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  1. 1. Prepared by- Dr. Abdul Mottalib Sarker <ul><li>APPROACH TO </li></ul><ul><li>A PATIENT OF </li></ul><ul><li>ANEMIA </li></ul>
  2. 2. Definition <ul><li>Anemia may be defined as reduction of hemoglobin concentration per unit volume of blood below the lower limit of normal range for age & sex of the individual and clinically may be manifested by pale coloration in the skin & mucous membrane. </li></ul>
  3. 3. The normal range for Hb and RBC <ul><li>Hb RBC </li></ul><ul><li>Males 13-18g/dL (4.0-5.5)x 10 12 /L </li></ul><ul><li>Females 11.5-16.5g/dL (3.5-5.0)x 10 12 /L </li></ul><ul><li>Neonates 17-20g/dL (6.0-7.0)x 10 12 /L </li></ul>
  4. 4. Anemia classification <ul><li>Morphological classification </li></ul><ul><li>Pathophysiological classification </li></ul>
  5. 5. Morphological classification <ul><li>Type MCV fl MCH pg MCHC % </li></ul><ul><li>Macrocytic > 100 > 32 32-35 </li></ul><ul><li>Normocytic 80-100 27-32 32-35 </li></ul><ul><li>Microcytic < 80 < 27 < 32 </li></ul>
  6. 6. Anemia Check MCV MCV < 80 Microcytic anemia MCV 80 - 100 Normocytic anemia MCV > 100 Macrocytic anemia Defective synthesis of: Heme iron deficiency anemia anemia of chronic disease sideroblastic anemia lead poisoning Globin chains thalassemias HbE Fe
  7. 7. Pathophysiological classification <ul><li>Blod loss anemia </li></ul><ul><li>Increase rate of red cell destruction </li></ul><ul><li>Impaired red cell production </li></ul>
  8. 9. ERYTHROPOIESIS <ul><li>In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages </li></ul>Proerythroblast … Stem cell Early erythroblast Intermediate erythroblast Reticulocyte RBC
  9. 10. Normal Red Blood Cells
  10. 12. Normal Peripheral Smear
  11. 13. Iron Deficiency Anemia
  12. 14. Microcytic Hypochromic Anemia <ul><li>Iron deficiency Anemia </li></ul>
  13. 15. IRON DEFICIENCY ANEMIA Prevalence
  14. 16. IRON DEFICENCY - STAGES <ul><li>Prelatent </li></ul><ul><ul><li>reduction in iron stores without reduced serum iron levels </li></ul></ul><ul><ul><ul><li>Hb (N), MCV (N), iron absorption (  ), transferin saturation (N), serum ferritin (  ), marrow iron (  ) </li></ul></ul></ul><ul><li>Latent </li></ul><ul><ul><li>iron stores are exhausted, but the blood hemoglobin level remains normal </li></ul></ul><ul><ul><ul><li>Hb (N), MCV (N), TIBC (  ), serum ferritin (  ), transfe r rin saturation (  ), marrow iron (absent) </li></ul></ul></ul><ul><li>Iron deficiency anemia </li></ul><ul><ul><li>blood hemoglobin concentration falls below the lower limit of normal </li></ul></ul><ul><ul><ul><li>Hb (  ), MCV (  ), TIBC (  ), serum ferritin (  ), transfer r in saturation (  ), marrow iron (absent) </li></ul></ul></ul>
  15. 17. Iron metabolism <ul><li>Amount </li></ul><ul><li>Total body iron= 2-5 gm </li></ul><ul><li>Distribution </li></ul><ul><li>Hemoglobin – 2-3gm </li></ul><ul><li>Storage iron ( ferriin & hemosiderin ) -1gm </li></ul><ul><li>Essential (non available) tissue iron -0.5gm </li></ul><ul><li>Plasma or transport iron - 3-4 mgm </li></ul>
  16. 18. <ul><li>Transport protein – transferrin (beta globulin) One mol binds one or two atoms of ferric iron </li></ul><ul><li>normal value – 1.2 – 2 g/l </li></ul><ul><li>Serum iron </li></ul><ul><li>normal value – 100ug/dl </li></ul><ul><li>TIBC –It is the amount of transferrin available to bind with iron, normal value – 300ug/dl </li></ul><ul><li>TIBC is normally 3 times that of serum iron </li></ul>
  17. 19. IRON Body Compartments - 75 kg man 3 mg Absorption < 1 mg/day Excretion < 1 mg/day Stores 1000mg Tissue 500 mg Red Cells 2300 mg
  18. 20. IRON <ul><li>Functions as electron transporter; vital for life </li></ul><ul><li>Must be in ferrous (Fe +2 ) state for activity </li></ul><ul><li>In anaerobic conditions, easy to maintain ferrous state </li></ul><ul><li>Iron readily donates electrons to oxygen, superoxide radicals, H 2 O 2 , OH• radicals </li></ul><ul><li>Ferric (Fe +3 ) ions cannot transport electrons or O 2 </li></ul><ul><li>Organisms able to limit exposure to iron had major survival advantage </li></ul>
