Thalassemia syndromes

Diagnosis and management of Thalassemias

• Readily made during childhood
• Severe Anemia accompanied by the characteristic signs of massive
ineffective erythropoiesis
• Hepatosplenomegaly
• Profound microcytosis
• Elevated levels of HbF, HbA or both
• Charactersitic blood smear (insert pic)
• Many Patients require chronic hypertransfusion therapy to maintain a
hematocrit of at least 27-30% > erythropoiesis is suppressed
• Splenectomy required if the annual transfusion requirement increases
by 50%
• Folic Acid supplements
• Pnuemovax in anticipation of eventual splenectomy is advised
• Many Patients develop endocrine deficiencies as a result of iron
overload
Transfusional Hemosiderosis
• Chronic blood transfusion can lead to bloodborn infection,
alloimmunization, febrile reactions and lethal iron overload.
• A unit of PRBC = 250-300mg iron
• The iron assimilated by a single transfusion of 2 units of prbc is thus
equal to a 1 to 2 year oral intake of iron.
• Iron accumulates in chronically transfused patients because no
mechanisms exist for increasing iron excretion
• Vitamin C should not be supplemented because it generates free
radicals in iron excess states.
• Patients who receive >100 units of PRBCS usually develop
hemosiderosis
• Ferritin level rises, followed by early endocrine dysfunction ( glucose
intolerance and delayed puberty), cirrhosis, and cardiomyopathy.
• The decision to start long-term transfusion support should also
prompt one to institute therapy with iron-chelating agents.

• Deferoxamine ( Desferal ) – parenteral use. Its iron-binding kinetics

require chronic slow infusion via a metering pump.
• The constant presence of the drug improves the efficiency of
chelation and protects tissues from occasional releases of the most
toxic fraction of iron – low molecular weight iron
• Deferoxamine is relatively nontoxic. Occasional cataracts, deafness,
and local skin reactions, including urticaria, occur
• Skin reactions can usually be managed with antishistamines
• Negative iron balance can be achieved, even in the face of a high
transfusion requirement, but this alone does not prevent long term
morbidity and mortality in chronically transfused patients
• Deferasirox – oral iron chelating agent.
• Single daily doses of 20-30mg/kg produced reductions in liver iron
concentration comparable to deferoxamine in long term transfused
patients.
• Toxicities are similar to those of deferoxamine