Acquired haemolytic anaemias

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Acquired haemolytic anaemias

• Waggas Ahmed Elaas

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• Acquired Haemolytic anaemias are usually the
  result of an'extracorpuscular' or 'environmental'
  change.
• The defect comes from out side the red cells.
• They are classified generally into
• Immune Haemolytic anaemias
• Non immune Haemolytic anaemias

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Classification

• Acquired Haemolytic anaemias A. Immune
  hemolytic anemias 1. Autoimmune hemolytic
  anemia - caused by warm-reactive
  antibodies - caused by cold-reactive
  antibodies 2. Alloimmune hemolytic anemia
  -caused by hemolytic transfusion reaction
  - caused by hemolytic disease of newborn
  (HDN) 3. Drug associatedB. Nonimmune
  hemolytic anemias
• 1. Chemical physical agents (drugs,
  industrial, burns) 2. Infections (parasitic
  or bacterial malaria, clostridia) 3. Red
  cell fragmentation syndromes -
  hemolytic - uremic syndrome (HUS) -
  thrombotic thrombocytopenic purpura (TTP)
  - prosthetic heart valves 4. Paroxysmal
  Nocturnal Hemoglobinuria (PNH)

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Immune haemolytic anaemias

• Auto immune .H.A
• Autoimmtme haemolytic anaemias (AIHAs) are caused
  by antibody production by the body against its
  own red cells.
• They are characterized by a positive direct
  antiglobulin test (DAT) also known as the Coombs'
  test and divided into 'warm and 'cold' types
  according to whether the antibody reacts more
  strongly with red cells at 37C or 4C.
  (typically 28-31C)

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Direct Coomb's Test Is used to detect if
antibodies or complement system factors have
bound to RBC surface antigens in vivo. A blood
sample is taken and the RBCs are washed (removing
the patient's own plasma) and then incubated with
antihuman globulin (also known as "Coombs
reagent"). If this produces agglutination of
RBCs, the direct Coombs test is positive, a
visual indication that antibodies (and/or
complement proteins) are bound to the surface of
red blood cells.

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Warm AIHA

• The red cells are coated with immunoglobulin
  (Ig), usually immunoglobulin G (IgG) alone or
  with complement, and are therefore taken up by RE
  macrophages which have receptors for the Ig Fc
  fragment. Part of the coated membrane is lost so
  the cell becomes progressively more spherical to
  maintain the same volume and is ultimately
  prematurely destroyed, predominantly in the
  spleen.
• Splenomegally extravascular hemolysis
  spherocytosis Positive DAT

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WAIHA peripheral blood film showing spherocytes
and large polychromatic cells
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Cold AIHA

• The Autoantibodies are either monoclonal as in
  lymphoproliferative
  disorder, or Polyclonal as in infections
  (infectious mononucleosis)
• The Abs in cold AIHA are Usually IgM and bind to
  red cell at 28-31C (mainly in the peripheral
  circulation where the blood temperature is
  cooled)
• Both intravascular and extravascular haemolysis
  can occur
• Mild jaundice and splenomegaly
• Spherocytosis is less marked

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• Monoclonal Abs
• Are monospecific antibodies that are the same
  because they are made by identical immune cells
  that are all clones of a unique parent cell.
• Polyclonal Abs
• Are antibodies that are obtained from different B
  cell resources. They are a combination of
  immunoglobulin molecules secreted against a
  specific antigen, each identifying a different
  epitope.

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• Alloimmune hemolytic anaemias
• In these types, antibody produced by one
  individual reacts with red cells of another. Two
  important situations are
• Hemolytic transfusion reactions
• Hemolytic disease of the newborn
• Drug-induced immune hemolytic anaemias
• Antibodies directed against the drug (Antigen).
  The Ag-Ab complexes are deposited on red cells
  and make them lysed by macrophages of RE cells.

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Non-Immune Hemolytic Anemias

• Hemolytic anaemias due to mechanisms or agents
  other than antibodies /or complement e.g.
• 1. Chemical physical agents (drugs,
  industrial, burns)
• 2. Infections (parasitic or bacterial
  malaria, clostridia)
• 3. Red cell fragmentation syndromes
  - hemolytic - uremic syndrome (HUS) -
  thrombotic thrombocytopenic purpura (TTP)
  - prosthetic heart valves
• 4. Paroxysmal Nocturnal Hemoglobinuria (PNH)

Non-immune H.A Immune H.A
Negative DAT Positive DAT
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Heinz bodies

• oxidized denatured Hb.
• Appear as small round inclusions and may appear
  as projections from the cell. They are found as a
  sign of either chemical poisoning, drug
  intoxication, (G6PD) deficiency, or the presence
  of an unstable Hb.
• They vary from 1 to 3 µm. One or more may be
  present in a single cell. They are usually close
  to the cell membrane.

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Heinz bodies
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Red cell fragmentation syndromes

• These arise through physical damage to red cells
  either on abnormal surfaces (e.g. artificial
  heart valves or arterial grafts), or as a
  microangiopathic haemolytic anaemia This is
  caused by red cells passing through abnormal
  small vessels, due to deposition of fibrin and
  often associated with disseminated intravascular
  coagulation (DIC) or platelet adherence as in
  thrombotic thrombocytopenic
• purpura (TIP).
• The peripheral blood contains many deeply
  staining red cell fragments. Clotting
  abnormalities typical of DIC with a low platelet
  count are also present when DIC underlies the
  haemolysis.

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Red cell fragmentation syndromes
Microangiopathic Hemolytic Anemia (Vascular
abnormalities), showing schistocytes (fragmented
cells)
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Paroxysmal nocturnal haemoglobinuria (PNH)

• PNH is a rare, acquired, clonal disorder of
  marrow stem cells in which there is deficient
  synthesis of some protien structures in the red
  cell membrane.
• This render red cells sensitive to lysis by
  complement and the result is chronic
  intravascular haemolysis, classically at night
  because of the low blood pH.
• The urine is red due to the appearance of Hb.
• PNH is diagnosed by the acidified-serum lysis
  Test (or the Ham's Test). Recently, it is
  diagnosed by flow cytometry.

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Laboratory diagnosis

• 1. Indirect diagnosis not specific
• Reticulocytes count increased
• Haptoglobin Reduced
• Unconjugated Bilirubin Increased
• Urine urobilinogen Increased
• LDH Increased
• 2. For intrvascular haemolysis
• Serum free Hb present
• Methaemoglobinaemia
• Haemoglobinuria
• Haemosiderinuria
• 3. Specific tests
• Coomb's test (DAT) Positive in Immune HA
• Spherocytosis in autoimmune HA
• Osmotic fragility tests in spherocytosis
• Screening for G6PD deficiency in drug induced HA
• Ham's Test in PNH
• Staining for Heinz bodies