beta thalassemia major (Cooley's anemia)

Pathology

• absence of both beta-globin genes
• severe anemia requiring transfusions at an early age
• child is not anemic at birth because of the predominance of fetal hemoglobin
• transfusion-related iron overload
• hemolytic anemia

Clinical manifestations

• skeletal abnormalities:
  • results form hypertrophy & expansion of marrow
  • osteoporosis
  • maxillary overgrowth gives rise to facial appearance of Cooley's anemia
• hepatic changes:
  • enlarged liver due to extramedullary hematopoiesis
  • cirrhosis with nodular regeneration
  • iron deposition (iron overload from transfusions)
  • gallstones in 15% of patients over 15 years of age
• cardiopulmonary:
  • congestive heart failure secondary to severe anemia
  • myocardial hemosiderosis from transfusion overload
  • EKG changes
    • increased PR interval
    • premature ventricular contractions (PVC)
    • premature atrial contraction (PAC)
    • ST segment depression
  • pericarditis, sterile
  • pericardial effusion
• enlarged kidney
• splenomegaly in untransfused patients
• growth retardation
• hypogonadism

Laboratory

• complete blood count (CDV)
  • anemia: blood hemoglobin levels may drop below 4 mg/dL
  • child is not anemic at birth because of the predominance of fetal hemoglobin
  • MCV is low: microcytosis
• peripheral blood smear
  • microcytosis
  • target cells
• reticulocyte count is high: reticulocytosis
• hemoglobin electrophoresis:
  • hemoglobin F 10-90%
  • hemoglobin A2 7-90%
• evidence of hemolysis
  • increased serum LDH
  • increased serum bilirubin
• iron studies
  • serum ferritin is normal
  • serum iron, TIBC & % transferrin saturation are normal
• beta globin gene mutation

Diagnostic procedures

• echocardiogram is pulmonary hypertension suspected

Complications

• pulmonary hypertension (most common)

Management

• transfusion support
  • maintaining Hgb > 10 g/dL suppresses endogenous hematopoiesis & prevents skeletal abnormalities & cardiomegaly
• iron chelation
  • deferoxamine 40 mg/kg max 2 gm over 8 hours (IV)
  • few patients survive to adulthood without aggressive iron chelation or BMT
  • deferiprone (Ferriprox) for deferoxamine failure
• splenectomy for transfusion-dependent thalassemia
  • splenectomy reduces transfusion requirements
• bone marrow transplantation (BMT) for severe disease
• gene therapy
  • autologous CD34+ cells were transduced with a BB305 vector which encodes beta-globin with a T87Q amino acid substitution
  • cells were then reinfused after the patients had undergone myeloablative busulfan conditioning
  • this gene therapy procedure reduced or eliminated need for long-term packed RBC transfusions in 22 of 22 patients

More general terms

• beta thalassemia

Patient information

beta thalassemia major patient information