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ANEMIA, a decreased hemoglobin/hematocrit level. Symptoms, which depend on the level of anemia and the time span in which this abnormality developed, include fatigue, shortness of breath, weakness, lightheadedness, and angina. Associated physical findings include tachycardia, tachypnea, and pallor. Patients with a chronic, slow-developing anemia may be extremely well compensated, and may therefore be relatively asymptomatic despite remarkably low levels of the hemoglobin and hematocrit. Patients may manifest systolic hypertension with a wide pulse pressure, which reflects an increased cardiac output. A common iatrogenic cause among hospitalized patients is volume overload with a resultant dilutional anemia. Anemia may result from decreased production of red blood cells or from increased peripheral loss of red blood cells. This distinction may be made by determining the reticulocyte index. An elevated reticulocyte index is associated with increased peripheral blood loss, either bleeding, most commonly, or hemolysis. If the site of bleeding is not obvious, then potential causes such as the gastrointestinal tract or the female reproductive system should be investigated. Hemolysis is suggested by the finding of an anemia with an elevated reticulocyte index associated with an elevated LDH and hyperbilirubinemia. The reticulocyte index is determined by the following equation:
A reticulocyte index greater than 3 indicates an appropriate marrow response which is seen with blood loss and hemolysis. If the reticulocyte index is less than 3, indicating a poor marrow response, then there is a decrease in red cell production, and the underlying cause must be determined. The MCV is helpful in determining the cause of a low reticulocyte anemia. These anemias are classified as microcytic, macrocytic, and normocytic when associated with a decreased, elevated, or normal MCV, respectively. The various anemias associated with decreased red cell production are discussed in the following.
MICROCYTIC anemia is caused by a number of etiologies to include iron deficiency, thalassemia, sideroblastic anemia, lead intoxication, and hookworm infestation. Iron deficiency anemia and thalassemia are the two major etiologies to distinguish. Iron deficiency anemias are associated with an elevated RDW, as opposed to thalassemias, which are associated with a normal RDW. Also, thalassemias often have a significantly decreased MCV disproportionate to the level of anemia. Once iron deficiency is diagnosed, internal bleeding must be ruled out. Sideroblastic anemia may be congenital or acquired, and it is diagnosed by finding ringed sideroblasts on bone marrow examination. Hookworm infestation induces an iron deficiency anemia that is secondary to gastrointestinal blood loss from the feeding parasites, and not the result of a hemorrhaging gastrointestinal structural abnormality such as polyps, malignancies, angiodysplasia, inflammatory bowel disease, Meckels diverticuli, or bleeding diverticuli. Lead intoxication may be distinguished by a black line noted on the gums (lead line) during physical exam and an elevated serum lead level.
NORMOCYTIC anemia is caused by a number of causes including chronic disease, malignancy, hypothyroidism, aplastic anemia, chronic renal failure, myeloid metaplasia, and multiple myeloma. The various etiologies are usually inferred by other associated lab or physical abnormalities. The anemia of chronic renal failure is secondary to decreased erythropoietin production by the diseased kidneys, and this anemia will often improve to some degree with exogenous erythropoietin therapy. Erythropoietin is administered subcutaneously 50-100 U/kg three times per week with concomitant iron therapy. Multiple myeloma should be aggressively ruled out in patients of the appropriate age group, as one-third of patients afflicted with this disease present with no abnormalities other than a normocytic anemia.
MACROCYTIC anemia is caused by a number of etiologies including chemotherapeutic agents, B12 deficiency, folate deficiency, liver disease, alcoholism, reticulocytosis, and infestation with Diphyllobothrium latum (fish hookworm). Examination of the peripheral smear may show one of two different types of macrocytosis. Oval macrocytes are associated with vitamin B12 deficiency, folate deficiency, myelodysplastic syndromes, and DNA synthesis blockade by chemotherapeutic agents. Round macrocytes are seen when alcohol, liver disease, or hypothyroidism is the underlying etiology. Patients should not be given empiric therapy with folate until the underlying cause has been determined. Patients with underlying B12 deficiency who are treated with folate may have resolution of the associated anemia; however, the neurologic damage associated with B12 deficiency will continue. Persons afflicted with HIV and treated with AZT often manifest a macrocytic anemia. Artifactual macrocytosis (an elevated MCV with no reticulocytosis and no macrocytes noted on peripheral smear) occurs in the presence of serum cold agglutinins, leukocytosis, hyperglycemia, and hypernatremia. Reticulocytosis of any cause may lead to an increased MCV.