Although a complete review of all of the mechanisms leading to anemia is beyond the scope of this chapter, an appreciation of some of the mechanisms is useful before approaching the diagnosis of anemia in adults and children. Three broad categories of anemia are blood loss anemia, hypoproliferative anemia, and hemolytic anemia.
Blood Loss Anemia
Blood loss may occur acutely or chronically. When blood is lost acutely through hemorrhage, it may take several hours before a decline in hemoglobin concentration is observed because of the time required for restoration of the plasma volume and equilibration. Several days may elapse before an appropriate reticulocytosis is noted. Chronic blood loss ultimately leads to hypoproliferative anemia because of iron deficiency. In most of the latter patients, the underlying cause of the chronic blood loss is usually more determinative of prognosis than the anemia itself.
Hypoproliferative Anemia
When used broadly, the term hypoproliferative anemias refers to entities that manifest as an inability to produce an adequate number of erythrocytes in response to appropriate signals. Although there are many different causes, the hallmark of hypoproliferative anemia is a low reticulocyte count (Table 1). The etiology underlying this class of disorders may relate to the hypoproliferation of precursors within the BM, such as may be seen in aplastic anemia, when there is BM replacement (myelophthisis), or where there is ineffective erythropoiesis, due to abnormal maturation of precursors in the BM, as is encountered in thalassemia, megaloblastic anemia (folate deficiency, vitamin B12 deficiency, myelodysplastic syndromes [MDSs]), and others. In thalassemia and megaloblastic anemia, the BM often is packed with early erythroid progenitors. However, intramedullary demise of precursors prevents the formation and release of mature RBCs.
Table1. Usefulness of the Reticulocyte Count in the Diagnosis of Anemia a
By far the most common cause of hypoproliferative anemia glob ally is iron deficiency. It is estimated that about 2% of infants and children may become iron deficient purely because of inadequate dietary intake. About 4% of women ages 20 to 49 years of age in the United States have iron-deficiency anemia primarily because of inadequate dietary intake in the setting of menstruation and childbirth. Iron deficiency is also commonly encountered in older individuals as well (~2% of individuals older than age 50 years), and it should provoke a thorough search for its etiology, which in both men and non-menstruating women frequently is gastrointestinal blood loss. After iron deficiency, acute or chronic inflammation and renal disease are common etiologies of anemia. BM failure states and BM replacement caused by hematologic malignancies or solid tumors are less common causes of anemia and are often accompanied by other hematologic manifestations, such as leukopenia and thrombocytopenia.
Hemolytic Anemia
The causes of hemolytic anemia are quite varied and may be congenital or acquired. The hallmark of hemolytic anemia is an elevated reticulocyte count (see Table 1). However, if hemolysis occurs in a setting where erythropoiesis is also suppressed or ineffective, the reticulocyte count may not be as high as expected for the degree of anemia. Other features commonly associated with hemolytic anemia include an elevated LDH level, increased unconjugated (indirect) bilirubin level, and decreased haptoglobin level. Hemolytic anemia also may manifest with distinctive changes on the peripheral blood smear (e.g., spherocytes, sickle cells, or schistocytes). Congenital causes include the hemoglobinopathies, enzymopathies (predominantly glucose 6-phosphate dehydrogenase [G6PD] deficiency), and membrane dis orders. Acquired conditions include autoimmune hemolytic anemia, microangiopathic hemolytic anemia, hemolysis related to infections, and acquired membrane disorders such as those caused by liver disease (spur cell of anemia) and paroxysmal nocturnal hemoglobinuria.
