Module 8 Microcytic Hypochromic and Macrocytic Anemias 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 1 Evaluate the laboratory findings associated with microcytic hypochromic anemias based on etiology clinical findings blood and bone marrow findings and tests used to aid in diagnosis and treatment Iron deficiency anemia Sideroblastic anemias primary and secondary types Anemia of chronic disease Alpha and beta thalassemias major and minor types Objectives 2 Evaluate the macrocytic anemias based on etiology clinical findings blood and bone marrow findings and tests used to aid in diagnosis and treatment Megaloblastic anemia Vitamin B12 deficiency including Pernicious anemia Folate deficiency Non Megaloblastic anemia Liver disease Accelerated erythropoiesis Microcytic Hypochromic Anemias Characterized by impaired hemoglobin synthesis Normoblastic RBC maturation normocytic red cells Abbott Manual RBC maturation in microcytic anemias Lab Investigation of Anemia Iron Deficiency Anemia IDA Lack of iron results in reduced red blood cell hemoglobin production Causes Nutritional lack Malabsorption Increased need Chronic blood loss Sequence of iron depletion Storeage 1st Serum Iron depletion 2nd cell morphology 3rd Iron stored in liver transferrin transports iron Iron Deficiency Blood smear Blood findings ovalocyte Mild to severe microcytic hypochromic anemia Ovalocytes Pencil cells no RBC inclusions Pappenheimer Bodies Low serum iron high TIBC low serum ferritin Clinical symptoms Amount incorporated in the liver Decrease in amount of iron bound to transferrin in circulation Iron Deficiency Ovalocytes Pencil forms No RBC inclusions Bone marrow Wright s stained blood smear Treatment Identify cause Oral iron retic response No stainable iron Prussian blue iron stain 10x Sideroblastic Anemia SA Block s in protoporphyrin synthesis leads to iron overload and microcytic hypochromic anemia Sideroblastic Anemia SA Blood Pappenheimer bodies RBC with iron Wright s stain Bone marrow Sideroblast NRBC with iron Prussian blue stain Bone marrow Ringed Sideroblast NRBC with ring of iron Prussian blue stain 11 Sideroblastic Anemia SA Blood Pappenheimer bodies Wright s stain Blood findings Variable micro anemia RBC inclusions High serum iron low TIBC high serum ferritin Blood Basophilic stippling stippled RBCs Pappenheimer bodies Prussian blue iron stain Bloo d Sideroblastic Anemia SA Bone marrow Ringed Sideroblasts Prussian blue iron stain 100x Bone marrow Increased stainable iron Prussian blue iron stain 10x Types of Sideroblastic Anemia SA Blocks in the synthesis of protoporphyrin may be primary irreversible idiopathic cause unknown or secondary reversible can identify cause Secondary Types of SA Alcohol inhibits vitamin B6 pyridoxine Anti tuberculosis drugs inhibit vitamin B6 Lead causes multiple blocks Inhaled or ingested Abnormal lead level Neurologic problems Lead line gums Chelation therapy Stippled RBCs Lead poisoning Wright s stained blood smear Anemia of Chronic Disease ACD Anemia of chronic disease ACD inability to use iron and decreased response to EPO Associated conditions Persistent infection HIV chronic inflammatory or collagen disorders RA SLE malignant disease Blood findings Complex etiology history important Microcytic or normocytic severity parallels disease Very common anemia 2 Low serum iron low TIBC normal or high serum ferritin Treat underlying disorder if possible Iron harmful EPO may help Thalassemias Inherited decrease in alpha or beta globin chain synthesis needed for Hgb A quantitative defect All have microcytic hypochromic RBCs and target cells Genetic mutations classified by beta chains beta thalassemia Greek Italian alpha chains alpha thalassemia Asian Beta Alpha Target cells Codocytes 17 Thalassemias Normal globin chain production is balanced Severity ranges from lethal to severe transfusiondependency to no clinical abnormalities Major types severe no alpha or no beta chains made Minor trait types mild slight in normal hgb types May be a carrier Thalassemias Impaired alpha or beta globin synthesis results in an unbalanced number of chains produced that leads to RBC destruction in beta thalassemia major Production of compensatory hgb types in beta thals Formation of unstable or non functional hgb types in alpha thals Beta Thal Major Homozygous Both beta genes abnormal Marked decrease absence of beta chains leads to alpha chain excess no Hgb A is produced Rigid RBCs with Heinz bodies destroyed in bone marrow and blood ineffective erythropoiesis Heinz bodies Excess alpha chains Supravital stain Beta Thal Major Homozygous Clinical findings Lab findings Severe anemia target cells nucleated red cells RBC inclusions No hemoglobin A compensatory Hgb F Target cell HJB NRBC Stippled NRBC Wright s stained blood smear Beta BloodThal smear Major Homozygous HowellJolly body NRBC Pap bodies Target cell Target cells Transfused RBC Blood smear Transfused RBC Treatment Transfusion Splenectomy Iron chelation Hypercellular Bone Marrow 10x Beta Thal Minor Heterozygous One abnormal beta gene Slight decreased rate of beta chain production Blood picture can look similar to iron deficiency Stippled RBC Lab findings Mild anemia target cells no nucRBCs stippled RBCs No Heinz bodies Normal iron tests Compensates with Hgb A2 Target cell Ovalocytes Wright s stained blood smear Alpha Thal Major Homozygous Deletion of all 4 alpha genes results in complete absence of alpha chain production No normal hemoglobin types made Known as Barts Hydrops Fetalis Die of hypoxia Bart s hgb Alpha Thal Intermedia Hgb H Disease Three alpha genes deleted Moderate decrease in alpha chains leads to beta chain excess unstable Hgb H Moderate anemia Heinz bodies Excess beta chains Supravital stain Target cells Wright s stain blood smear Alpha Thal Minor Heterozygous One or two alpha genes deleted group Slight decrease in alpha chain production Mild or no anemia few target cells Essentially normal electrophoresis many undiagnosed Beta Thalassemias Alpha Thalassemias Differential Diagnosis of Microcytic Anemia HGB Synthesis Defects Macrocytic Anemias Characterized by elevated MCV MCH values normal MCHC Includes Megaloblastic and non Megaloblastic anemia Wright s stained blood smear Lab