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  1. 1. Anemia Overview Ruozhi Xiao The Third Hospital of Sun Yat-sen University [email_address]
  2. 2. Erythrocytes parameters <ul><ul><li>RBC = red blood cells </li></ul></ul><ul><ul><li>Hgb= hemoglobin </li></ul></ul><ul><ul><li>Mean corpuscular volume (MCV) </li></ul></ul><ul><ul><ul><ul><li>N: 80-100 fl </li></ul></ul></ul></ul><ul><ul><li>RDW(Red cell Distr i bution Width) </li></ul></ul><ul><ul><li>Mean corpuscular hemoglobin (MCH) </li></ul></ul><ul><ul><ul><ul><li>N: 27-34 pg </li></ul></ul></ul></ul><ul><ul><li>Mean corpuscular hemoglobin concentration (MCHC) </li></ul></ul><ul><ul><ul><ul><li>N: 310 – 370 g/lRBC (31-37 g/dl) </li></ul></ul></ul></ul>
  3. 3. Survival and Production of RBC <ul><li>Formed in bone marrow </li></ul><ul><li>Life span is 120 days (+/-20 days) </li></ul><ul><li>Cleared in spleen </li></ul><ul><li>Reticulocytes are newly formed RBC in circulation </li></ul><ul><li>If no new production, Hgb drops 1 gm/week </li></ul>
  4. 5. ERYTHROPOIESIS In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages Proerythroblast RBC * -blast is the common suffix for an immature form of a cell Early erythroblast Intermediate erythroblast Late erythroblast Reticulocyte … … … … Stem cell
  5. 6. Hematocrits Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera Plasma White cells Red cells
  6. 7. Definitinon <ul><li>“ Low blood” </li></ul><ul><li>Anemia is simply a hemoglobin level lower than the normal range for a particular age and sex of the patient. </li></ul><ul><li>Most common hematologic disorder by far </li></ul>
  7. 8. The normal range for Hb and RBC <ul><li>Hb RBC </li></ul><ul><li>Males : 120 - 160g/L (4.0-5.5)x 10 12 /L </li></ul><ul><li>Females : 110 - 150g/L (3.5-5.0)x 10 12 /L </li></ul><ul><li>Neonates : 170 - 200g/L (6.0-7.0)x 10 12 /L </li></ul>
  8. 9. Anemia classification <ul><li>Based on general mechanisms </li></ul><ul><li>morphological classification </li></ul>
  9. 10. Anemia morphological classification <ul><li>Microcytic </li></ul><ul><li>Normocytic </li></ul><ul><li>Macrocytic </li></ul>
  10. 11. morphological classification Type MCV fl MCH pg MCHC % Macrocytic anemia > 100 > 32 32-35 Normocytic anemia 80-100 27-32 32-35 Microcytic anemia < 80 < 27 < 32
  11. 12. Normal Red Blood Cells - Peripheral Blood Smear
  12. 13. Normal Red Blood Cells
  13. 15. Microcytic anemia
  14. 16. Thalassemia <ul><li>Thalassa = the sea </li></ul><ul><li>Defective globin synthesis </li></ul><ul><ul><li>Normal  1  </li></ul></ul><ul><ul><li> thalassemia </li></ul></ul>
  15. 17. b-Thalassemia
  16. 19. Macrocytic anemia
  17. 20. General mechanisms of anemia <ul><li>1. RBC Loss without RBC destruction </li></ul><ul><li>2. Deficient RBC production: Marrow failure </li></ul><ul><li>3. Increased RBC destruction over production: Hemolysis </li></ul>
  18. 21. ANEMIA Causes - Cytoplasmic Protein Production <ul><li>Decreased hemoglobin synthesis </li></ul><ul><ul><li>Disorders of globin synthesis </li></ul></ul><ul><ul><li>Disorders of heme synthesis </li></ul></ul><ul><li>Heme synthesis </li></ul><ul><ul><li>Decreased Iron </li></ul></ul><ul><ul><li>Iron not in utilizable form </li></ul></ul><ul><ul><li>Decreased heme synthesis </li></ul></ul>
