Lecture 19 Beta Thalassemias

Question 1

Beta Thalassemia

Answer 1

• reduction in rate of synthesis of one or more of beta globin chains producing a microcytic/hypochromic anemia
• leads to imbalanced globin chain synthesis -> decreased RBC (and precursors) survival
• bone marrow enlargement
• excess alpha chains and iron accumulation cause of clinical manifestations
• only single beta chain inheritance from each parent
• caused by point gene mutations

Question 2

Beta Thalassemia cont’d

Answer 2

• Hb A marked decrease or absent resulting in macrocytic, hypochromic RBCs
• Hb F produc’n normal in utero but decreased production of beta chains during the 4th to 6th month may reactivate gamma chain production and increase in HbF
• in B chain hetero, there is increase in HbA2 due to decrease in Hb A and increase in delta chains
• iron excess mostly due to multiple blood transfusions

Question 3

Beta Thalassemia symptomology

Answer 3

• ineffective eythropoiesis
• hemolysis (shortened survival)
• iron accumulation causing RBC cellular and organ damage
• reduced hemoglobinization of RBCs (reducing O2 carrying capacity)

Question 4

Beta Thalassemia Major (Cooley’s Anemia)

Answer 4

• four genotypes identified:
  
  • homozygous B: Bo/Bo
  • homozygous B+ (mediterranean severe form): B+/B+
• dble hetero: Bo/B+
• homozygous (dB)Lepore: (dB)Lepore/ (dB)Lepore

Question 5

Hb Lepore

Answer 5

• composed of normal alpha genes and a fused dB genes
• when homozygous result is:
  
  • no normal d or B genes
  • no production of HbA or HbA2
• insufficient oxygenation causes hi levels of erythropoietin and erythroid hyperplasia in bone marrow
• enlarged erythron but few RBCs reach circulation
• massive bone expansion -> skeletal deformities
• hepatosplenomegaly
• folate deficiency from increased RBC produc’n
• adequate transfusion program allows children to grow and develop normally with no abnormal physical signs

Question 6

Beta Thalassemia Major Lab Findings and Disease Correlation

Answer 6

• microcytosis, hypochromasia, and marked anisopoikilocytosis
• numerous NRBCs, target cells and basophilic stippling present
• reticulocyte response is inadequate
• leukocytes usually increased
• platelet count normal
• bone marrow is hypercellular with erythroid hyperplasia
• Hgb electrophoresis, Hb F and Hgb A2 testing needed to confirm which of the 4 types is present

Question 7

B Thal Major Chem Testing

Answer 7

• incr. indirect bilirubin
• urine urobilinogen and fecal urobilin may be increased
• LDH incr. due to RBC hemolysis
• haptoglobin and hemopexin decr.
• ferritin, serum iron and transferrin saturation all incr. due to iron overload

Question 8

B Thal Major Treatment and Prognosis

Answer 8

• w/o treatment, death in the 1st or 2nd decade of life
• RBC transfusions main form of treatment
• iron overload major cause of late mortality (iron chelating helpful)
• w/o chelation, death in 2nd or 3rd decade due to hemosiderosis induced heart disease

Question 9

B Thalassemia Intermedia

Answer 9

• milder than thal major, more severe than thal minor
• clinical severity determines grouping as genetic defects variable
• overlap between intermedia and major
• impaired B chain synth less than major and excess a chains reduced
• homozygous B+/B+ “mild” B thalassemia alleles result in intermedia
• decreased severity due to:
  
  1. coexistent a thal which produces less excess a chains
  2. elevated gamma chain produc’n such as seen in HPFH; sustained produc’n of Hb F means less excess a chains

Question 10

B Thalassemia Intermedia Clinical Presentation

Answer 10

• relatively normal growth to more severe transfusion support types
• usually present with anemia and symptoms later than B thal major
• may include pallor, mod splenomegaly but less severe than B thal major
• iron overload may be present regardless of transfusion due to incr iron absorp’n

Question 11

B Thal Intermed Lab Findings and Disease Correlation

Answer 11

• Pts generally do not receive transfusions
• RBCs microcytic/hypochromic with anisopoikilocytosis
• target cells, basophilic stippling and NRBCs usually present
• bone marrow shows erythroid hyperplasia

Question 12

B Thal Minor (Trait)

Answer 12

• inheritance of abnormal single allele
• little or no anemia
• only rare clinical symptoms
• peripheral blood RBC morphology abnormal
• normal life span with no required treatment
• microcytic, hypochromic, with anisopoikilocytosis
• target cells and basophilic stippling usually present
• RBC count normal or increased
• NRBCs usually not present

Question 13

B Thal Minima (Silent Carrier)

Answer 13

• no clinical or lab abnormality
• discovered accidentally and during family studies
• DNA testing req’d for confirmation

Question 14

Hereditary Persistance of Fetal Hemoglobin (HPFH)

Answer 14

• caused by deletion or inactivation of either the d or B gene complex
• synthesis of gamma chains continues in adult life presenting clinical abnormalities
• incr. Hb F levels in adults
  Heterozygotes:
• normocytic, normochromic
• slightly incr RBC count
• near normal Hgb and Hct
• Hgb electrophoresis: Hb F 15-35%
  Homozygotes:
• slight microcytic, hypochromic RBCs
• RBC count incr due to incr affinity of HbF
• Hgb electrophoresis: Hb F 100%

Question 15

dB Thalassemia

Answer 15

• cause by reduced (dB)+ or absent (dB)o output of d and B chains
• incr produc’n of gamma chains present but less than in HPFH
• RBC morphology abnormal with anemia
  Homozygous (dB)o/ (dB)o:
• milder than B thal major (Cooley’s)
• only HbF present
  Heterozygous (dB)0 / B:
• clinically and hematologically similar to B thal minor; HbF higher and HbA2 normal