Week 2: Hemolytic Anemia Normocytic anemia Fanconi anemia Diamond-Blackfan (PRCA) Types of hemolysis Evidence of hemolysis Reticulocyte G6PD deficiency Heinz bodies PK deficiency Cytoskeleton Spherocytosis Elliptocytosis PNH Normocytic Anemia Acute hemorrhage Hypo-proliferative Acquired aplastic anemia Constitutional aplastic anemia Pure red cell aplasia (PRCA) Acute Hemorrhage No changes in CBC until plasma volume increases Later, reticulocytosis Hypoproliferative Anemia Pancytopenia < 25% BM cellularity Low retic count Bone marrow defect Immunologic suppression Growth Factor deficiency Abnormal stem cells Acquired Aplastic Anemia Idiopathic Drugs and chemicals (eg, chloramphenicol, benzene, insecticides) Radiation Virus Paroxysmal nocturnal hemoglobinuria Constitutional Aplastic Anemia Fanconi’s anemia Chromosomal breaks Pure Red Cell Aplasia PRCA Infections Drugs Diamond-Blackfan syndrome No EPO deficiency Hemolytic Anemia Intravascular vs extravascular Bilirubin metabolism Types Membrane defect Metabolic defect Extracorpuscular Evidence of Hemolysis Low RBC survival with chromium tagging study Unconjugated bilirubin Plasma Hb Decreased serum haptoglobin Evidence of Erythropoiesis Polychromasia Increased reticulocyte “Shift” macrocytosis Hypercelluar BM Correcting Retic Count Retic Index = Retic % x Patient Hct Normal Hct Absolute Retic = Retic % x RBC/mm3 Retic Production Index = Retic Index Days in circulation Membrane Defect Spherocytosis Elliptocytosis PNH (sensitivity to complement lysis -sugar water test, Ham’s test) Stomatocytosis (possibly Rh null) Spherocytes Elliptocytes Osmotic Fragility Paroxysmal Nocturnal Hemoglobinuria Hematopoietic stem cell disorder Mutation of phosphatidylinositol glycan class A (PIG-A) gene Glycosylphosphatidylinositol (GPI) anchors membrane proteins Without GPI, unable to regulate completment activities on membrane Hemolysis is pH dependent Thrombosis can occur Lab Tests for PNH Acidified serum lysis test (Ham’s test): PNH cells lyse due to complement activation in acidified serm Sugar water (sucrose hemolysis) test: RBCs sensitive to complement will lyse in sucrose and serum Flow cytometry: lack of CD59 on RBCs, or lack of CD59 or CD55 on granulocytes Stomatocytes Metabolic Defect G6PD deficiency Hexose monophosphate shunt Most common RBC enzyme defect, >50 variants X-linked Low glutathione due to low NADPH Oxidative lysis, Heinz bodies, spherocytic Primaquine, fava beans Pyruvate kinase deficiency Glycolysis Low RBC ATP level Non-spherocytic B12 and folate deficiency Macrocytic HJ bodies Hemoglobinopathies Poikilocytosis Abnormal Hb Heinz body preparation with Crystal violet Unstable hemoglobin Extracorpuscular Factors Antibodies Autoimmune Isoimmune Drugs, antibiotics Fresh water Abnormal plasma lipids Acanthocytosis Venom Snake Spider Bee Extracorpuscular Factors Trauma DIC Hemolytic uremic syndrome (HUS) TTP Angiopathy Heat Heart valves “March” hemoglobinuira Microorganisms Malaria Babesia Clostridium Gram negative endotoxin Schistocytes Malaria