1. ANEMIA Department of Clinical Microscopy Faculty of Associated Medical Sciences, Chiang Mai University PRASIT CHANARAT, M.S.(Clin.Path ) PC

2. ANEMIA Symptoms : Pallor Jaundice Fatique Palpitation Dyspnea Virtigo Peptic ulcer Glossitis Dysphagia etc PC

3. Classification of Anemia I. Etiologic Classification 1. Impaired RBC production 2. Excessive destruction 3. Blood loss II. Morphologic Classification 1. Macrocytic anemia 2. Microcytic hypochromic anemia 3. Normochromic normocytic anemia III. Kinetic Classification IV. Physiologic Classification PC

4. Impaired RBC Production 1. Abnormal bone marrow 1.1 Aplastic anemia 1.2 Myelophthisis : Myeloficrosis, Leukemia, Cancer metastasis 2. Essential factors deficiency 2.1 Deficiency anemia : Fe, Vit. B12, Folic acid, etc 2.2 Anemia in renal disease : Erythropoietin 3. Stimulation factor deficiency 3.1 Anemia in chronic disease 3.2 Anemia in hypopituitarism 3.3 Anemia in hypothyroidism PC

5. Excessive Destruction of RBC (cont.) Hemolytic anemia 1. Intracorpuscular defect 1.1 Membrane : Hereditary spherocytosis Hereditary ovalocytosis, etc. 1.2 Enzyme : G-6PD deficiency, PK def., etc. 1.3 Hemoglobin : Thalassemia, Hemoglobino- pathies PC

6. Excessive Destruction of RBC 2. Extracorpuscular defect 2.1 Mechanical : March hemolytic anemia MAHA (Microangiopathic HA) 2.2 Chemical/Physical 2.3 Infection : Clostridium tetani 2.4 Antibodies : HTR, SLE 2.5 Hypersplenism PC

7. Blood Loss 1. Acute blood loss : Accident, GI bleeding 2. Chronic blood loss : Hypermenorrhea Parasitic infestation PC

8. Macrocytic Anemia MCV > 94 MCHC > 31 1. Megaloblastic dyspoiesis 1.1 Vit. B12 deficiency : Pernicious anemia 1.2 Folic acid deficiency : Nutritional megaloblas- tic anemia, Sprue, Other malabsorption 1.3 Inborn errors of metabolism : Orotic aciduria, etc. 1.4 Abnormal DNA synthesis : Chemotherapy, Anticonvulsant, Oral contraceptives PC

9. Macrocytic Anemia MCV > 94 MCHC > 31 2. Non-Megaloblastic dyspoiesis 2.1 Increased erythropoiesis : Hemolytic anemia response to hemorrhage 2.2 Increased membrane surface area : Hepatic disease, Obstructive jaundice, Post- splenectomy 2.3 Idiopathic : Hypothyroidism, Hypoplastic and Aplastic anemia PC

10. Microcytic Hypochromic Anemia MCV < 80 MCHC < 31 1. Fe deficiency anemia : Chronic blood loss, Inadequate diet, Malabsorption, Increased demand, etc. 2. Abnormal globin synthesis : Thalassemia with or without Hemoglobinopathies 3. Abnormal porphyrin and heme synthesis : Pyridoxine responsive anemia, etc. 4. Other abnormal Fe metabolism : PC

11. Normocytic Normochromic Anemia MCV 82 - 92 MCHC > 30 1. Blood loss 2. Increased plasma volume : Pregnancy, Overhydration 3. Hemolytic anemia : depend on each cause 4. Hypoplastic marrow : Aplastic anemia, RBC aplasia 5. Infiltrate BM : Leukemia, Multiple myeloma, Myelofibrosis, etc. 6. Abnormal endocrine : Hypothyroidism, Adrenal insufficiency, etc. 7. Kidney disease / Liver disease / Cirrhosis PC

