• 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.
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