Module 9 Normocytic Anemias Acquired and Hereditary Acknowledgments Ministry of Health Guyana Centers for Disease Control and Prevention CDC Global AIDS Program GAP Guyana Centers for Disease Control and Prevention CDC Atlanta American Society for Clinical Pathology ASCP Objectives Upon completion of this lesson the student will be able to Contrast the acquired hemolytic anemias due to extrinsic defects and the hereditary hemolytic anemias due to intrinsic defects Describe the blood picture of the normal newborn Evaluate the normocytic normochromic anemias due to marrow failure based on etiology clinical findings blood and bone marrow findings tests used to aid in diagnosis and treatment Marrow replacement anemia Aplastic anemia Acquired Congenital Fanconi s Objectives Evaluate the laboratory findings associated with the following normocytic normochromic hemolytic anemias due to extrinsic defects based on etiology clinical findings blood and bone marrow findings and tests used to aid in diagnosis and treatment Warm autoimmune hemolytic anemias WAIHA Cold autoimmune hemolytic anemias CAIHA Transfusion reaction Hemolytic disease of the newborn Rh ABO Anemias due to mechanical trauma Microangiopathic anemias DIC HUS March hemoglobinuria Anemias due to infectious agents Anemias due to heat other miscellaneous Objectives Explain compensated and uncompensated hemolytic disease Contrast intravascular and extravascular destruction of erythrocytes in hemolytic disorders Contrast the anemias of acute and chronic blood loss Contrast the hereditary hemolytic anemias due to intrinsic defects of the RBC and the acquired hemolytic anemias due to extrinsic defects Objectives Describe usual post splenectomy findings Describe the principle and diagnostic value of the erythrocyte osmotic fragility test Describe methods for inducing the sickling phenomenon Objectives Evaluate the findings associated with the following normocytic normochromic hemolytic anemias due to intrinsic defects based on etiology clinical findings blood and bone marrow findings and tests used to aid in diagnosis and treatment Hereditary spherocytosis Hereditary ovalocytosis elliptocytosis Hereditary acanthocytosis abetalipoproteinemia Hereditary stomatocytosis Hemoglobinopathies Hemoglobin S and C disorders G 6 PD deficiency Pyruvate kinase deficiency Terms Antigen Antibody Ig types Complement Terms C3 induced RBC lysis Phagocytosis Osmotic lysis Fragmentation Hemoglobin denaturation Classification of Anemia Normocytic Normochromic Anemias Due to increased RBC loss or decreased RBC production Majority are hemolytic caused by increased destruction Classification of hemolytic anemias Mode of transmission Type of defect Hereditary versus acquired Intrinsic the red cell is abnormal Extrinsic an external agent or trauma destroys red cell Site of destruction Extravascular or Intravascular Normocytic Normochromic Anemias Compensated hemolytic disease RBC replacement RBC destruction Anemia does not develop marrow production keeps up with loss Uncompensated hemolytic disease RBC destruction RBC replacement by marrow See anemia with high retic but too low to keep up with rate of RBC loss Hemolytic Anemia Normocytic Normochromic Hemolytic Anemias due to Extrinsic Defects Acquired hemolytic anemias Extrinsic defects due to antibodies trauma infectious agents heat drugs chemicals decrease lifespan Severity depends on rate of hemolysis and the degree of bone marrow compensatory response Increased retic count but loss production Characterized by abnormal RBC destruction tests and damaged rigid red cells Definitions for Immune Anemias Antigens and antibodies Antigen Ag on RBC membrane Antibody Ab in serum plasma 5 immunoglobulin types IgM cold room temp large can visually see IgG warm body temp small can t see need to do DAT DAT detects IgG antibody and or complement that has coated the red cell membrane in vivo Normally antibodies are not formed against antigens you possess Iso alloantibody is formed against a foreign non self antigen after exposure Autoantibody is produced against host self antigens Antigen Antibody Reactions Most Ag Ab reactions require complement End result of C3 Activation is lysis If RBC hemolysis Macrophages have IgG C3 receptors Warm and Cold Autoantibodies Spherocytes Agglutination Warm Autoimmune HA WAIHA Altered immune response causes production of an IgG autoantibody against self RBC antigens Antibody attaches to RBC antigen spherocytes Primary idiopathic or secondary to disease Spherocytes polychromasia Blood Warm Autoimmune HA WAIHA Lab findings Mod to severe anemia spherocytes high MCHC Erythrophagocytosis Looks similar to H spherocytosis but positive DAT Treatment Ingestion of coated RBC Blood RBC Monocyte with ingested RBC Electron Microscopy RBC Cold Autoimmune HA CAIHA Altered immune response causes production of an IgM autoantibody against self RBC antigens Antibody C3 attaches to RBC antigen agglutination Primary idiopathic or secondary to disease 50x 100x RBC Agglutination Cold Autoimmune HA CAIHA Few clinical problems unless IgM antibody titers are high 1 1000 Lab findings Symptoms of acrocyanosis Raynaud s phenomenon Severity varies with seasons avoid the cold IgM antibodies cause RBC agglutination Positive Direct Antiglobulin Test detects complement Problems obtaining valid RBC parameters Blood sample must be warmed prior to analysis Hemolytic Transfusion Reaction Incompatible blood transfusion Recipient has antibodies to antigens on the donor red cells received Donor cells are destroyed ABO worst Intravascular hemolysis that is complement induced lysis immediate Can be life threatening Normal Newborn Blood Picture High RBC count Hgb 20 g dL and HCT Macrocytic RBCs MCV 110 fL high retics Up to 10 NRBCs diff Blood NRBC Hemolytic Disease of the Newborn Caused by maternal IgG antibodies directed against baby RBC antigens HDN due to Rh incompatibility Antibodies cross placenta and destroy fetal red cells Rh negative mother forms Rh antibody after exposure HDN due to ABO incompatibility Mother s ABO blood type is O baby is type A or B B C A D Hemolytic Anemias due to Trauma Fragmentation syndromes most common finding on smear are schistocytes anemia varies Types of trauma Mechanical valves cardiac Microangiopathic MAHA small vessels DIC HUS March hemoglobinuria contact Schistocytes Fibrin Strands RBC RBC fragmentation on fibrin strands Hemolytic Anemias due to Infectious Agents Thermal Burns Anemia varies