Lead poisoning affects heme synthesis, but significant anemia is unusual unless blood lead levels are markedly elevated Iron deficiency is common in children with increased lead levels and usually accounts for the microcytic anemia found in these patients If a concomitant hematologic disorder cannot be found in the anemic patient with plumbism, particular attention should be given to the possibility of severe lead intoxication Systemic Disease Numerous disorders that are not primarily hematologic may be associated with pallor and anemia due to decreased production of hemoglobin or red cells Occasionally, pallor is the only presenting finding of a serious systemic disorder Chronic inflammatory diseases, such as juvenile idiopathic arthritis (JIA) and ulcerative colitis, are often accompanied by a normocytic or microcytic anemia related to impaired iron utilization by hematopoietic cells The serum iron is reduced; however, low iron-binding capacity distinguishes this anemia of chronic inflammation from the anemia of iron deficiency Similar clinical and laboratory findings may be associated with chronic infections such as HIV and subacute bacterial endocarditis Other diseases in which anemia may be a prominent component include chronic renal disease, hyperthyroidism, and hypothyroidism The anemia in these disorders is not severe enough to be considered a hematologic emergency unless complicated by other hematologic abnormalities However, anemia may be the first clue to an underlying disease in which early treatment may improve the outcome substantially Increased Red Cell Destruction Numerous conditions associated with shortened red cell survival can be congenital, such as with hemoglobinopathies and membrane and enzyme defects Acquired causes of shortened red cell survival include autoimmune hemolytic anemia, drug-associated hemolytic anemias, disseminated intravascular coagulation (DIC), and hemolytic uremic syndrome (HUS) The hemoglobin levels in these disorders can be normal, slightly depressed, or so low as to be lifethreatening The steady-state hemoglobin concentration is determined by a balance between the severity of the destruction and the bone marrow’s ability to respond to the shortened red cell survival Compensation is achieved by an increase in erythrocyte production as is evident from the elevated reticulocyte count that is usually found in these conditions When the child with increased red cell destruction cannot compensate and make more red blood cells, this may result in a severe, life-threatening exacerbation of the underlying anemia (e.g., as is the case with acquired red cell