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MLAB 1415: H EMATOLOGY K ERI B ROPHY -M ARTINEZ Hemolytic Anemia: Membrane Defects Part One.

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Presentation on theme: "MLAB 1415: H EMATOLOGY K ERI B ROPHY -M ARTINEZ Hemolytic Anemia: Membrane Defects Part One."— Presentation transcript:

1 MLAB 1415: H EMATOLOGY K ERI B ROPHY -M ARTINEZ Hemolytic Anemia: Membrane Defects Part One

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

3 O VERVIEW : M EMBRANE D EFECTS  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

4 C ONDITIONS A SSOCIATED WITH M EMBRANE D EFECTS ◦ Hereditary spherocytosis ◦ Hereditary elliptocytocytosis ◦ Hereditary pyropoikilocytosis ◦ Overhydrated and dehydrated hereditary stomatocytosis ◦ Membrane lipid disorders ◦ Paroxysymal noctural hemoglobinuria

5 D ISORDERS  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

6 H EREDITARY S PHEROCYTOSIS C LINICAL F INDINGS Varies in severity Compensated hemolytic disease Anemia- varies with severity Intermittent jaundice Splenomegaly Cholelithiasis: pigment bile stones from increased bilirubin breakdown

7 H EREDITARY S PHEROCYTOSIS L AB F EATURES CBC 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. ) RDW Increased RBC morphology Spherocyte Varying degrees of polychromasia, anisocytosis and poikilocytosis

8 H EREDITARY S PHEROCYTOSIS L AB F EATURES Bone Marrow Normoblastic erythroid hyperplasia Increased iron storage Chemistry Increased Bilirubin Fecal urobilinogen LD/LDH Decreased Haptoglobin Immunohematology DAT negative

9 D IAGNOSTIC 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 37 ̊ C for 48 hours. Degree of hemolysis is increased when spherocytes are present. Red cell membrane studies Membrane proteins are analyzed using gel electrophoresis.

10 T REATMENT OF HS Splenectomy Corrects for the anemia, but the membrane defect remains

11 D ISORDERS 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 + Increased sensitivity to heat Found commonly in Africa and the Mediterranean

12 H EREDITARY ELLIPTOCYTOSIS C LINICAL FINDINGS Hemolysis not evident Anemia not characteristic

13 H EREDITARY ELLIPTOCYTOSIS L AB F EATURES CBC Mild anemia Hgb level increased RBC morphology Elliptocytes or ovalocytes

14 T REATMENT OF HE Treatment is usually not necessary, but if patients have hemolysis, splenectomy is beneficial. Condition is not fatal

15 D ISORDERS 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


17 H EREDITARY P YROPOIKILOCYTOSIS L AB F EATURES CBC MCV decreased (25-55 fL) RBC morphology Extreme erythrocyte morphologies Fragments, elliptocytes, triangulocytes etc

18 T REATMENT OF HPP Splenectomy

19 D ISORDERS Hereditary Stomatocytosis Syndromes 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

20 L AB F EATURES Anemia is mild to moderate Increased bilirubin MCV increased Stomatocytes: OHS Target cells: DHS

21 R EFERENES Harmening, D. M. (2009). Clinical Hematology and Fundamentals of hemostasis (5th ed.). Philadelphia, PA: F.A. Davis Company. 3593250277/elliptocytes McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc.

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