Download A. Immune hemolytic anemias

Acquired haemolytic
anaemias
Waggas Ahmed Elaas
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 :
1. Immune Haemolytic anaemias
2. Non – immune Haemolytic anaemias
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Classification
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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 associated
B. 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)
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 37°C or 4°C. (typically 2831°C)
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.
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
WAIHA : peripheral blood film showing spherocytes and large
polychromatic cells
Cold AIHA
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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 28-31°C (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.
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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:
1. Hemolytic transfusion reactions
2. 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.
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)
Immune H.A
Non-immune H.A
Positive DAT
Negative DAT
Heinz bodies
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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.
Heinz bodies
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.
Red cell fragmentation syndromes : Microangiopathic Hemolytic
Anemia (Vascular abnormalities), showing schistocytes (fragmented
cells)
Paroxysmal nocturnal haemoglobinuria (PNH)
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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.
Laboratory diagnosis
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Indirect diagnosis : not specific
Reticulocytes count : increased
Haptoglobin : Reduced
Unconjugated Bilirubin : Increased
Urine urobilinogen : Increased
LDH : Increased
For intrvascular haemolysis
Serum free Hb : present
Methaemoglobinaemia
Haemoglobinuria
Haemosiderinuria
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