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

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

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

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

Vit.B 12 Plazma level of Vit. B ng/ L

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

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 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

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

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.

Normal cell Vs Megaloblastic cell

Blood film morphology Megaloblastic anemia Normal blood film

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 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 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 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