Anemia - megaloblastic

Definition

Megaloblastic anemia is a term used to describe disorders of impaired DNA synthesis in hematopoietic cells but affects all proliferating cells.

Etiology:

• • Almost all cases are due to folic acid and vitamin B12 deficiency.

  • Folate deficiency arises from negative folate balance arising from malnutrition, malabsorption, or increased requirement (pregnancy, hemolytic anemia).

  • Pts on slimming diets, alcoholics, elderly, psychiatric Pts are at risk of nutritional folate deficiency.

  • Pregnancy and lactation need 3 x - 4 x daily folate needs. It is common to see dimorphic anemia picture (combined folate and iron deficiency).

  • Folate malabsorption is seen in celiac disease.

  • Drugs can interfere with folate absorption: ethanol, TMP, pyrimethamine, diphenylhydantoin, barbiturates, and sulfasalzine.

  • HD patients need enhanced folate intake because of folate losses.

  • Pts with hemolytic anemia, such as sickle cell anemia, required increased folate for accelerated erythropoiesis and can present with aplastic crisis (rapidly falling RBC counts) with folate deficiency.

  • Vitamin B12 deficiency occurs insidiously over 3 or more years, because daily vitamin B12 requirements are low (1-3 mg/d), whereas total body stores are 1-3 mg. Causes:

    • Partial or total gastrectomy and pernicious anemia.

    • Gastric atrophy in elderly patients, resulting in impaired vit B12 absorption.

    • Pernicious anemia occurs in people older than 40 years (mean onset 60 years. 30% have FH. It is associated with other autoimmune disorders: Graves' dz, Hashimoto's thyroiditis, and Addison's disesase). 90% of patients with pernicious anemia have antiparietal cell IgG antibodies and 60% have anti-intrinsic factor antibodies.

    • Other etiologies include pancreatic insufficiency, bacterial overgrowth, and intestinal parasites (Diphyllobothrium latum).

Dx:

• • Fatigue, sleep deprivation, irritability, depression, or forgetfulness in folate deficient patients.

  • Folate def does not cause neurological problems.

  • Vit B12 def: neurological findings - peripheral neuropathy most common manifestation including paresthesiae, lethargy, hypotonia, and seizures. Dementia.

  • Also Vit B12 def causes glossitis and diarrhea.

  • Malnourished patient, pigmentation of skin creases and nail beds, or glossitis. Jaundice or splenomegaly may indicate ineffective and extramedullary hematopoiesis. Decreased vibratotry and positional sense, ataxia, paresthesia, confusion, and dementia.

  • Neurological manifestations can occur even in the absence of anemia and may not fully resolve despite adequate treatment.

Dxtic:

• • CBC shows macroovalocytes (large MCV), anisocytosis with hypersegmented neutrophils (>5 nuclear lobes), leukopenia, and thrombocytopenia.

  • ▲ LDH, ▲ indirect bilirubin are elevated.

  • ▼ Reticulocytes.

  • ▼ Sr. B12 level. In upto 30% cases B12 will be normal because transcobalamin is an acute phase reactant and any form of stress can raise it. Serum methylmalonic acid (MMA) level: is raised. Order MMA if B12 level is normal and you suspect def.

  • ▲ Homocysteine and ▲ MMA in vitamin B12 deficiency; only ▲ homocysteine in folate deficiency.

  • If B12 is low, methylmalonic acid level is raised check antiparietal cell abs and anti-intrinsic factor abs.

  • RBC folate level should be checked as it is more accurate than serum folate, particularly if measured after folate therapy or improved nutrition has been initiated.

  • Schilling test is not done any more.

  • Antibodies to intrinsic factor is specific for diagnosis of pernicious anemia.

Dxtic procedures:

Bone marrow Bx may be needed to differentiate MDS or acute leukemia since they may present like megaloblastic anemia.

Tx:

• • Replace folate and vitamin B12.

  • Potassium supplementation may be necessary when treatment is initiated to avoid potentially serious arrhythmias due to hypokalemia induced by enhanced hematopoiesis.

  • Reticulocytosis should begin <1 wk of therapy, followed by a rising Hb over 6-8 wks.

  • Tx coexisting iron deficiency.

  • Folic acid, 1 mg PO qd, until the deficiency is corrected. High doses of folic acid, 5 mg PO qd may be needed in malabsorption syndromes.

  • Vit B12 deficiency is corrected by administering cyanocobalamin. Unless patient is severely ill (decompensated CHF due to anemia, advanced neurologic dysfunction), treatment with full doses of cyanocobalamin, 1 mg/d IM should await final lab dx.

  • After 1 wk of daily tx; f/up 1 mg/wk x 4 wks, then 1 mg/mo for life.

  • Pt. who decline to take parenteral therapy can be prescribed oral tablets or syrup at 50 mg PO daily for life.