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

2. Definition of Megaloblastic Anemia Causes Function of B 12,folate. General feature lab diagnosis Objectives

3. Definition of Megaloblastic Anemia It is a Macrocytic Hypochromic Anemia which characterized by Impaired DNA formation due to lack of: B12 or folate in ultimately active form.

4. 4 MEGALOBLASTIC ANEMIAS 1. Vit. B 12 deficiency 2. Folic acid deficiency Causes

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

6. 6 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

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

8. 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

9. 9 MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency 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 d) Competition for intestinal B 12 : - bacterial overgrowth: jejunal diverticula, intestinal stasis and obstruction due to strictures, blind-loop syndrome - Fish tapeworm

10. 10 MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency 2. Inadequate intake - vegetarians 3. Inadequate utylisation Drugs: PAS, Neomycin, Colchicin, Nitrous oxide

11. 11 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 )

12. 12 Symptoms of Megaloblastic Anemias 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. 3-Glossitis : Sore tongue, poor taste sensation, pain Papill. atrophy-beefy tongue

14. 14 MEGALOBLASTIC ANEMIAS Diagnosis 1. Complet Blood count (CBC) macrocytic anemia ( MCV>100fl ) thrombocytopenia leucopenia (granulocytopenia) low reticulocyte count 2. Blood smear: macroovalocytosis, anisocytosis, poikilocytosis hypersegmentation of neutrophyles.

15. Normal cell Vs Megaloblastic cell

16. Blood film morphology Megaloblastic anemia Normal blood film

17. 17 VIT B 12 DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. Clinical symptoms of vit. B 12 deficiency 3. Low serum vit. B 12

18. 18 DIAGNOSIS 1. Establishing megaloblastic anemia 2. History: causes of folate deficiency 3. Absence neurologic symptoms 4. Low serum and red blood cell folic acid FOLIC ACID DEFICIENCY ANEMIA

19. 19 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

20. 20 Megaloblastic anemias treatment 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