MLAB 1415: Hematology Keri Brophy-Martinez Chapter 15: Hemolytic Anemia: Membrane Defects

Introduction Defects due to abnormalities in membrane proteins or lipids Defects alter membrane’s stability, shape, deformability and permeability Hemolysis occurs extravascularly

Overview: Membrane Defects Skeletal protein abnormalities Vertical Separating of lipid bilayer from skeletal lattice Result in decrease in surface area-to-volume ratio..spherocyte Horizontal Disruption of skeletal lattice Membrane destabilizes Cell fragmentation..poik Lipid composition abnormalities Excess cholesterol accumulates in the outer bilayer of the RBC Acanthocyte

Conditions Associated with Membrane Defects Hereditary spherocytosis Hereditary elliptocytocytosis Hereditary pyropoikilocytosis Overhydrated and dehydrated hereditary stomatocytosis Membrane lipid disorders Paroxysymal noctural hemoglobinuria

Disorders Hereditary spherocytosis (HS) Defect in ankyrin & spectrin Results in the formation of fragile spherocytic red cells. Spherocyte becomes less flexible and more permeable to Na+ Tends to affect Northern Europeans Inherited

Clinical Findings Varies in severity Compensated hemolytic disease No anemia Intermittent jaundice Splenomegaly Cholelithiasis: pigment bile stones from increased bilirubin breakdown

Lab Features CBC RBC morphology Mild anemia MCV is usually normal (77-87fL) MCH normal MCHC is >36% (This is the only condition in which an MCHC can be truly increased.) RBC morphology Spherocyte Varying degrees of polychromasia, anisocytosis and poikilocytosis

Lab Features Bone Marrow Normoblastic erythroid hyperplasia Increased iron storage Chemistry Increased Bilirubin Fecal urobilinogen LD Decreased Haptoglobin Immunohematology DAT negative

Diagnostic tests for HS Osmotic fragility - ↑ Cells are incubated in decreasing concentrations of NaCl. Spherocytes lyse sooner than normal red cells. Autohemolysis test Red cells are incubated at 37̊ C for 48 hours. Degree of hemolysis is increased when spherocytes are present. Red cell membrane studies Membrane proteins are analyzed using gel electrophoresis.

Treatment of HS Splenectomy Corrects for the anemia, but the membrane defect remains

Disorders Hereditary elliptocytosis A defect of one of the skeletal proteins Results in the formation of fragile elliptocytic red cells that are sensitive to mechanical stress. More permeable to Na+ Tends to affect blacks, especially in Africa

Clinical findings Hemolysis not evident Anemia not characteristic

Lab Features CBC RBC morphology Mild anemia Hgb level increased Elliptocytes or ovalocytes

Treatment of HE Treatment is usually not necessary, but if patients have hemolysis, splenectomy is beneficial.

Disorders Hereditary pyropoikilocytosis (HPP) Severe subtype of HE Deficiency of α-spectrin and a mutant spectrin leads to disruption of skeletal lattice and cell destabilization Cells fragment when heated Tends to affect blacks Presents in infancy or early childhood

Clinical Findings Hyperbilirubinemia

Lab Features CBC RBC morphology MCV decreased (25-55 fL) Extreme erythrocyte morphologies Fragments, elliptocytes, triangulocytes etc

Treatment of HPP Splenectomy

Disorders Hereditary Stomatocytosis Syndromes No treatment required Overhydrated Hereditary Stomatocytosis (OHS) Permeable to Na+ and K+, cell takes on water Cells resemble stomatocytes Dehydrated Hereditary Stomatocytosis (DHS) Water content decreased causing cell dehydration so cells look like targets No treatment required

Lab Features Anemia is mild to moderate Increased bilirubin MCV increased Stomatocytes: OHS Target cells: DHS

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. http://tiny.cc/d59xy