1. IRON DEFICIENCY ANEMIA M. Kaźmierczak XI2012

2. ANEMIA - DEFINITION  REDUCTION OF HEMOGLOBIN CONCENTRATION BELOW REFERENCE VALUE

3. BLOOD PARAMETERS  Hemoglobin concentration (Hg) F: 7,2 –10; M: 7,8-11,3 mmol Fe/l (12-18 g/dl)  Erythrocytes count (RBC) F: 4-5,5; M: 4,5-6 x10 12 /l ( 4-6 x10 6 /  l)  Hematocrit (Hct) F: 37-47; M: 40-54; (37-54%)  Platelet count (Plt) 150 – 450 x 10 3 /  l (150-450 x 10 9 /l)  Leukocytes count (WBC) 4-10 x 10 9 /l (4-10 x 10 3 /  l)

4. Erythrocytes parameters –Mean corpuscular volume (MCV) –N: 80-100 fl –RDW(Red cell Distrubution Width) –Mean corpuscular hemoglobin (MCH) –N: 27-34 pg –Mean corpuscular hemoglobin concentration (MCHC) –N: 310 – 370 g/lRBC (31-37 g/dl)

5. Reticulocytes  RET: 0,5-2%  ARC (absolute reticulocyte count ): 25-75x 10 9 /l  CRC (corrected reticulocyte count)  RPI (reticulocyte production index)

6. IRON METABOLISM  Iron concentration (Fe) N: 50-150  g/dl  Total Iron Binding Capacity N: 250-450  g/dl  Transferrin saturation  Transferrin receptor concentration  Ferritin concentration N: 50-300  g/l

7. IRON DEFICIENCY ANEMIA  IRON METABOLISM –ABSORPTION IN DUODENUM –TRANSFERRIN TRANSPORTS IRON TO THE CELLS –FERRITIN AND HEMOSYDERIN STORE IRON  10% of daily iron is absorbed

8.  Most body iron is present in hemoglobin in circulating red cells  The macrophages of the reticuloendotelial system store iron released from hemoglobin as ferritin and hemosiderin  Small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily)

10. IRON DEFICIENCY - STAGES  Prelatent –reduction in iron stores without reduced serum iron levels Hb (N), MCV (N), iron absorption (  ), transferin saturation (N), serum ferritin (  ), marrow iron (  )  Latent –iron stores are exhausted, but the blood hemoglobin level remains normal Hb (N), MCV (N), TIBC (  ), serum ferritin (  ), transferrin saturation (  ), marrow iron (absent)  Iron deficiency anemia –blood hemoglobin concentration falls below the lower limit of normal Hb (  ), MCV (  ), TIBC (  ), serum ferritin (  ), transferrin saturation (  ), marrow iron (absent)

11. Laboratory tests in iron deficiency of increasing severity NormalIron deficiency without anemia Iron deficiency with mild anemia Severe iron deficiency with severe anemia Marrow reticulo- endothelial iron2+ to 3+None Serum iron (SI), µg/dL60 to 150 <60<40 Total iron binding capacity (transferrin, TIBC), µg/dL 300 to 360300 to 390350 to 400>410 Transferrin saturation (SI/TIBC), percent 20 to 5030<15<10 Hemoglobin, g/dLNormal 9 to 126 to 7 Red cell morphologyNormal Normal or slight hypochromia Hypochromia and microcytosis Plasma or serum ferritin, ng/mL40 to 200<40<20<10 Erythrocyte protoporphyrin, ng/mL RBC 30 to 70 >100100 to 200 Other tissue changesNone Nail and epithelial changes Laboratory tests in iron deficiency of increasing severity

12. IRON DEFICIENCY ANEMIA  ETIOLOGY: BLOOD LOSS Chronic bleeding MENORRHAGIA PEPTIC ULCER STOMACH CANCER ULCERATIVE COLITIS INTESTINAL CANCER HAEMORRHOIDS Intravascular hemolysis Pulmonary hemosiderosis Response to erythropoietin DECREASED IRON INTAKE INCREASED IRON REQUIRMENT (JUVENILE AGE, PREGNANCY, LACTATION) CONGENITAL IRON DEFICIENCY