  19. 22. Pathophysiology <ul><li>Decreased RBC production </li></ul><ul><li>Iron deficiency </li></ul><ul><li>Folic acid deficiency </li></ul><ul><li>Aplastic anemia </li></ul><ul><li>Increased RBC loss or destruction </li></ul><ul><li>sickle cell anemia </li></ul><ul><li>blood loss </li></ul><ul><li>infection </li></ul>
  20. 23. The third hospital of Sun yat-sen university :Leukemia : trauma,surgery : cancer and ulcer,menstrual periods :Renal disease : Malaria :Lead poisoning : SLE <ul><ul><ul><li>:PNH </li></ul></ul></ul>
  21. 24. Bone Marrow Disorders <ul><li>Aplastic anemia </li></ul><ul><li>Myelodysplastic Syndromes </li></ul><ul><li>Acute Leukemia </li></ul>
  22. 25. Aplastic Anemia Blood Bone Marrow Biopsy
  23. 26. Bone Marrow (BM) Biopsy Normal Aplastic
  24. 27. Definitions <ul><li>Aplastic Anemia (AA) </li></ul><ul><ul><li>Pancytopenia </li></ul></ul><ul><ul><li>Hypocellular bone marrow </li></ul></ul><ul><li>Myelodysplastic Syndrome (MDS) </li></ul><ul><ul><li>Cytopenias with hypercellular bone marrow </li></ul></ul><ul><li>Acute Leukemia (AL) </li></ul><ul><ul><li>Malignant proliferation of immature cells </li></ul></ul>
  25. 28. Aplastic Anemia: Signs and Symptoms <ul><li>Anemia (low Hb, Hct) </li></ul><ul><ul><li>fatigue, lassitude, dyspnea </li></ul></ul><ul><li>Thrombocytopenia (low platelets) </li></ul><ul><ul><li>bruises, petechiae </li></ul></ul><ul><ul><li>serious bleeding </li></ul></ul><ul><li>Neutropenia (low neutrophils, a type of white cell) </li></ul><ul><ul><li>infections </li></ul></ul>
  26. 29. Acquired Aplastic Anemia <ul><li>Drugs </li></ul><ul><li>Chemicals </li></ul><ul><li>Viruses </li></ul><ul><li>Immune diseases </li></ul><ul><li>Paroxysmal nocturnal hemoglobinuria (PNH) </li></ul><ul><li>Pregnancy </li></ul><ul><li>IDIOPATHIC </li></ul>
  27. 30. Myelodysplastic Syndromes (MDS) <ul><li>Clonal diseases </li></ul><ul><li>Neoplastic </li></ul><ul><li>Refractory anemias </li></ul><ul><li>Potential for acute myeloid leukemia (AML) </li></ul>
  28. 31. 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
  29. 32. Clinical features <ul><li>Mild:Mild dyspnea on exertion, palpitation </li></ul><ul><li>Moderate: As with MILD ANEMIA, may also have excessive dyspnea </li></ul><ul><li>Severe:Anemia:Dyspnea at rest, tachycardia with pounding pulse, weakness, dizziness, headache, insomnia </li></ul>
  30. 33. Diagnosis of Anemia <ul><li>History </li></ul><ul><li>–Diet </li></ul><ul><li>–Blood loss </li></ul><ul><li>–Family history </li></ul><ul><li>–Recent illness or immunization </li></ul><ul><li>–History of anemia and cause </li></ul>
  31. 34. Diagnosis of Anemia <ul><li>Physical Examination </li></ul><ul><li>– Evaluate conjunctiva and mucous membranes for paleness </li></ul><ul><li>– Cardiovascular system for murmur </li></ul><ul><li>– Liver </li></ul><ul><li>– Spleen </li></ul><ul><li>– Nodes </li></ul><ul><li>– Look for jaundice or purpura </li></ul>
  32. 35. Diagnosis of Anemia <ul><li>Labs </li></ul><ul><li>– Complete blood count with differential and platelets </li></ul><ul><li>– Evaluation of smear with red cell indices </li></ul><ul><li>– Reticulocyte count </li></ul>
  33. 36. Diagnosis of Anemia <ul><li>Other tests </li></ul><ul><li>– Serum bilirubin, LDH, urinary hemosiderin, hgb electrophoresis, quantitative hgbA2 and F </li></ul>
  34. 37. Common treatment to All “Anemias” <ul><li>Support </li></ul><ul><ul><li>Hematopoietic growth factors </li></ul></ul><ul><ul><li>Blood transfusions, blood substitutes </li></ul></ul><ul><ul><li>Iron </li></ul></ul><ul><li>Cure </li></ul><ul><ul><li>Stem cell transplant </li></ul></ul><ul><ul><li>Gene therapy </li></ul></ul>
