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Megaloblastic Anemia
•Cytological and functional •abnormalities in peripheral •blood and bone marrow cells
due to impaired DNA synthesis.
Megaloblastic Anemia
The Megaloblastic anemia are caused by impaired DNA synthesis and almost always due to a deficiency of either B12 or Folate
(Megaloblastic Anemia ( clinical features
The onset is usualy insidious and the patient have symptoms of anemia, have slight yellow tinge due to hemolysis Inceased ineffective erythropoisis .red and sore tongue ,slight splenomegaly. In severe cases pancytopenia
Megaloblastic Anemia
In Vit b12 deficiency , there may be neurological symptoms and other signs including optic atrophy, prepheral neuropathy, subacute combined degeneration of
the cord and dementia
Megaloblastic Anemia Hematologic features
Macrocytic anemia
RBC Macro-ovalocytes
Reticulocytosis
Pancytopenia
Hypersegmented poly
Nucleuted RBC in PBS
Drugs causing Megaloblastic anemia
-mechanism Uncertain
Anticonvulsant drugs Oral contraceptive agents
- Dihydrofolate reductase inhibitors
Methotrexate
Trimethoprim
Triameterene
Pyrimethamine
VitB12 Folate
Content in food : Vegatables:poor Vegatable :richMeat : rich Meat : moderate
Effect of cooking : 10-30% loss 60-90% loss
Adult daily requirments 2-4 ug 200ug
Adult daily intake 5 -30 u g 100-500 u g
Site of absorption Ileum Duodenum & Jejunum
Body stores 2-5 mg 5-20 mg
Vitamin B 12 and Folate metabolism -----------------------------------------------------
------------------------------------- -
VitB12 Folate
Content in food : Vegatables:poor Vegatable :richMeat : rich Meat : moderate
Effect of cooking : 10-30% loss 60-90% loss
Adult daily requirments 2-4 ug 200ug
Adult daily intake 5 -30 u g 100-500 u g
Site of absorption Ileum Duodenum & Jejunum
Body stores 2-5 mg 5-20 mg
Vitamin B 12 and Folate metabolism -----------------------------------------------------
------------------------------------- -
Mechanism Disorder------------------------------ - Decreased intake Nutritional deficiency
Impaired absorption
Gastric causes : Pernicious anemiaGastrectomy
Intestinal causes Lesions of small intestine
Celiac disease
Tropcal sprue
Fish Tape worm infestation
Megaloblastic anemia due to Vit B12 deficiency
---------------------------------------------------
Mechanism Disorder------------------------------ - Decreased intake Nutritional deficiency
Impaired absorption
Celiac disease Tropcal sprue
Megaloblastic anemia due to Folate deficiency
---------------------------------------------------
Increased demand pregnancy Hemolytic anemia
Myeloprolifrative d . Leukemia & Lymphoma
Sidroblastic A Carcinoma
Inflamatory d Hyperthyroidsm
Skin diseases
Diagnosis of Mega a. due to Vit B12 deficiency
: Schilling test :Loading dose of parenteral Vit B12
and then given oral radioactive B12any absorbed B12 excreted in urine more
then 10% over the next 24 hours
The diagnosis of pernicious anemia is confirmed in the serum of autoantibodies to both
parietal cells in over 90% and Intrinsic factor in over 50% of paients
Deffrentiating Cbl , Folate and combined deficiency.
1-Cobalamin deficiency: Serum Cobalamin and red blood cell Folate level are low.
Serum folate level is normal.
2-Folate deficiency: Serum and red blood cell are normal.
Serum cobalamin is normal.
3-Combined cobalamin and folat deficiency all three test results are low.
Serum Homocysteine and Methylmalonic acid levels
-Reduced activity of methionin synthetase
-Ellevated serum levels of Homocysteine.
-Reduced conversion of MMCoA to succinyl CoA.
-Elevated levels of Methyl Malonyl Co A.
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
Treatment of Megaloblastic anemia
Hydroxycobalamin 5-10 ug/day im for two weeks
A brisk reticulocye response after one week
Followed by 1000 ug every three months
Folate deficiency is treated with oral Folic acid 5 mg /day for 15 days then followed by 1mg/day
Prophylactically in pregnancy,premature babiesdialysis, and chronic hemolysis
Folic acid should not given alone until B12 has been excluded to prevent precipitate neurological changes
