Megaloblastic Anemia
Dr.Singaram.A
Effect of cobalamin and folate on DNA synthesis
Actions of cobalamin
Vitamin B12
• Red Vitamin
• Animal products (meat and dairy products) provide the only dietary source of Vit.B12 for humans.
• RDA - 0.5 mcg/day
Cobalamin (Cbl) absorption.
Vitamin B12
• Adequate absorption of cobalamin depends upon five factors:
1. Adequate dietary intake2. Acid-pepsin in the stomach3. Pancreatic proteases4. Gastric secretion of a functional intrinsic
factor5. An ileum with functioning B12-IF receptors
Vitamin B12 deficiency
• Inadequate Vitamin B12 Intake• Impaired Intestinal Absorption
-regional enteritis, neonatal necrotizing enterocolitis, or celiac disease-Bacterial overgrowth-fish tapeworm – D.latum-Surgical removal of terminal ileum
• Imerslund-Grasbeck syndrome - defects in amnionless (AMN) or cubilin (CUBN) genes
Rare causes…
Pernicious anemia is extremely rare in children younger than 10 years.
• Congenital IF deficiency• Gastric surgery• Pancreatic insufficiency• Hereditary orotic aciduria• Thiamine responsive megaloblastic anemia
Folic Acid
• Occurs in animal products and in leafy vegetables in the polyglutamate form
• RDA – 50-150 mcg/day
Folic Acid deficiency
• Inadequate folate Intake• Increased requirements (infancy and early
childhood, chronic hemolysis, infections) • Goat’s milk• Decreased Folate Absorption
-chronic diarrheal states or diffuse inflammatory disease
• Drug induced:anticonvulsant drugs (e.g., phenytoin, primidone, phenobarbital) , methotrexate, pyrimethamine, trmethoprim
Clinical Manifestations
• Anemia, anorexia, irritability, easy fatigability
• Hyperpigmentation of knuckles and terminal phalanges.
• Neurologic signs may precede onset of anemia – loss of position and vibration sense (earliest)
Investigations - Hemogram
• Macrocytic RBCs (MCV >110 fl) and cytopenias
• Hypersegmented neutrophils
Folate levels
• Serum folate levels are primarily a reflection of short-term folate balance
• serum folate - >4 ng/mL : folate deficiency is effectively ruled out.
• serum folate <2 ng/mL : diagnostic of folate deficiency
• Red cell folate concentration is theoretically a more reliable indicator of tissue folate adequacy
Cobalamin levels
• >300 pg/mL — normal result; Cbl deficiency is unlikely
• 200 to 300 pg/mL— borderline result; Cbl deficiency possible.
• <200 pg/mL— low; consistent with Cbl deficiency (specificity of 95 to 100 percent)
Schilling test
Schilling test
TestGastrectomy,
pernicious anemia
Celiac disease*Bacterial
overgrowthIleal resection
or disease•Pancreatic
insufficiency
Vitamin B12 Low Low Low Low/normal Low
Vitamin B12 + intrinsic factor
Normal Low Low Low/normal Low
Vitamin B12 + antibiotics
n/a Low Normal Low/normal Low
Vitamin B12 + gluten-free diet
n/a Normal n/a Low/normal Low
Vitamin B12 + pancreatic enzymes
n/a n/a n/a n/a Normal
Bone Marrow Examination
• Erythroid hyperplasia; Nuclear – cytoplasmic asynchrony
• Granulocytic precursors - giant metamyelocytes and band forms
Treatment
• Cobalamin deficiency – Parenteral (i.m) – 1000 mcg daily for 1 week, weekly for next 4 weeks (until hematocrit becomes normal)
• Pernicious anemia and malabsorption – Monthly cobalamin supplementation.
• Erratic absorption with oral formulations
• Folate deficiency - folic acid(1 to 5 mg/day orally) for 3 – 4 weeks