12. Kinetic Classification of Anemia 1. Insufficient erythropoiesis Stem cells , Hypoplastic marrow, Infiltrated BM 2. Ineffective erythropoiesis - Megaloblastic anemia - Thalassemia - Sideroblastic anemia 3. Uncompensated hemolytic disease with continued bleeding PC

13. Physiologic Classification of Anemia 1. RPI (Reticulocyte Production Index) < 2 (Ineffective erythropoiesis) 1.1 Hypoproliferative anemia 1.2 Maturation disorder 2. RPI > 3 (Effective erythropoiesis 2.1 Hemolytic anemia 2.2 Blood loss anemia PC

14. Physiologic Classification of Anemia 1. RPI (Reticulocyte Production Index) < 2 (Ineffective erythropoiesis) 1.1 Hypoproliferative anemia (normocytic normochromic, N/N) - Hypoplastic anemia - Idiopathic/ Chemical/ Infectious / Drug --> Maturation arrest - Myelophthisic anemia (Marrow infiltration) - Refractory anemia (Dysmyelopoietic syndrome) PC

15. 1.1.1 N/N and normal RDW a) BM failure b) Decrease marrow stimulation - Endocrine disease - Anemia of chronic disease - Renal disease 1.1.2 Abnormal RBC morphology & RDW a) Oval macrocyte :- Refractory dysmyelo- poietic b) Dacrocytes/ tear drops :- Myelophthisic PC Physiologic Class. of Anemia RPI < 2

16. 1.2 Maturation disorder 1.2.1 Microcytic, high RDW a) Siderblastic (Microcytic dimorphic RBC) b) Fe def. (Microcytic hypochromic RBC) 1.2.2 Microcytic, normal RDW a) Heterozygous, thalassemia syndrome b) Anemia of chronic disease 1.2.3 Macrocytic a) Liver disease b) Folate def. c) Vit. B12 def. d) Hemolytic anemia (Normocyte polychromasia) PC Physiologic Class. of Anemia RPI < 2

17. Physiologic Classification of Anemia 2. RPI > 3 (Effective erythropoiesis) 2.1 Hemolytic anemia - Intrinsic hereditary disorder - Extrinsic acquired disorder 2.2 Blood loss - Acute blood loss - Chronic blood loss (without treatment --> micro- cytic, hypochromic anemia) PC

18. Evaluation of Anemia A. Hematologic 1. Hematocrit (VPRC preferred) 2. Hemoglobin concentration 3. RBC indices : MCV, MCH, MCHC 4. Leukocyte count 5. Reticulocyte count 6. Platelet count 7. ESR (Erythrocyte sedimentation rate) 8. Stained blood smear : RBC morphology PC

19. Evaluation of Anemia B. Urine analysis 1. Appearance : Color, pH, Clarity, sp gr 2. Test for protein, Bence Jones protein 3. Bilirubin, Uribilinogen 4. Occult blood 5. Microscopic examination C. Stool 1. Appearance : Color, consistency 2. Occult blood 3. Examination for ova, parasites PC

20. Evaluation of Anemia D. Serum or Plasma 1. BUN 2. Creatinine, if urea N is abnormal 3. Bilirubin : Direct, indirect 4. Protein 5. SI (Serum iron), TIBC (Total iron binding capacity) E. Special tests in hematology Hb typing / Ham acid test / Coombs’ test, G-6PD, Ferritin, Sucrose test, Autohemolysis test, Haptoglobin, etc. PC

36. Koilonychia - Iron Deficiency

37. Hypochromic Microcytic Anemia (Iron Deficiency)

38. Vitamin B 12 Absorption Parietal cells - produce IF IF B 12 B 12 B 12 IF Stomach IF Ileum - IF receptors B 12 B 12

42. Macroovalocytes and Hypersegmented Neutrophil

46. Normal Erythroids (Left); Megaloblasts (Right)

54. Bone Marrow Storage Iron (Blue)

56. Markedly Hypocellular BM - Aplastic Anemia

59. Breast Cancer Replacing BM

60. ANEMIA PC The End