Transcript MLAB 1315- Hematology Fall 2007 Keri Brophy

MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 17:
Hemolytic Anemia: Immune Anemias
Classification of Immune Hemolytic
Anemia’s
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Autoimmune hemolytic anemia
Drug-induced hemolytic anemia
Alloimmune hemolytic anemia
Role of Complement
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Group of serum proteins that interact with each other to
bring about complement-dependent, cell-mediated lysis.
Can be activated by two pathways: classical and alternate.
Classical pathway activated by antigen-antibody
complexes.
Alternate pathway triggered by certain microorganisms,
polysaccharides, liposaccharides, and cells or particles
even in absence of antibody. Still results in cell lysis.
WILL LEARN ABOUT COMPLEMENT IN
IMMUNOLOGY. DO NOT MEMORIZE PATHWAYS
NOW!
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Mechanisms of Hemolysis
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Intravascular
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Results from activation of the classic complement pathway via
immunoglobulin IgG or IgM antibodies. IgM more efficient
activator of complement
Antibodies bind to antigens on red cells and activate
complement resulting in lysis of the cell.
Extravascular
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Most common with immune-mediated hemolysis
Antibody coated or complement coated red cells are fully or
partially phagocytized by cells in the reticuloendothelial system
(RES), particularly in the spleen and liver. Partially
phagocytized cells are seen as spherocytes on the peripheral
smear.
Laboratory Findings in Intravascular
Hemolysis
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Hemoglobinemia
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Hemoglobinuria
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Haptoglobin
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Other test results include elevated lactate dehydrogenase (LDH)
levels – LDH is enzyme of red cell metabolism.
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May or may not see reticulocytosis.
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Laboratory Findings in Extravascular
Hemolysis
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Will see spherocytes on peripheral blood smear.
Serum bilirubin (indirect) may be elevated and
urobilinogen concentration may be increased in
both urine and stools.
Direct Antiglobulin Test (DAT) may be
positive, as well as indirect antiglobulin test
(antibody screening test).
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Laboratory identification of sensitized red cells
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Two major techniques
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Agglutination in saline
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Antihuman globulin(AHG) or Coombs test
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Detects IgM class of antibodies
Detects IgG class of antibodies and/or complement
Difference in the ability of IgG and IgM to cause
agglutination in saline is based on the difference in
size of the two antibodies in relation to the zeta
potential
RBC Zeta Potential
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Caused by a difference in
the charge density of the
inner and outer layers of
the ionic cloud around rbcs
when they are suspended in
saline. The force keeps
rbcs about 25nm apart in
solution. So any antibody
that causes agglutination
must be > 25nm to span the
gap between cells
RBC Zeta Potential
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IgM can span 35nm to
overcome forces, causing
agglutination
IgG spans about 14nm, so
it can not reach antigens on
separate cells to cause
agglutination. Therefore,
another technique must be
used.
Autoimmune Hemolytic Anemias
Autoimmune Hemolytic Anemia (AIHA)
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Caused by an altered immune response resulting
in production of antibody against the patient’s
own red cells, with subsequent hemolysis
These autoantibodies are directed against highincidence antigens
Mechanism of antibody formation unknown
Further classified as warm or cold hemolytic
anemia
Warm AIHA (WAIHA)
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Most common form of AIHA ~70%
Reacts best at body temperature (37oC)
Can occur at any age, but incidence increases
over the age of 40
Cases can be idiopathic or secondary to
another disease
IgG coats red cells with or without
complement fixation
Antibody usually directed against antigens of
the Rh system
Laboratory findings of WAIHA
Common Findings
Positive DAT
Normocytic, normochromic
anemia
Increased reticulocytes
Spherocytes
RBC abnormalities
Presence of autoantibody in
serum
Increased bilirubin
Decreased serum haptoglobin
Cold Autoimmune Hemolytic Anemia
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Optimal thermal activity below 30oC
Cases can be idiopathic or secondary to another disease
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Often seen secondary to Mycoplasma pneumoniae (anti-I) or infectious
mononucleosis
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Seasonal hemolytic anemia during the winter months. Usually not
severe. RBC’s agglutinate at room temperature and will be seen as
clumps on a peripheral smear.
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Mechanism of action
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IgM antibody attaches to erythrocyte in the cold and fixes complement
After warming, the antibody dissociates from the cell, but complement
reamins, causing lysis or initiating extravascualr hemolysis
Side note: Almost all adults have cold antibodies in low quantity
which cause no problems because they react in the temperature
range of 4̊ to 22̊ C. The antibody is usually anti-I.
Laboratory findings of Cold AIHA
Common Findings
Positive DAT
Normocytic, normochromic
anemia
False increase in MCV, MCH,
MCHC
False decrease in RBC count
Increased reticulocytes
Spherocytes
Agglutinated RBCs, rouleaux,
nRBCS
Cold agglutinin titer high at 4oc
Increased bilirubin
Decreased serum haptoglobin
Paroxysmal Cold Hemoglobinurea (PCH)
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Cold hemolytic anemia which can be severe
Common in children under age 5
Seen with viral and bacterial infections
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Caused by a bi-phasic complement-fixing IgG antibody( DonathLandsteiner)
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Antibody reacts with RBCs in the capillaries at temperatures < 20oC
and avidly binds early complement. Upon warming to 37oC , the
antibody molecule disperses from the cell, but the membrane attack
complement components are activated on the cell membrane causing
lysis
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Treatment is to avoid the cold
Laboratory findings of PCH
Common Findings
Decreased hgb
Hemoglobinemia
Hemoglobinuria
Methmalbuminemia
Neutropenia, reticulocytopenia
Spherocytes
Increased bilirubin
Decreased serum haptoglobin
Drug-Induced Hemolytic Anemias
Drug-Induced Hemolytic Anemia
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Drugs that attach to the RBC membrane or alter it in some
way
 Methyldopa/ procainamide, penicillin, cephalosporins
Patient produces antibodies directed against a particular drug,
its metabolites or the RBC coated with drug
Relatively uncommon
Acquired
Usually an IgM antibody
The drug itself does not cause the RBC injury, and not all
people taking the drug are affected
Alloimmune Hemolytic Anemia
Alloimmune Hemolytic Anemia
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A foreign antigen stimulates the host’s immune
system to produce a corresponding antibody
called an alloantibody
Two main types
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Hemolytic transfusion reactions
Hemolytic Disease of the Fetus and Newborn(HDFN)
Types of Alloimmune Hemolytic
Anemia
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Hemolytic transfusion reactions
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Acute transfusion reaction
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The wrong ABO type of blood is transfused. If a patient
develops symptoms such as fever, shaking, chills, pain or
burning at the site of the iv, the transfusion should be stopped
immediately.
Delayed transfusion reaction
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Sensitization to non-ABO blood groups occurs during a primary
transfusion. When re-exposed during a second transfusion,
antibodies build up and a delayed reaction occurs. Symptoms are
usually mild and non-specific.
Types of Alloimmune Hemolytic
Anemia
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Hemolytic Disease of the Fetus and Newborn
(HDFN)
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This is caused when the mother’s and baby’s blood groups are
incompatible and there is an exchange of fetal-maternal blood during
delivery. The mother builds antibodies against the fetal red cells
which then become coated with antibody and are destroyed in the
baby’s RES.
Associated with ABO or Rh incompatibility.
It can be severe and treatment would consist of an exchange
transfusion of the newborn.
Referenes
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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.
Rodak, B. F. (2002). Hematology Clinical Principles and
Applications (3rd ed.). St. Louis: Saunders Elsevier.