  36. 39. Terms <ul><li>Fe = iron </li></ul><ul><li>TIBC = total iron binding capacity </li></ul><ul><li>RDW = red cell distribution width </li></ul>
  37. 40. CASE 1 <ul><li>A 50 year old man comes to see you because of fatigue and a change in bowel habit. He is found to have a hemoglobin of 105 g/L (normal 120-170) and MCV of 78 fL (80-100). Peripheral blood film shows microcytes and hypochromia. He previously had a hemoglobin of 165 g/L three years ago, with a normal MCV. </li></ul>
  38. 41. Case 1 – Question 1 <ul><li>What is your approach to the history and physical examination? </li></ul>
  39. 42. Case 1 - Question 1 Discussion <ul><li>iron deficiency most likely </li></ul><ul><li>symptoms suspicious for lower GI tract malignancy. </li></ul><ul><li>still ask about chronic inflammatory diseases </li></ul><ul><li>ask about melena, hematochezia, weight loss, family history of colon ca </li></ul><ul><li>rectal exam indicated </li></ul>
  40. 43. CASE 1 - Question 2 <ul><li>What other investigations are appropriate? </li></ul>
  41. 44. Investigations <ul><li>serum ferritin 12 ug/L (30-400) </li></ul><ul><li>iron 8 umol/L (10-28) </li></ul><ul><li>TIBC 80 umol/L (38-76) </li></ul><ul><li>transferrin sat. 10 % (20-55) </li></ul><ul><li>Conclusion: Iron deficiency anemia </li></ul>
  42. 45. IRON DEFICIENCY ANEMIA Prevalence
  43. 46. 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>Ferric (Fe +3 ) ions cannot transport electrons or O 2 </li></ul>
  44. 47. IRON DEFICIENCY ANEMIA <ul><li>IRON METABOLISM </li></ul><ul><ul><li>ABSORPTION IN DUODENUM </li></ul></ul><ul><ul><li>TRANSFERRIN TRANSPORTS IRON TO THE CELLS </li></ul></ul><ul><ul><li>FERRITIN AND HEMOS I DERIN STORE IRON </li></ul></ul><ul><li>10% of daily iron is absorbed </li></ul>
  45. 48. Iron Metabolism <ul><li>Heme Iron </li></ul><ul><ul><li>Hemoglobin and myoglobin </li></ul></ul><ul><li>Non-heme Iron </li></ul><ul><ul><li>Breast milk </li></ul></ul><ul><ul><li>Cow milk </li></ul></ul><ul><ul><li>All supplements </li></ul></ul>
  46. 49. Iron Absorption <ul><li>Heme Iron </li></ul><ul><ul><li>Well absorbed </li></ul></ul><ul><ul><li>Not dependent on Iron deficiency status </li></ul></ul><ul><ul><li>Not limited by diet </li></ul></ul>
  47. 50. Iron Absorption <ul><li>Non-heme Iron </li></ul><ul><ul><li>Absorption is sporadic, generally poor </li></ul></ul><ul><ul><li>Improved absorption </li></ul></ul><ul><ul><ul><li>Iron deficient status </li></ul></ul></ul><ul><ul><ul><li>Heme iron (ie red meat, fish, chicken) </li></ul></ul></ul><ul><ul><ul><li>Vitamin C </li></ul></ul></ul><ul><ul><li>Worsened absorption </li></ul></ul><ul><ul><ul><li>Cow’s milk, cheese </li></ul></ul></ul><ul><ul><ul><li>Cereal </li></ul></ul></ul><ul><ul><ul><li>Tea </li></ul></ul></ul>
  48. 51. 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
  49. 52. Iron deficiency anemia <ul><li>Causes: </li></ul><ul><li>inadequate dietary iron intake </li></ul><ul><li>Malabsorption: gastrectomy, chronic diarrhea, </li></ul><ul><li>increased iron needs: pregnancy and lactation </li></ul><ul><li>chronic occult blood loss: bleeding ulcers, GI inflammation, hemorrhoids, cancer, chronic hemoglobinuria </li></ul><ul><li>Menstrual blood loss </li></ul>
