Transcript 1- Non-immune hemolytic anemia

PERNICIOUS ANEMIA
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Scandinavian countries more prevalent
Disease of elderly – 5th to 8th decades
Genetic predisposition
Tendency to form antibodies against
multiple self antigens
PATHOGENESIS
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Immunologically mediated, autoimmune
destruction of gastric mucosa
CHRONIC ATROPHIC GASTRITIS – marked loss of
parietal cells
Three types of antibodies:
Type I antibody- 75% - blocks vitamin B12 and IF
binding
Type II antibody – prevents binding of IF-B12
complex with ileal receptors
Type III antibody – 85-90% patients – against
specific structures in the parietal cell
Associated with other autoimmune diseases like
autoimmune thyroiditis
DIAGNOSTIC FEATURES
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Moderate to severe megaloblastic anemia
Leucopenia with hypersegmented
neutrophils
Mild to moderate thrombocytopenia
Mild jaundice due to ineffective
erythropoiesis and peripheral hemolysis
Neurologic changes
Low levels of serum B12
Elevated levels of homocysteine
Striking reticulocytosis after parenteral
administration of vitamin B12
Serum antibodies to intrinsic factor
Introduction
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One of the reasons leading to anemia
development is when the rate of red blood cell
destruction exceeds the rate of production of
normal red blood cell from the bone marrow.
In the case of maturational (or developmental)
defect within the bone marrow, the resultant
anemia is associated with the production of low,
normal, (or even increased) numbers of abnormal
RBC’s, which do not function properly. In
other words, the primary cause of the anemia is
the malfunctioning RBC’s, whether
accompanied with decreased numbers or not.
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In hemolytic anemia, the rate of
production is usually normal to very
increased but anemia arise due to the
continuous hemolysis (destruction) of
RBC’s. In other words, the BM is going
through "effective erythropoiesis" but for
some reason, the RBC's produced are
still not doing their function properly.
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This type of anemia is different from
anemia resulting from "ineffective
erythropoiesis" where the BM is
responsible about the production of
defective and/or decreased amounts of
RBC's. Usually, the causes behind
ineffective erythropoiesis are related to
BM biological dynamics.
So, this group of conditions which results
from increased destruction of the RBC,
characterized by:
1. Reduced life span of RBS.
2. Hb and PCV are both low.
3. Increased Bone Marrow activity.
Classification
Hemolytic anemia is classified to two
major categories according to the cause
(etiology) of hemolysis. These reasons for
hemolysis are either of:
1- intrinsic natures. or
2- extrinsic natures.
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I- Intrinsic hemolytic anemia
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This is a group of anemia where the defect
causing the “hemolysis” is an internal one.
That is, the defect is caused within the RBC’s
themselves usually due to an congenital error in
the genetic make up of the cells. In other
words, the RBC’s were synthesized defective in
one or more of its vital compartments. All of the
intrinsic hemolytic anemias are inherited
disorders except for one type which is
acquired (see below).
i- Hereditary:
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As the name implies, this sub group is passed down
from the parents to their children, and it is further
sub-divided into three major groups according to the
type of defect:
1- Membrane defects:
As the name suggests, this group of anemia have a
malfunction in their membrane components. These
include:
Hereditary Spherocytosis.
Hereditary elliptocytosis.
Hereditary stomatocytosis (Hydrocytosis).
2- Enzyme defects:
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The diseases in this group are referred to as
“Hereditary Erythrocyte Enzymopathies”. This is a
group of anemia caused by the quantitative or
qualitative abnormalities of one or more crucial
functional enzymes leading to abnormally
functioning RBC’s, and hence anemia. This group
includes anemia such as:
Glucose-6-Phosphate Dehydrogenase (G6PD)
deficiency.
Pyruvate Kinase deficiency.
Glutathione Reductase deficiency.
3- Hemoglobinopathies:
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This is a group of diseases caused by
defective globin chains synthesis usually
leading to unstable or very fragile
hemoglobins. The group contains a large
number of unstable hemoglobins. Some
of the most important types of this anemia
are: Sickle cell anemia (SS), CC disease ,
SC disease, and S-β thalassemia.
ii- Acquired:
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Acquired intrinsic hemolytic anemia is
not common with only one known anemia
called the Paroxysmal Nocturnal
hemglobinuria (PNH).
