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.