MLAB 1315Hematology Keri BrophyMartinez

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MLAB 1315-HematologyKeri Brophy-Martinez

• Unit 12 Introduction to Hemolytic Anemias

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Hemolytic anemia

• Anemia caused by hemolysis of red blood cells,
  due to the trapping of cells in the sinuses or
  spleen or liver.
• Results in reduction of normal red cell
  lifespan.
• Normocytic, normochromic anemia
• RBCs are prematurely destroyed

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Two categories of hemolytic anemia

• Intracorpuscular
• Intrinsic defect of the red cell
• Hereditary
• Defects of the red cell membrane
• Enzyme defects
• Hemoglobinopathies
• Thalassemia syndromes
• Acquired
• Paroxysmal nocturnal hemoglobinuria (PNH)

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• Extracorpuscular
• Extrinsic abnormality
• Immune hemolytic anemias
• Infections
• Chemical agents and toxins
• Physical agents
• Microangiopathic and macroangiopathic hemolytic
  anemias
• Splenic sequestration (hypersplenism)
• General systemic disorders (without dominant
  hemolysis)

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Laboratory tests for hemolysis

• Increased red cell destruction
• Indirect bilirubin
• Serum haptoglobin
• Increased red cell production
• Retic
• Corrected retic
• Reticulocyte production index

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Red cell membrane defects

• Hereditary spherocytosis
• A loss of surface area of the red cell membrane
  protein (such as spectrin) and membrance protein
  dysfunction result in the formation of fragile
  spherocytic red cells.
• CBC
• Mild anemia
• MCV is usually normal
• MCHC is gt36 (This is the only condition in
  which an MCHC can be truly increased..)

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• RBC morphology
• Spherocyte - a smaller than normal RBC with
  concentrated hemoglobin content and no central
  pallor
• Varying degrees of polychromasia, anisocytosis
  and poikilocytosis

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Diagnostic tests

• Osmotic fragility - ?
• Cells are incubated in decreasing concentrations
  of saline. 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

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

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• Hereditary elliptocytosis
• A defect in the horizontal interactions of the
  red cell membrane skeleton results in the
  formation of elliptocytic red cells that are
  sensitive to mechanical stress.
• CBC usually normal but mild anemia may exist in
  some patients
• Peripheral smear - marked increase in
  elliptocytes or ovalocytes.
• Treatment is usually not necessary, but if
  patients have hemolysis, splenectomy is
  beneficial.

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HEREDITARY ENZYME DEFICIENCIES

• Glucose-6-Phosphate Dehydrogenase Deficiency
  (G6PD)
• G6PD deficiency is a hereditary sex-linked anemia
  in which denatured hemoglobin precipitates in the
  RBC after exposure to oxidative stress causing
  hemolysis.
• G6PD is the primary enzyme in the hexose
  monophosphate shunt aerobic glycolytic pathway.

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• G6PD activity is highest in young red cells (see
  note). Oxidative stress can cause hemolysis.
• Causes of oxidative stress are as follows
• Ingestion of oxidative drugs such as primaquine
  for malaria can cause hemolysis in 10 of
  American black males. This was first noticed
  during the building of the Panama Canal.
• Ingestion of fava beans and oxidative drugs such
  as quinine and quinidine can cause hemolysis in
  non-blacks. Favism is found in the Mediterranean
  area.

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• Precipitates of denatured hemoglobin in the red
  cell are called Heinz bodies (cannot be seen on
  Wrights stain, only a supravital stain) Red
  cells with these precipitates cannot deform to
  pass through microcirculation and they hemolyze

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Laboratory tests for G6PD deficiency

• ? HH (hemoglobin and hematocrit)
• Hemoglobinuria
• Heinz bodies in the red cells
• Bilirubin and haptoglobin
• Note G6PD deficiency during an acute hemolytic
  episode may be difficult to detect since the
  presence of increased retics which contain more
  G6PD may mask the deficiency in the mature red
  cells.

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• Pyruvate kinase deficiency
• Pyruvate kinase deficiency is an autosomal
  recessive anemia in which red cells are unable to
  retain water which results in hemolysis, due to
  cell shrinkage, distortion of shape and increased
  membrane rigidity
• Pyruvate kinase is an essential enzyme in the
  Embden-Meyerhof pathway

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Laboratory tests

• HH - slight? to marked ?
• Peripheral smear - severity of anemia dictates
  degree of reticulocytosis, polychromasia, aniso,
  poik and NRBCs.
• Definitive test is PK enzyme assay.
• Fluorescent screening test

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Methemoglobin reductase deficiency

• The function of the MR pathway is to prevent
  oxidation of heme. If the amino acid sequence is
  abnormal in the hemoglobin molecule, heme iron is
  reduced to methemoglobin (Fe3) and oxygen
  transport is affected. The major clinical sign
  is cyanosis (bluish skin), since methemoglobin
  can not carry O2 to the tissues.
• Usually a benign condition