1. MEGALOBLASTIC ANEMIAS Nada Mohamed Ahmed, MD, MT (ASCP)i

2. Contents Definition Causes Function of B 12,folate General feature lab diagnosis

3. 3 MEGALOBLASTIC ANEMIAS Causes 1. Vit. B 12 deficiency 2. Folic acid deficiency

4. Functions of folate and vitamin B12 folat e and vitamin B12 are required for DNA synthesis and for maintenance of neurons and red blood cells.

5. 5 VITAMIN B 12 AND FOLIC ACID- PHYSIOLOGIC CONSIDERATIONS Vitamin B 12 Folic acid Sources meat, fish green vegetables, yeast Daily requirement 2-5 ug 50-100 ug Body stores 3-5 mg (liver) 10-12mg (liver) Places of absorption ileum duodenum and proxymal segment of small intestine

6. Vit.B 12 Plazma level of Vit. B 12 200 - 900 ng/ L

7. Folate levels: Normal ranges Serum:6 – 21  g/L (RBC volume) Red cell: 160 – 640  g/L (RBC volume) Folate deficiency Serum folate : <4  g /L Red cell folate: <140  g /L

8. 8 MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency(1) 1. Malabsorption a) Inadequate production of intrinsic factor - pernicious anemia - gastrectomy, partial or total b) Inadequate releasing vit. B 12 from food (partial gastrectomy, abnormality of stomach function, chronic pancreatic insufficiency) c) Terminal ileum disease (sprue, celiac disease, ilea resection, Crohn disease, Imerslund syndrome) d) Competition for intestinal B 12 : - bacterial overgrowth: jejunal diverticula, intestinal stasis and obstruction due to strictures, blind-loop syndrome - Fish tapeworm

9. 9 MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency(2) 2. Inadequate intake - vegetarians 3. Inadequate utylisation Drugs: PAS, Neomycin, Colchicin, Nitrous oxide

10. 10 MEGALOBLASTIC ANEMIAS- Causes of Folic acid deficiency 1. Inadequate intake - diet lacking fresh, slightly cook food; chronic alcoholism, total parenteral nutrition, 2. Malabsorption - small bowel disease (sprue, celiac disease,) - alcoholism 3. Increased requirements: - pregnancy and lactation - infancy - chronic hemolysis - malignancy - hemodialysis 4. Defective utilisation Drugs:folate antagonists(methotrexate, trimethoprim, triamteren), purine analogs (azathioprine), primidine analogs (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin, N 2 )

11. 3-Glossitis : Sore tongue, poor taste sensation, pain Papill. atrophy-beefy tongue

12. 12 MEGALOBLASTIC ANEMIAS clinical features 1. Symptoms of anemia 2. Symptoms associated with vit. B 12 or Folic acid deficiency neurologic manifestations (exclusivly in wit. B 12 deficiency) - megaloblastic madness or psychosis, gastrointestinal compraints (vit.B 12 and folic acid deficiency) - loss of appetite - glosstis (red, sore, smooth tongue) - diarrhea or constipation

13. 13 MEGALOBLASTIC ANEMIAS Diagnosis(1) 1. Blood cell count: macrocytic anemia ( MCV>100fl ) thrombocytopenia leucopenia (granulocytopenia) low reticulocyte count 2. Blood smear: macroovalocytosis, anisocytosis, poikilocytosis hypersegmentation of neutrophyles

14. 14 VIT B 12 DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. Clinical symptoms of vit. B 12 deficiency 3. Low serum vit. B 12

15. 15 FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. History: causes of folate deficiency 3. Absence neurologic symptoms 4. Low serum and red blood cell folic acid

16. 16 MEGALOBLASTIC ANEMIAS TREATMENT(1) 1. Vitamin B 12 administration intramuscular in dose 1000 (100) μg per day for a week, then 100 μg 2x per week for 2 weeks, 1 x per week 100μg for month 2. Reticulocytosis begins 2 or 3 days after therapy started and maximal number reached on day 5 to 8., Vitamin B 12

17. 17 MEGALOBLASTIC ANEMIAS TREATMENT(2) FOLIC ACID DEFICIENCY ANEMIA 1. Oral administration of Ac. folicum 1 (5) mg per day, for 3 months, and maintance therapy if it’s necessary. 2. Reticulocytosis after 5-7 days