Megaloblastic anemia

basic info about megaloblastic anaemia and its treatment.

1. MEGALOBLASTIC ANEMIA

2. What is Megaloblastic anemia? Megaloblastic anemias are characterized by the presence of abnormally large developing red cells in the bone marrow. The marrow is usually cellular. Anemia is based on ineffective erythropoiesis . These red cells are large in shape

3. Etiology Cobalamin : Deficiency / abnormal metabolism. Folate : Deficiency / abnormal metabolism / antifolate drugs. Drugs interfering with synthesis of DNA. Rarely- orotic aciduria , AML, myelodysplasia . Arsenic poisoning Nitrous oxide inhalation.

4. Cobalamin / Vitamin B 12 Forms : Ado (2-deoxyadenosyl) form; found in mitochondria; Cofactor for Methyl Malonyl CoA Mutase . Methyl cobalamin ; found in plasma,cytoplasm ; Cofactor for Methionine synthase . Hydroxocobalamin

5. Absorption

6. Absorption

7. Proteins involved in active absorption are, Intrinsic factor { IF= HCl }. Haptocorrins . Cubilin . Transcobalamin II. TC I – cobalamin analogues. IFs are destroyed in illeal cells Cobalamin enters portal blood after 6 hrs of oral ingestion.

8. Amount recirculated in bile 0.5 - 5µg. Body stores 2-3mg. Sufficient for 3-4 years without dietary intake of cobalamin . Daily requirement: 1-3µg. Only traces are excreted in urine; in pharmacological doses large part is excreted in urine.

9. Causes of cobalamin defiency Nutritional –Vegans (legumes) Abnormalities - TC II deficiency; Congenital absence of IF Malabsorption Gastrectomy (total / partial) Tropical sprue Intestinal stagnant loop syndrome Selective malabsorption Ileal resection Crohn’s disease Pernicious anemia

10. Folate Destroyed easily by cooking especially in large amounts of water. Storage in liver (sufficient for 3-4 months) Total body folate around 10mg. Daily requirements: 200-300µg. Pregnancy: 400µg.

11. Absorption – Upper small intestine. Transport – Plasma protein bound 1/3. Considerable enterohepatic circulation occurs Alcohol interferes with the release of methyl-THFA by hepatocytes only traces are excreted; but in pharmacological doses 50-90% are excreted.

12. Epithelial surfaces: macrocytosis Infertility in both men and women CVD – IHD. Malignancy : Acute Lymphoblastic Leukemia of childhood. Neurologic : bilateral peripheral neuropathy and degeneration; Alzhiemer’s disease Maternal: prematurity; abortion; neural tube defects Children: poor brain development ; impaired intellectual development.

13. Haematological findings Oval macrocytes Anisocytosis (varied sizes ) Poikilocytosis ( abnormal shaped ) Hypersegmanted neutrophils Howell – jolly bodies Unconjugated bilirubin Haptoglobins Urine – urobilinogen , hemosiderin .

14. Howell jolly bodies are the basophilic nuclear remnants in the circulating erythrocytes

15. ELISA findings Serum cobalamin normal:160-1000 ng /L severe anemia <100ng/L Serum folate normal: 2µg/L-15µg/L Red cell folate normal: 160 - 640µg/L.

16. Treatment

17. Cobalamin : Hydroxocobalamin is preferred because it is more highly protein-bound and therefore remains longer in the circulation. Initial therapy should consist of 100–1000 mcg of vitamin B12 intramuscularly daily or every other day for 1–2 weeks to replenish body stores. Maintenance therapy consists of 100–1000 mcg intramuscularly once a month for life.

18. If neurologic abnormalities are present, maintenance therapy injections should be given every 1–2 weeks for 6 months before switching to monthly injections. Oral doses of 1000 mcg of vitamin B12 daily are usually sufficient to treat patients with pernicious anemia who refuse or cannot tolerate the injections. After pernicious anemia is in remission following parenteral vitamin B12 therapy, the vitamin can be administered intranasally as a spray or gel.

19. Folate : 5-15mg; for 4 months Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy.

20. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. Prophylactic folic acid foods – bread, wheat, rice. Potasssium supplements if needed. Antiplatelets if needed.

21. Non megaloblastic but macrocytic anemias RBC’s are round not oval There are no hypersegmented neutrophils and howell – jolly bodies

22. Macrocytosis without megaloblastosis

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