Index
- The RDW in thalassemia, unlike iron deficiency,
is normal and may be a more accurate discriminant function in differentiating
between the two vs Mentzer index
- Make the diagnosis of beta-thalassemia with hemoglobin electrophoresis.
- Alpha-thalassemia will not show up on electrophoresis: it is diagnosed by
molecular diagnostic techniques.
- Think of Alpha thalassemia in Asians. Beta thal in Meditteraneans.
- Differential diagnosis for target cells on smear: beta thalassemia,
hemoglobin C disease, liver disease, beta-lipoproteinemia.
- In general you should not see targets in sickle cell unless they are
sickle-thalassemia or sickle-C.
back to Anemia, General Approach
from CHLA board review 2005