II- Extrinsic Hemolytic Anemia
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This is a group of anemia where the defect
causing the “hemolysis” is an external one. That
is, the defect is caused by some agent(s) outside
the components of the RBC’s themselves.
Usually this is caused by: other organ failures (as
seen most frequently with the kidneys and liver),
an invading organism, auto immune diseases, etc.
In other words, the RBC’s were synthesized
normally (whether in numbers or in quality
and function) but for some reason the cells
are being attacked and destructed by other
tissues (kidneys, liver, spleen, macrophages,
etc.) or some foreign invading organisms.
 Extrinsic hemolytic anemia is also classified
to hereditary and acquired causes however
unlike the intrinsic ones, the acquired are
the most frequently encountered.
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1- Hereditary:
Rarely seen, there are only two types of this anemia.
2- Acquired:
Under this classification, a large number of factors can
lead to the development of hemolytic anemia. These
include:
Hypersplenism.
Hypertension.
Liver and/or renal diseases.
Auto Immune.
Infectious agents.
Mechanical, thermal, and/or chemical damage.
Unlike HS and G6PD deficiency hemolytic
anemias, the group of hemolytic anemias under
this category, are all acquired (not hereditary
transmitted). On contrast, to HS and G6PD the
majority of this group of anemias are caused by,
an extrinsic defects (factors leading to
hemolysis).
 The group is further sub-divided to the nature of
the pathophysiology involved, into two major
categories:
1- Those of non-immune nature
2- Those caused by immunologic defects,
known as Immune Hemolytic Anemia (
IHA).
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1- Non-immune hemolytic
anemia
The majority of this class of anemia is caused
by external factors (outside the RBC’s
themselves) affecting the small blood vessels.
 The classical and most frequently known cases
are referred to as the MicroAngiopathic
Hemolytic Anemia (MAHA).
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Examples of such hemolytic anemias are seen in:
1- Disseminated Intravascular Coagulation (DIC)
2- March Hemoglobinurea (very rare with no pb
evidence of hemolysis)
 It is extremely important to distinguish between
the above-mentioned types and the Paraxosymal
Nocturnal Hemoglobinurea (PNH), which is an
acquired defect but of INTRINSIC nature (i.e.,
the defect is within the RBC’s themselves).
2- Acquired Immune hemolytic
Anemia (AIHA)
This group is sub-classified to three major
classes:
 A- Alloimmune
 B- Autoimmune
 C- Drug Induced
1-ALLOIMMUNE
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This class includes two types of anemias:
1.
Hemolytic Disease of the Newborn (HDN).
2.
Hemolytic Transfusion Reactions
2-AUTOIMMUNE
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This class encompasses a large range of
hemolytic anemias, which are subcategorized according to the nature of
the “antibodies” involved to three types:
Cold antibody
Warm antibody
Paraxosymal cold hemoglobinurea
(PCH).
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The anemias of each of these classes
could be either Primary (idiopathic, i.e.,
caused by unknown factors) or Secondary
to known factors such as:
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Chronic Lymphocytic Leukemia (CLL)
Viral infections
Lymphoma
Infectious Mononucleosis (Epstein-Barr Virus)
Syphilis
Systemic Lupus erythematosus (SLE)
Mumps, Measles, and Chicken pox.
3-DRUG-INDUCED
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Certain drugs have been associated with
hemolytic reactions. Examples of such
drugs are Hapten, and alpha-methyldopa.
Site of hemolysis
Hemolysis of RBC’s can occur either intravascularly or extra-vascularly.
 Most of the destruction of normal or
abnormal RBC’s occurs in the ReticuloEndothelial System (RES), which include
the spleen, liver, lymph nodes, lungs, and
the bone marrow.
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Extra-vascular hemolysis
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Is the type of hemolysis where whole
intact RBC’s or their fragments are
destroyed by macrophages of the RES
ending in the release of hemoglobin
into the macrophages. Most of the
hemolytic anemias are characterized
by such hemolysis.
Intravascular hemolysis
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occurs when RBC’s are destroyed within the blood
vessels before reaching the RES. This might
occur when the damage to the RBC’s is very
severe.
Such hemolysis is rarely seen in hereditary
hemolytic anemias, but is more associated with
acquired cases such as hemolytic reaction due to
mismatched ABO blood grouping transfusions
(transfusion reaction), MicroAngiopathic
Hemolytic Anemia (MAHA), heart valves
diseases, malarial infestation, clostridium
septicemia, severe kidney and liver diseases.