  19. 21. IRON CYCLE Fe Fe Fe Fe Fe Ferritin Hemosiderin slow Fe Fe Fe Fe Fe Fe Fe Fe Fe Ferritin Ferritin Transferrin Receptor RBC PRECURSOR CIRCULATING RBCs Fe Fe TRANSFERRIN MONONUCLEAR PHAGOCYTES
  20. 22. Iron absorption <ul><li>Duodenum </li></ul><ul><li>Proximal jejunum </li></ul><ul><li>Influenced by rate of erythropoiesis and state of iron stores. </li></ul>
  21. 24. Causes of Iron Deficiency <ul><li>Blood Loss </li></ul><ul><ul><li>Gastrointestinal Tract </li></ul></ul><ul><ul><li>Menstrual Blood Loss </li></ul></ul><ul><ul><li>Urinary Blood Loss (Rare) </li></ul></ul><ul><ul><li>Blood in Sputum (Rarer) </li></ul></ul><ul><li>Increased Iron Utilization </li></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Infancy </li></ul></ul><ul><ul><li>Adolescence </li></ul></ul><ul><ul><li>Polycythemia Vera </li></ul></ul><ul><li>Malabsorption </li></ul><ul><ul><li>Tropical Sprue </li></ul></ul><ul><ul><li>Gastrectomy </li></ul></ul><ul><ul><li>Chronic atrophic gastritis </li></ul></ul><ul><li>Dietary inadequacy (almost never sole cause) </li></ul><ul><li>Combinations of above </li></ul>
  22. 25. GENERAL SYMPTOMS <ul><li>GENERAL ANEMIA’S SYMPTOMS: </li></ul><ul><ul><ul><ul><li>FATIGABILITY </li></ul></ul></ul></ul><ul><ul><ul><ul><li>DIZZENES </li></ul></ul></ul></ul><ul><ul><ul><ul><li>HEADACHE </li></ul></ul></ul></ul><ul><ul><ul><ul><li>SCOTOMAS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>IRRITABILITY </li></ul></ul></ul></ul><ul><ul><ul><ul><li>ROARING </li></ul></ul></ul></ul><ul><ul><ul><ul><li>PALPITATION </li></ul></ul></ul></ul><ul><ul><ul><ul><li>CHD, CHF </li></ul></ul></ul></ul>
  23. 26. CHARACTERISTICS SYMPTOMS <ul><ul><ul><ul><li>GLOSSITIS, STOMATITIS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>DYSPHAGIA ( Plummer-Vinson syndrome ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>ATROPHIC GASTRITIS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>DRY, PALE SKIN </li></ul></ul></ul></ul><ul><ul><ul><ul><li>SPOON SHAPED NAILS, KOILONYCHIA, </li></ul></ul></ul></ul><ul><ul><ul><ul><li>BLUE SCLERAE </li></ul></ul></ul></ul><ul><ul><ul><ul><li>HAIR LOSS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS AN ICE, CLAY) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>SPLENOMEGALY (10%) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>INCREASED PLATELET COUNT </li></ul></ul></ul></ul>
  25. 29. Smooth tongue
  26. 32. Initial investigations of anaemia <ul><li>Full blood count </li></ul><ul><li>Examination of the blood film </li></ul><ul><li>Serum ferritin </li></ul><ul><li>Serum B12 </li></ul><ul><li>Red cell folate </li></ul><ul><li>Haemolysis screen (if indicated): reticulocyte count, serum bilirubin, serum lactate dehydrogenase, haptoglobins, urinary urobilinogen </li></ul>
  27. 33. Hematocrits Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera Plasma White cells Red cells
  28. 34. Second-line investigations of anaemia Direct antiglobulin test (DAT) - if DAT neg: G6PD screen, refer to haematologist Evidence of haemolysis Coeliac antibodies and/or duodenal biopsy - if small bowel malabsorption, refer to gastroenterologist Low red cell folate Gastric parietal cell antibodies (not specific), intrinsic factor antibody (specific for pernicious anaemia), Schilling test (B12 absorption test) Low serum B12 Oesophagogastroduodenoscopy (OGD), colonoscopy, gynaecological examination, coeliac antibodies (anti-tissue transglutaminase) Iron deficiency
