1. 1 MEGALOBLASTIC ANEMIA M. Kaźmierczak XI 2012

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

3. 3 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

4. 4 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

5. 5 MEGALOBLASTIC ANEMIAS Causes of Vit.B 12 deficiency(2) 2. Inadequate intake - vegetarians 3. Inadequate utylisation Drugs: PAS, Neomycin, Colchicin, Nitrous oxide

6. 6 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 )

7. 7 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, - subacute, combined degeneration of the spinal cord ( proprioceptive and vibratory sensation, spinal ataxia) gastrointestinal compraints (vit.B 12 and folic acid deficiency) - loss of appetite - glosstis (red, sore, smooth tongue) - diarrhea or constipation

8. 8 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 granulocytes

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10. 10 MEGALOBLASTIC ANEMIAS Diagnosis(2) 3. Laboratory features indirect hyperbilirubinemia elevation of lactate dehrogenase (LDH) serum iron concentration- normal or increased 4. Bone marrow smear hypercellular increased erythroid /myeloid ratio erythroid cell changes (megaloblasts, RBC precursor a abnormally large with nuclear- cytoplasmic asynchrony) myeloid cell changes (giant bands and metamyelocytes, hypersegmentation) megakariocytes are decreased and show abnormal morphology

11. 11 Megaloblastic erythropoiesis

12. 12 MEGALOBLASTIC ANEMIAS Diagnosis 1. Diagnosis megaloblastic anemia 2. Establishing a type of deficiency (vit. B 12 and/or folic acid) 3. Establishing a cause of deficiency

13. 13 VIT B 12 DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. Clinical symptoms of vit. B 12 deficiency 3. Low serum vit. B 12 4. Increased concentration of methylmalonic acid (MMA) and total homocysteine

14. 14 PERNICIOUS ANEMIA DIAGNOSIS 1. Establishing vit.B 12 deficiency anemia 2. Absence of hydrogen ion secretion (achlorhydria) with maximal histamine stimulation 3. Radiolabeled vit. B 12 absorption test (Schilling urinary excretion test) : very reduced absorption of the B 12 -isotope, corrected to normal only when coadministered with a source of gastric IF. 4. Intrinsic factor, parietal cell and IF-vit.B 12 complex antibodies 5. Chronic atrophic gastritis

15. 15 Atrophic glossitis

16. 16 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 5. Normal concentration of methylmalonic acid (MMA) and increased of total homocysteine

17. 17 MEGALOBLASTIC ANEMIAS TREATMENT(1) PERNICIOUS ANEMIA 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. Serum iron monitoring, after 7-10 days of vit.B12 treatment, if Fe deficiency is diagnosed we should start iron substitution 3. 100 ug vit.B 12 i.m. every month, regimen that must be mainted for the rest on the patients life. 4. Oral substitution of cobalamin at doses 1000-2000ug/d

18. 18 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 3. Correction of anemia is over after 1-2 months therapy 4. Maintenance therapy if necessary