Macrocytic Anemias

includes megaloblastic and nonmegaloblastk causes Megaloblastic anemia

• Impaired DNA synthesis — cytoplasm matures faster than nucleus — ineffective erythropoiesis and macrocytosis; due to folate or B12 deficiency

• ✓ folate and vitamin B|2.* LDH & indirect bilirubin (due to ineffective erythropoiesis)

• Smear: neutrophil hypersegmentation. macro-ovalocytes, anisocytosis, poikilocytosis Folate deficiency

• Folate present in leafy green vegetables and fruit; total body stores sufficient for 2-3 mos

• Etiologies: malnutrition (alcoholics, anorectics, elderly), i absorption (sprue).

impaired metabolism (methotrexate, pyrimethamine, trimethoprim), t requirement (chronic hemolytic anemia, pregnancy, malignancy, dialysis)

• Diagnosis: i folate; 1 RBC folate.f homocysteine but nl methylmalonic acid (unlike B12


• Treatment: folate 1-5 mg PO qd; important to r 0 Br; deficiency Vitamin B12 deficiency

• Bu present only in foods of animal origin; total body stores sufficient for 2-3 y

• Binds to intrinsic factor (IF) secreted by gastric parietal cells; absorbed in terminal ileum

• Etiologies: malnutrition (alcoholics, vegans), pernicious anemia (autoimmune disease against gastric parietal cells, associated with polyglandular endocrine insufficiency and * risk of gastric carcinoma), other causes of I absorption (gastrectomy, sprue. Crohn's disease). T competition (intestinal bacterial overgrowth, fish tapeworm)

• Clinical manifestations: neurologic changes (subacute combined degeneration)

affecting peripheral nerves, posterior and lateral columns of the spinal cord, and cortex numbness, paresthesias. 1 vibratory and positional sense, ataxia, dementia

• Diagnosis: I B12; 1 homocysteine and methylmalonic acid; anti-IF Ab; Schilling test

• Treatment: 1 mg Bu IM qd x 7 d q wk ■ 4-8 wks q month for life neurologic abnormalities are reversible if treated w in 6 mos folate can reverse hematologic abnormalities of Bu deficiency but not neurologic changes oral supplementation (2 mg qd) appears feasible as well (Wood 1998:911191) Nonmegaloblastk macrocytic anemias

• Liver disease: often macrocytic, may see target cells

• Alcoholism: BM suppression & macrocytosis independent of folate Bjj defic. or cirrhosis

• Reticulocytosis

• Hypothyroidism

• Medications that impair DNA synthesis: zidovudine. 5-FU. hydroxyurea. Ara-C

• Metabolic disorders: hereditary orotic aciduria. Lesch-Nyhan syndrome

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