MLAB 1415: Hematology Keri Brophy-Martinez

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MLAB 1415 HematologyKeri Brophy-Martinez

• Chapter 15
• Hemolytic Anemia Membrane Defects

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Introduction

• Defects due to abnormalities in membrane proteins
  or lipids
• Defects alter membranes stability, shape,
  deformability and permeability
• Hemolysis occurs extravascularly

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OverviewMembrane 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

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Conditions Associated with Membrane Defects

• Hereditary spherocytosis
• Hereditary elliptocytocytosis
• Hereditary pyropoikilocytosis
• Overhydrated and dehydrated hereditary
  stomatocytosis
• Membrane lipid disorders
• Paroxysymal noctural hemoglobinuria

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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

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Clinical Findings

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

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Lab Features

• CBC
• Mild anemia
• MCV is usually normal (77-87fL)
• MCH normal
• MCHC is gt36 (This is the only condition in
  which an MCHC can be truly increased.)
• RBC morphology
• Spherocyte
• Varying degrees of polychromasia, anisocytosis
  and poikilocytosis

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Lab Features

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

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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 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.

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Treatment of HS

• Splenectomy
• Corrects for the anemia, but the membrane defect
  remains

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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

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Clinical findings

• Hemolysis not evident
• Anemia not characteristic

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Lab Features

• CBC
• Mild anemia
• Hgb level increased
• RBC morphology
• Elliptocytes or ovalocytes

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Treatment of HE

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

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Disorders

• Hereditary pyropoikilocytosis (HPP)
• Severe subtype of HE
• Deficiency of a-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

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Clinical Findings

• Hyperbilirubinemia

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Lab Features

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

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Treatment of HPP

• Splenectomy

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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

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Lab Features

• Anemia is mild to moderate
• Increased bilirubin
• MCV increased
• Stomatocytes OHS
• Target cells DHS

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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