MLAB 1415: H K B -M

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MLAB 1415: HEMATOLOGY
KERI BROPHY-MARTINEZ
Hemolytic 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


◦
Horizontal




Separating of lipid bilayer from skeletal lattice
Result in decrease in surface area-to-volume
ratio..spherocyte
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 SPHEROCYTOSIS
CLINICAL 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

Red cells are incubated at 37̊ C for 48 hours.
Degree of hemolysis is increased when spherocytes
are present.
 Red

test
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 ELLIPTOCYTOSIS
CLINICAL 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 PYROPOIKILOCYTOSIS
CLINICAL 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/1
3593250277/elliptocytes
 McKenzie, S. B. (2010). Clinical Laboratory
Hematology (2nd ed.). Upper Saddle River, NJ:
Pearson Education, Inc.
 http://tiny.cc/d59xy

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