  50. 53. <ul><li>Most body iron is present in hemoglobin in circulating red cells </li></ul><ul><li>The macrophages of the reticuloendothelial system store iron released from hemoglobin as ferritin and hemosiderin </li></ul><ul><li>S mall loss of iron each day in urine, faeces , skin and nails and in menstrua ting females as blood (1-2 mg daily) </li></ul>
  51. 54. IRON DEFICIENCY ANEMIA <ul><li>ETIOLOGY: </li></ul><ul><ul><ul><li>CHRONIC BLEEDING </li></ul></ul></ul><ul><ul><ul><ul><ul><li>MENORRHAGIA </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>PEPTIC ULCER </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>STOMACH CANCER </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>ULCERATIVE COLITIS </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>INTESTINAL CANCER </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>HAEMORRHOIDS </li></ul></ul></ul></ul></ul><ul><ul><ul><li>DECREASED IRON INTAKE </li></ul></ul></ul><ul><ul><ul><li>INCREASED IRON REQUIRMENT (JUVENILE AGE, PREGNANCY, LACTATION) </li></ul></ul></ul>
  52. 55. 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>
  53. 56. IRON DEFICIENCY ANEMIA <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 S </li></ul></ul></ul></ul><ul><ul><ul><ul><li>HEADACHE </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>
  54. 57. 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>
  55. 58. KOILONYCHIA <ul><li>  </li></ul> 
  56. 59. Smooth tongue
  57. 60. IRON DEFICIENCY ANEMIA <ul><li>MCV </li></ul><ul><li>MCH </li></ul><ul><li>MCHC N </li></ul><ul><li>Fe </li></ul><ul><li>TIBC </li></ul><ul><li>TRANSFERIN SATURATION </li></ul><ul><li>FERRITIN </li></ul>
  59. 62. BLOOD AND BONE MARROW SMEAR <ul><li>BLOOD: </li></ul><ul><ul><li>microcytosis, hipochromia, 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>
  60. 63. Anemia: Lab Evaluation <ul><li>Normal Periperhal Smear </li></ul><ul><li>Iron Deficiency Anemia </li></ul>
  61. 64. IDA blood smear
  62. 65. IDA bone marrow
  63. 66. Normal store iron(blue)
  64. 67. IDA
  65. 68. Reticulocytes up
  66. 69. Using special stains such as methylene blue or brilliant cresyl blue, reticulocytes stain with dark blue granules whereas mature erythrocytes evenly stain pale blue.
  67. 70. 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>
  68. 71. Management <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>
  69. 72. IRON DEFICIENCY ANEMIA CURE <ul><li>ORAL </li></ul><ul><ul><li>3 00 mg of iron daily after meal </li></ul></ul><ul><ul><li>How long? 3-6 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: tea, milk </li></ul></ul></ul>
  70. 73. IRON DEFICIENCY ANEMIA CURE <ul><li>PARENTERAL IRON SUBSTITUTION </li></ul><ul><ul><li>Bad oral iron tolerance (nausea, diarrhoea) </li></ul></ul><ul><ul><li>Negative oral iron absorption test </li></ul></ul><ul><ul><li>Necessity of quick management (CHD, CHF) </li></ul></ul>
  71. 74. Remember: Iron deficiency anemia is a manifestation of an underlying process. Look for and treat the cause of the iron deficiency.
  72. 75. Look for the cause <ul><li>colonoscopy reveals colon carcinoma which is subsequently resected. </li></ul>
  73. 76. Iron Deficiency anemia <ul><li>Diagnostics: </li></ul><ul><li>Iron levels </li></ul><ul><li>Total iron-binding capacity (TIBC) </li></ul><ul><li>Serum Ferritin </li></ul><ul><li>Medications: </li></ul><ul><li>Iron supplements, oral or parenteral </li></ul><ul><li>Vit. C </li></ul>
  74. 77. The End