MLAB 1415-Hematology Keri Brophy-Martinez Chapter 14: Introduction to Hemolytic Anemias

Hemolytic anemia Anemia caused by hemolysis of red blood cells – Hemolysis is the destruction of erythrocytes resulting in the release of hemoglobin Results in reduction of normal red cell lifespan. Normocytic, normochromic anemia RBC’s are prematurely destroyed

Classified by… Source of defect causing the hemolysis – Intrinsic/extrinsic Poikilocyte present – Schistocytes/Spherocytes Mode of onset – Inherited/acquired Location of hemolysis – Intravascular/Extravascular

Lab Features Reticulocytosis – RPI> 2 Erythroid hyperplasia of bone marrow M:E ratio decreased Peripheral blood – Normochromic,normocytic – Polychromasia – nRBCs Tests for heme catabolism abnormal – Unconjugated/conjugated bilirubin – Haptoglobin

Lab Features Increased Bone Marrow Production of Erythrocytes Increased Erythrocyte Destruction Reticulocytosis (RPI>2)Anemia LeukocytosisSpherocytes, Schistocytes, Poikilocytes nRBCs in PBDecreased haptoglobin PolychromasiaIncreased bilirubin Normoblastic erythroid hyperplasia in bone marrow Increased LDH M:E decreasedIncreased urobilinogen Increased expired CO Hemoglobinemia* Hemoglobinuria* Hemosiderinuria* *Only with intravascular hemolysis

Diagnostic Approach to Hemolytic Anemias Increased RBC Production Increased RBC Destruction COOMBS (DAT) test Immune Hemolytic Anemias P eripheral blood smear RBC Morphology Lab Investigation Definitive Diagnosis

Clinical Findings Jaundice Pallor Fatigue Cardiac symptoms Gallstones Dark or red urine Splenomegaly

Sites of Destruction Intravascular – Hemolysis occurs within the circulation – RBC’s are severely damaged Extravascular – Hemolysis occurs within the macrophages of the spleen, liver or bone marrow – More common than intravascular

Intravascular Destruction 1.RBC is hemolyzed 2.Free hgb released into plasma 3.Hgb binds to haptoglobin – If haptoglobin depleted, hemopexin can step in 4.This complex goes to liver 5.Complex converted to bilirubin 6.Bilirubin excreted to intestinal tract

Terms 1.Hemoglobinemia – Occurs if hemopexin and haptoglobin is depleted. Free hgb circulates in blood. 2.Hemoglobinuria – Occurs if free hgb can not be absorbed by the liver and kidney 3. Hemosiderinuria Hemosiderin in the urine, sign of filtration of hemoglobin thru the kidney

Causes of Intravascular Hemolysis Activation of Complement on RBC Membrane Physical or Mechanical Trauma to the RBC Toxic Microenvironment of the RBC Paroxysmal noctural hemoglobinuria Microangiopathic hemolytic anemia Bacterial infections Paroxysmal cold hemoglobinuria Abnormalities of heart vessels Plasmodium falciparum infection Some transfusion reactionsDisseminated intravascular coagulation Venoms Some autoimmune hemolytic anemias Thermal injury Acute drug reaction in G6PD deficiency

Extravascular Destruction 1.Hgb is degraded within the phagocyte to heme and globin a.Phagocyte locations: Spleen: removes slightly damaged RBCs Liver: removes severely damaged RBCs Bone marrow: remove mature precursor cells that are intrinsically abnormal 2.Heme further degraded to iron, biliverdin and carbon monoxide 3.Biliverdin enters plasma as bilirubin 4.Bilirubin binds to albumin, excreted by the liver

Causes of Extravascular Hemolysis OriginAnemias Inherited RBC DefectsThalassemia, Hemoglobinopathies, Enzyme deficiencies, Membrane disorder Acquired RBC DefectsMegaloblastic anemia, Vitamin E deficiency in newborns Immunohemolytic anemiasAutoimmune, Drug induced, Some transfusion reactions

Source of Defect of RBC Intrinsic – Abnormality of the RBC Membrane Cell enzymes Hemoglobin molecule – Usually hereditary EXCEPTION: Acquired – Paroxysymal noctural hemoglobinuria (PNH) – Site of hemolysis: extravascular

Source of Defect of RBC Extrinsic – Antagonist in cell’s environment causes injury to the RBC Antagonistic plasma factors Traumatic physical cell injury Immune mediated cell destruction – RBC is normal – Usually acquired – Site of hemolysis: intra or extravascular

Referenes Harmening, D. M. (2009). Clinical Hematology and Fundamentals of hemostasis (5th ed.). Philadelphia, PA: F.A. Davis Company. McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc..