Iron Accumulation
Each unit of red blood cells contains about 250 mg of iron complexed with hemoglobin, which is 100 times more than the quantity absorbed in the daily diet. Since the body has no mechanism for excretion of excess iron, iron overload can occur after as few as 10 transfusions. Transfusion hemosiderosis may become apparent after about 100 units of blood. Iron overload causes oxidative damage to the liver, heart, pancreas, thyroid, and other endocrine glands. Organ damage may already be advanced at the time of diagnosis. Organ toxicity begins when reticuloendothelial sites of iron storage become saturated and iron becomes deposited in other cells.
The most serious complication is cardiotoxicity, which may lead to arrhythmias, congestive heart failure and death. Hepatic injury, diabetes mellitus and adrenal insufficiency may also occur.
Serial ferritin monitoring is helpful in assessing total body iron burden. Treatment with iron chelation agents, such as parenteral deferoxamine, should be initiated early in the course of chronic transfusion therapy. Deferasirox is an oral iron chelator that can aid in management of iron overload. Long term maintenance of serum ferritin below 300 ng/mL is associated with improved survival.
Adverse effects of this drug include GI distress, auditory and ocular disturbances, hepatic and renal failure, and bone marrow suppression. The EPIC study demonstrated reduction in iron burden and a clinically acceptable safety profile in patients with sickle cell anemia (Br J of Haematol. 2011; 154; 387-397)
The best way to prevent iron overload is to limit the number of transfusions as much as possible. Multiple studies have demonstrated an improvement in iron overload after transition from simple transfusion to erythrocytapheresis (Transfus Med Hemother.2008; 35: 24-30; J Pediatr Hematol / Oncol. 1996; 18: 46-50; Blood. 1994; 83: 1136-1142). However, erythrocytapheresis is more expensive and may be associated with additional complications.