13. IRON DEFICIENCY ANEMIA  GENERAL ANEMIA’S SYMPTOMS: –FATIGABILITY –DIZZINESS –HEADACHE –SCOTOMAS –IRRITABILITY –ROARING –PALPITATION –CHD, CHF

14. CHARACTERISTIC SYMPTOMS –GLOSSITIS, STOMATITIS –DYSPHAGIA ( Plummer-Vinson syndrome) –ATROPHIC GASTRITIS –DRY, PALE SKIN –SPOON SHAPED NAILS, KOILONYCHIA, –BLUE SCLERAE –HAIR LOSS –PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS ICE, CLAY) –SPLENOMEGALY (10%) –INCREASED PLATELET COUNT

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16. IRON DEFICIENCY ANEMIA  MCV  MCH  MCHC N  Fe TIBC and sTfR  TRANSFERIN SATURATION  FERRITIN

17. BLOOD AND BONE MARROW SMEAR  BLOOD: –microcytosis, hipochromia, anulocytes, anisocytosis poikilocytosis  BONE MARROW –high cellularity –mild to moderate erythroid hyperplasia (25-35%; N 16 – 18%) –polychromatic and pyknotic cytoplasm of erythroblasts is vacuolated and irregular in outline (micronormoblastic erythropoiesis) –absence of stainable iron

19. Management  History and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents) - CURE ANEMIA  History and/or physical examination is insufficient (e.g old men, postmenopausal women) - FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT) Benzidine test Gastroscopy Colonoscopy Gynaecological examination

20. ORAL IRON ABSORPTION TEST 1. baseline serum iron level 2. 200 - 400 mg of elemental iron orally 3. serum iron level 1-4 hours after ingestion An increase in serum iron of at least 100 microg/dL indicates that oral iron absorption is generally adequate

21. IRON DEFICIENCY ANEMIA CURE  ORAL –200 mg of iron daily 1 hour before meal (e.g. 100 mg twice daily) –How long? 14 days + (Hg required level – Hg current level) x 4 –half of the dose - 6 – 9 months to restore iron reserve

22. Factors influencing the absorption of dietary iron Absorption of heme iron Amount of heme iron, especially in meat Content of calcium in the meal (calcium impairs iron absorption) Absorption of nonheme iron Iron status Amount of potentially available nonheme iron Balance between positive and negative factors Positive factors Ascorbic acid Meat or fish (heme iron enhances absorption of nonheme iron) Negative factors Phytate (in bran, oats, rye fiber) Polyphenols (in tea, some vegetables and cereals) Dietary calcium Soy protein

23. IRON DEFICIENCY ANEMIA CURE  PARENTERAL IRON SUBSTITUTION –Bad oral iron tolerance (nausea, diarrhoea) –Negative oral iron absorption test –Necessity of quick management (CHD, CHF) –iron to be injected (mg) = (15 - Hb/g%/) x body weight (kg) x 3 –IM or IV ? (risk of anaphilactic reactions) Intramuscular iron — Mobilization of iron from intramuscular (IM) sites is slow and occasionally incomplete. As a result, the rise in the hemoglobin concentration is only slightly faster than that which occurs following the use of oral iron preparations. Ferric carboxymaltose — is a novel stable iron complex for intravenous (IV) use which can be given at single doses of up to 1000 mg of elemental iron per week over a recommended infusion time of 15 minutes. A number of trials have shown efficacy and safety of this agent in iron deficient patients.

24. SIDEROBLASTIC ANEMIAS  HEREDITARY DISORDERS (rare)  SYNONIM FOR MDS (RA,RAES)  DISTURBANCES IN INTRACELLULAR IRON METABOLISM  HIGHER SIDEROBLASTS NUMBER IN BONE MARROW  CORRECT OR HIGHER IRON CONCENTRATION