Thalassemias Flashcards
How many alpha and beta globulin genes are present in a normal human’s genome?
Four copies of alpha, two on each chromosome 16. There are only two copies of each beta-like globulin, one on each chromosome 11, but 6 total (2 x beta, delta, gamma).
What CBC results and a morphological feature of thalassemia RBCs?
Dec MCV, dec MCH, normal RDW (smaller RBCs, but uniform in size), inc total RBC, inc retic. Also increased RBC contents: unconjugated bilirubin, lactate dehydrogenase (LDH), AST. Swollen spleen, increased gall stones. Target cells, which have normal membrane areas but decreased volume, leading to excess, warped membranes.
Levels of what metal are of concern in thalassemias?
Iron. Iron absorption can be greatly increased in severe thalassemias, and transfusions will add additional iron. Iron overload may result in growth delay and endocrinopathies.
What are the types of alpha thalassemias?
No deletions - normal; 1 gene deletion - clinically silent; 2 gene deletions - thalassemia trait, microcytosis and possible anemia; 3 gene deletions - microcytic anemia (Hb H disease); 4 gene deletions - hydrous fetalis (fatal).
At what stage does thalassemia interrupt regular life and what are the features of this stage?
Hb H disease (three gene deletion). Hypochromic, microcytic anemia (Hb 7-10), inc retic, anemia exacerbated by vitamin deficiencies or infections (marrow overload). Enlarged spleen, cholelithiasis, iron overload.
How is alpha thalassemia diagnosed?
RBC morphology is only first hint - microcytosis (2 gene deletion), microcytosis + anemia (3 gene deletion). Hemoglobin electrophoresis is inconclusive (same proportion HbA (a2b2) and HbA2 (a2d2)) Only DNA sequencing for deletions is definitive.
How is alpha thalassemia treated?
Most require no therapy. Hb H disease needs some transfusions. Genetic counseling for asian –/++ form, may require in utero marrow transplant for fetal hydrops.
How is beta thalassemia diagnosed?
Microcytic cells are suggestive of thalassemia. Hemoglobin electrophoresis can show difference between beta globulin and delta globulin, thus differences between HbA (a2b2) and HbA2 (a2d2) will be seen and are diagnostic of Beta-thalassemia. B-thal major (Cooley’s anemia) will show no HbA.
What are the three classes of B-thalassemia and what genotypes correspond to each?
Thalassemia minor - Heterozygous Norm + B+, B0, dB; Thalassemis intermedia - Homozygous B+, dB, B+B0, E; Thalassemia major - B0B0 or EB0
What are the clinical signs of b-thalassemias?
B-Thal trait (minor) - minor or no anemia (dec MCV, MCH, inc RBC); B-thal intermedia - moderate anemia (Hb 7-10) anemia may be exacerbated, possible spenomegaly, growth delay, inc iron abs; B-thal major(Cooley’s, HbEB0) all of intermediate plus severe transfusion dependent thal.
How is beta-thalassemia (Cooley’s anemia) treated?
Transfusion therapy - maintains HGB 9-10, causes iron overload; Induction of fetal hemoglobin - hydroxyurea therapy, butyrate therapy; Bone marrow transplant - standard of care in Cooley’s anemia (B0-thal)
What is microcytosis also associated with?
Microcytosis results from both thalassemias (alpha and beta) and from iron deficiency. The cause of the condition must be determined because iron deficiency is treated with iron supplementation, whereas thalassemias increase iron absorption and risk iron overload even without iron supplements. Mutually exclusive treatments.
What CBC readings can help differentiate Fe deficiency from thalassemia?
RBC will be diminished in Fe deficiency, and elevated in thalassemia. RDW will be increased in Fe deficiency (fewer cells, random sizes) and normal in thalassemia (lots of cells, all the same size). Low iron levels can mask B-thalassemia b/c HbA takes all of the iron first, leaving little for HbA2, decreasing its level to “normal” in electrophoresis.
