ANEMIA

Functions of erythrocytes Transport of respiratory gases Large surface area : volume ratio Flexible biconcave disc Haemoglobin for exchange of gases Capable of glycolysis for the source of energy for cell survival

Erythrocyte disorders Qualitative Haemoglobin defect (Anemia, Thalassaemia, sickle cell anemia etc) Membrane & enzyme abnormalities (G6PD, eliptocytosis, stomato-ovalocytosis) Quantitative Increased (polycythemia) inherited / acquired Decrease (inherited / acquired hypoplasia) Bleeding

Anaemia Reduction in circulation haemoglobin Nutritional deficiency anaemias –Iron deficiency –B12 & folate deficiency anaemia –Protein deficiency anaemia –Scurvy & other element deficiency Iron anaemia deficiency B12 & folate deficiency

Nutritional deficiency anaemia clinical application Angular Cheilosis Koilonychia Glossitis Marrow iron stores Plummer-Vinson syndrome

Anaemia; Globin chain defects Thalassaemias –Reduced globin chain synthesis Alpha and Beta chain synthesis defects Haemoglobinopathies –Abnormal globin chain synthesis Sickle cell disease Thalassaemia

Anaemia; Globin chain defects X-ray appearance of Thalassaemic patient Hemoglobin electrophoresis for the diagnosis of thalassaemai

Anaemia; Membrane and enzyme defects Membrane defects –Elliptocytosis –Hemolysis –Stomato-ovalocytosis –Without haemolysis Red cell enzymopathies G6PD –Hemolysis after oxidant stress Blood loss Elliptocytosis G6PD deficiency

Anaemia; Reduced erythroid bone marrow Marrow failure Marrow infiltration Trephine biopsy (Aplastic Anemia ) Marrow infiltration Normal trephine

C.B.C Haemoglobin - 15±2.5, 14 ±2.5 - g/dl PCV ±0.07, 0.42 ± l/l (%) –Haematocrit, effective RBC volume - better RBC count ±1, 4.8 ± 1 x1012/l MCHC - Hb/PCV g/dl –Hb synthesis within RBC MCH - Hb/RBC ± 2.5 pg/l –Average Hb in RBC MCV - PCV/RBC 85 ± 8 - fl

Microcytic Anemia (IDA)

Macrocytic Anemia (Meg.):

ANEMIA Symptoms : Pallor Jaundice Fatigue Palpitation Dyspnea Vertigo Peptic ulcer Glossitis Dysphagia etc

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

Impaired RBC Production 1. Abnormal bone marrow 1.1 Aplastic anemia 1.2 Myelophthisis : Myelofibrosis, 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

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

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

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

Macrocytic Anemia MCV > 94 MCHC > 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

Macrocytic Anemia MCV > 94 MCHC > 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

Microcytic Hypochromic Anemia MCV < 80 MCHC < 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 :

Normocytic Normochromic Anemia MCV MCHC > 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

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

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

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)

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

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

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)

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

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

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.