MLAB 1415: HEMATOLOGYKERI BROPHY-MARTINEZHemolytic Anemia: Membrane Defects

Part One

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

HEREDITARY SPHEROCYTOSISCLINICAL FINDINGS

Varies in severity Compensated hemolytic disease Anemia- varies with severity Intermittent jaundice Splenomegaly Cholelithiasis: pigment bile stones from

increased bilirubin breakdown

HEREDITARY SPHEROCYTOSIS LAB FEATURES

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

HEREDITARY SPHEROCYTOSIS LAB FEATURES Bone Marrow

Normoblastic erythroid hyperplasia Increased iron storage

Chemistry Increased

Bilirubin Fecal urobilinogen LD/LDH

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 37A 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+

Increased sensitivity to heat Found commonly in Africa and the Mediterranean

HEREDITARY ELLIPTOCYTOSISCLINICAL FINDINGS

Hemolysis not evident Anemia not characteristic

HEREDITARY ELLIPTOCYTOSIS LAB FEATURES

CBC Mild anemia Hgb level increased

RBC morphology Elliptocytes or

ovalocytes

TREATMENT OF HE

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

Condition is not fatal

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

HEREDITARY PYROPOIKILOCYTOSISCLINICAL FINDINGS

Hyperbilirubinemia

HEREDITARY PYROPOIKILOCYTOSIS LAB FEATURES

CBC MCV decreased (25-55 fL)

RBC morphology Extreme erythrocyte morphologies

Fragments, elliptocytes, triangulocytes etc

TREATMENT OF HPP

Splenectomy

DISORDERS

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

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.

http://laboratorysciencereview.tumblr.com/post/13593250277/elliptocytes

McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc.

http://tiny.cc/d59xy