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