Megaloblastic Anemia by Dr. Sookun Rajeev Kumar

Megaloblastic Anemia

1. MEGALOBLASTIC ANEMIA Dr. Sookun Rajeev K (MD) Dept of General Medicine Anna Medical College

2. DEFINITION: M egaloblastic anemia is associated with an abnormal appearance of the bone marrow erythroblasts in which nuclear development is delayed and nuclear chromatin has a lacy open appearance. There is a defect in DNA synthesis usually caused by deficiency of Vit B12 or folate

3. CAUSES OF MEGALOBLASTIC ANEMIA Diet Vitamin B12 deficiency : vegan diet, poor quality diet Folate deficiency : poor quality diet, old age, poverty, synthetic diet without added folic acid, goats’ milk

4. CAUSES OF MEGALOBLASTIC ANEMIA Malabsorption Gastric causes of vitamin B12 deficiency : pernicious anaemia , congenital intrinsic factor deficiency or abnormality, gastrectomy Intestinal causes of vitamin B12 deficiency : stagnant loop, congenital selective malabsorption, ileal resection, Crohn’s disease Intestinal causes of folate deficiency : coeliac disease, tropical sprue , jejunal resection

5. CAUSES OF MEGALOBLASTIC ANEMIA I ncreased cell turnover Folate deficiency : pregnancy, prematurity, chronic haemolytic anemia (such as sickle cell anemia ), extensive inflammatory and malignant diseases

6. CAUSES OF MEGALOBLASTIC ANEMIA Renal loss Folate deficiency : congestive cardiac failure, dialysis Drugs Folate deficiency: anticonvulsants, sulphasalazine

7. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY The manifestations appear after deficiency of vitamin B 12 has been present for 3-12 years. There is pallor of skin and mucous membranes .

8. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY The skin shows a lemon yellow tint due to mild jaundice. The tongue is smooth, atrophic, red and raw with loss of papillae and there is angular stomatitis .

9. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY The other features are : Anorexia Dyspepsia A lternating constipation and diarrhoea M ild hepatosplenomegaly .

10. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY The other features are : Purpura due to thrombocytopenia and widespread melanin pigmentation are less frequently observed. There may be infertility in young females. Other systemic features of anaemia may be present .

11. CLINICAL MANIFESTATIONS OF FOLIC ACID DEFICIENCY Folic acid deficiency manifests within a period of few weeks to months. Glossitis is less common than in vitamin B 12 deficiency.

12. CLINICAL MANIFESTATIONS OF FOLIC ACID DEFICIENCY Neurological features are very rare. Only depression, irritability, poor judgement , forgetfulness and sleep deprivation have been seen in some patients. Anorexia and occasional diarrhoea may be present .

13. INVESTIGATIONS VIT B 12 DEFICIENCY Blood Haemoglobin levels range from 3-9 g/dl. Mean corpuscular volume (MCV) is over 110 fl (normal 80-95). Mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) are usually normal .

14. INVESTIGATIONS VIT B 12 DEFICIENCY Blood Reticulocyte count is low in relation to degree of anemia . There is moderate leucopenia and thrombocytopenia. Peripheral smear shows oval macrocytes , macropolycytes , a few myelocytes and occasional normoblasts . In a severely anaemic patient, megaloblasts may be seen in the peripheral smear.

15. INVESTIGATIONS VIT B12 DEFICIENCY Bone marrow The cell trails of bone marrow smears are hypercellular with frequent mitoses and increased myeloid: erythroid ratio. The characteristic features are: presence of megaloblasts , giant bands and giant metamyelocytes .

16. INVESTIGATIONS VIT B12 DEFICIENCY Bone marrow Megakaryocytes are decreased with basophilic agranular cytoplasm and hypersegmented nucleus. Bone marrow iron store is increased and chromosome analysis of bone marrow cells and PHA-stimulated cultures shows multiple abnormalities.

17. INVESTIGATIONS FOLATE DEFICIENCY Folate deficiency Blood and marrow findings are as in B 12 deficiency. Serum folate is decreased below 3 µg/L and red cell folate is much lower, below 160 µg/L. Vitamin B 12 in serum is normal or borderline normal. Serum LDH is increased. Serum bilirubin is increased.

18. INVESTIGATIONS FOLATE DEFICIENCY Folate deficiency Abnormal deoxyuridine suppression test in bone marrow culture is corrected by addition of N-5 methyl-THF or other folate supplement. Increased excretion of formimmunoglutamate (FIGLU) in urine. Excess excretion of aminoimidazole carboxamide (AICAR) in urine. Jejunal biopsy reveals pathological lesions in the small intestine.

19. TREATMENT OF B 12 DEFICIENCY General management : This is similar to other cases of anaemia . For severe anaemia ( Hb < 4 g/dl), packed red cell transfusion is given slowly (15-30 drops/minute) along with a diuretic ( furosemide 40-80 mg). Before transfusion it is necessary to collect samples for B 12 and folic acid estimation. A bone marrow aspiration should also be performed before transfusion.

20. TREATMENT OF B12 DEFICIENCY Specific therapy : Hydroxycobalamin is given in doses of 1000 µg by deep subcutaneous/intramuscular injection twice in the first week and thereafter once a week for 6 weeks . Within 48 h after the first injection the bone marrow becomes normoblastic .

21. TREATMENT OF B12 DEFICIENCY Specific therapy : Within 2-3 days, reticulocyte count rises, reaching a peak between the fifth and tenth days and falls gradually to normal level on about the twentieth day. The leucocyte and platelet counts become normal in 7-10 days. Giant metamyelocytes persist up to 12 days in the bone marrow but macropolycytes disappear in 2 weeks .

22. TREATMENT OF FOLATE DEFICIENCY General management : The treatment of anemia is the same as that for vitamin B 12 deficiency.

23. TREATMENT OF FOLATE DEFICIENCY Specific therapy : Oral folic acid (5-15 mg/day) should be given. It is given prophylactically (350 µg/day) to all pregnant women, premature babies, patients receiving dialysis, and in severe and chronic haemolytic states. Folic acid should not be given alone in megaloblastic anaemia until vitamin B 12 deficiency has been excluded, since folate administration may precipitate neurological changes by aggravating methionine deficiency in the brain.

24. TREATMENT OF FOLATE DEFICIENCY Specific therapy : To patients receiving folic acid antagonists such as methotrexate, folinic acid is given daily orally (15 mg) or parenterally (3 mg/ml). Folinic acid mouth washes are employed to obviate oral side-effects of folate antagonists. Oral folic acid supplements can be used equally effectively. Megaloblastic anaemia due to other cytotoxic drugs which inhibit DNA synthesis is not cured by vitamin B 12 or folic acid therapy .

25. TREATMENT OF FOLATE DEFICIENCY Specific therapy : Patients treated with folic acid respond rapidly with a sense of well being; reticulocytosis occurs in 5-7 days, and there is total correction of haematologic abnormalities within two months . In severely anaemic patients in whom there is no clear-cut indication as to which deficiency is present, it is better to give both vitamin B 12 and folic acid. Moreover, co-existing infection, if any, should be treated.