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Hypoproliferative anemias result from deficient erythropoietin (EPO) or a diminished response to it; they tend to be normocytic and normochromic. Renal, metabolic, and endocrine disorders are common causes. Treatment includes measures to correct the underlying disorder and sometimes EPO.
Hypoproliferation is a common mechanism in anemias of renal disease, hypometabolic or endocrine deficiency states (eg, hypothyroidism, hypopituitarism), and protein deprivation. The mechanism appears to be a relative or absolute decreased production of EPO. In hypometabolic states, the bone marrow may also fail to respond to EPO.
The deficiency in renal production of EPO and the severity of anemia correlate with the extent of renal dysfunction; anemia occurs when creatinine clearance is < 45 mL/min. Renal glomerular lesions (eg, from amyloidosis, diabetic nephropathy) generally result in the most severe anemia for their degree of excretory failure.
The term anemia of renal disease refers only to that caused by decreased EPO, but other mechanisms may increase its severity. In uremia, mild hemolysis is common; its basis is uncertain. Less common is RBC fragmentation (traumatic hemolytic anemia), which occurs when the renovascular endothelium is injured (eg, in malignant hypertension, membranoproliferative glomerulonephritis, polyarteritis nodosa, or acute cortical necrosis). Traumatic hemolysis in children can be an acute, sometimes fatal illness called hemolytic-uremic syndrome (see Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS)).
Diagnosis is based on demonstration of renal insufficiency and normocytic anemia, peripheral reticulocytopenia, and a paucity of erythroid hyperplasia for the degree of anemia. RBC fragmentation on the peripheral smear, particularly if there is thrombocytopenia, suggests simultaneous traumatic hemolysis.
Therapy is directed at improving renal function and increasing RBC production. If renal function returns to normal, anemia is slowly corrected. In patients receiving long-term dialysis, EPO, beginning with 50 to 100 units/kg IV or sc 3 times/wk with iron supplements, is the treatment of choice. In almost all cases, maximum increases in RBCs are reached by 8 to 12 wk. Reduced doses of EPO (about ½ the induction dose) can then be given 1 to 3 times/wk. Transfusions are rarely necessary. Careful monitoring of the response is needed to avoid adverse effects when Hb increases to > 12 g/dL.
Clinical and laboratory findings of other hypoproliferative normochromic-normocytic anemias are milder but otherwise mimic those of the anemia of renal disease. The mechanism of the anemia of protein depletion may be general hypometabolism. Hypometabolism may diminish the marrow response to EPO. Protein’s role in hematopoiesis is unclear.
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