MEGALOBLASTIC ANEMIAS 1 MEGALOBLASTIC ANEMIAS Causes 1 Vit

MEGALOBLASTIC ANEMIAS 1

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

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

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 4

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

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) 6

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 7

MEGALOBLASTIC ANEMIAS Diagnosis(1) 1. Blood cell count: • • macrocytic anemia ( MCV>100 fl ) thrombocytopenia leucopenia (granulocytopenia) low reticulocyte count 2. Blood smear: • • macroovalocytosis , anisocytosis, poikilocytosis hypersegmentation of granulocytes 8

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 , hypertsegmentation) • megakariocytes are decreased and show abnormal morphology 9

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 10

VIT B 12 DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. Clinical symptoms of vit. B 12 deficiency 3. Low serum vit. B 12 11

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 12

FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS 1. Establishing megaloblastic anemia 2. History: causes of folate deficiency okoliczności sprzyjające niedoborowi kw. foliowego 3. Absence neurologic symptoms 4. Low serum and red blood cell folic acid 13

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 2 x 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. B 12 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 14 on the patients life.

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 15 4. Leczenie podtrzymujące w zależności od przyczyny