  29. 35. Third-line investigations of anaemia Thyroid function tests, Liver function tests, Haemolysis screen (if not already performed) Macrocytic anaemias Renal function, Haemolysis screen (if not already performed), Immunoglobulins and paraprotein screen, Search for evidence of underlying infective, inflammatory or neoplastic disorder Normocytic anaemias Haemoglobin electrophoresis Search for evidence of underlying infective, inflammatory or neoplastic disorder (blood cultures, ESR, C-reactive protein, ANA, CXR etc.) Microcytic anaemias
  30. 36. N HB A 2 ,F increase N N HB electro Ring form present absent absent Blast iron present present Present Absent BM Iron I N N D Ferritin Normal Normal D I TIBC Inc Normal D D Serum Iron D D D decrease MCHC D D D “ MCH Decrease Decreas e Low/N decrease MCV Sidero Thal ACD Fe Def Investigation
  31. 37. BLOOD AND BONE MARROW SMEAR <ul><li>BLOOD: </li></ul><ul><ul><li>microcytosis, h y pochromia, anisocytosis poikilocytosis </li></ul></ul><ul><li>BONE MARROW </li></ul><ul><ul><li>high cellularity </li></ul></ul><ul><ul><li>mild to moderate erythroid hyperplasia ( 25-35%; N 16 – 18% ) </li></ul></ul><ul><ul><li>polychromatic and pyknotic cytoplasm of erythroblasts is vacuolated and irregular in outline ( micronormoblastic erythropoiesis ) </li></ul></ul><ul><ul><li>absence of stainable iron </li></ul></ul>
  32. 38. IDA bone marrow
  33. 39. Management <ul><li>History and physical examination is sufficient to exclude serious disease (e.g pregnant or lactating women, adolescents) </li></ul><ul><li>- CURE ANEMIA </li></ul>
  34. 40. <ul><li>History and/or physical examination is insufficient (e.g old men, postmenopausal women) </li></ul><ul><li>- FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT) </li></ul><ul><ul><ul><li>Benzidine test </li></ul></ul></ul><ul><ul><ul><li>Gastroscopy </li></ul></ul></ul><ul><ul><ul><li>Colonoscopy </li></ul></ul></ul><ul><ul><ul><li>Gynaecological examination </li></ul></ul></ul>
  35. 41. Treatment <ul><li>ORAL </li></ul><ul><ul><li>200 mg of iron daily 1 hour before meal (e.g. 100 mg twice daily) </li></ul></ul><ul><ul><li>Cont. </li></ul></ul><ul><ul><ul><li>14 days + (H b required level – H b current level) x 4 </li></ul></ul></ul><ul><ul><li>half of the dose 6 – 9 months to restore iron reserve </li></ul></ul><ul><ul><li>Absorption </li></ul></ul><ul><ul><ul><li>is enhanced: vit C, meat, orange juice, fish </li></ul></ul></ul><ul><ul><ul><li>is inhibited: cereals, tea, milk </li></ul></ul></ul>
  36. 42. <ul><li>PARENTERAL IRON SUBSTITUTION </li></ul><ul><ul><li>Bad oral iron tolerance (nausea, diarrhoea) </li></ul></ul><ul><ul><li>Necessity of quick management (CHD, CHF) </li></ul></ul><ul><ul><li>50 - 100 mg daily </li></ul></ul><ul><ul><li>I.v only in hospital (risk of anaph y lactic shock) </li></ul></ul><ul><ul><li>I.m in outpatient department </li></ul></ul><ul><ul><li>Total dose by iv infusion: </li></ul></ul><ul><ul><li>iron to be injected (mg) = (15 - Hb g ) x body weight (kg) x 3 </li></ul></ul>
  37. 43. CALCULATION OF RETICULOCYTE PRODUCTION INDEX <ul><li>Correction #1 for anemia : </li></ul>This correction produces the corrected reticulocyte count In a person whose reticulocyte count is 9%, hemoglobin 7.5 g/dL, hematocrit 23%, the absolute reticulocyte count = 9 × (7.5/15) [or × (23/45)]= 4.5% Correction #2 for longer life of prematurely released reticulocytes in the blood: This correction produces the reticulocyte production index In a person whose reticulocyte count is 9%, hemoglobin 7.5 gm/dL, hematocrit 23%, the reticulocyte production index (7.5/15)(hemoglobin correction) 2 (maturation time correction) = 9 × = 2.25
  38. 44. Failure of response to oral iron <ul><li>Lack of compliance </li></ul><ul><li>Continuing hemorrhage </li></ul><ul><li>Severe malabsorption </li></ul><ul><li>Another cause for the anemia </li></ul><ul><li>These possibilities should be considered before using parenteral iron </li></ul>
  39. 45. <ul><li>Iron deficiency anemia is a manifestation of an underlying process. Look for and treat the cause of the iron deficiency. </li></ul>
  40. 46. THANK YOU