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DEFINITION:
Reduction in the oxygen transport
capacity of the blood
Reduction below normal limits of
the total circulating red cell mass.
CLASSIFICATION OF ANEMIA
ACCORDING TO UNDERLYING
MECHANISM
Blood Loss
1. Acute: trauma
2. Chronic: lesions of gastrointestinal tract, gynecologic
disturbances
Increased Rate of Destruction
( Hemolytic Anemia )
Impaired Red Cell Production
ACUTE BLOOD LOSS
The alterations reflect principally the
loss of blood volume rather than the
loss of hemoglobin.
IF THE PATIENT SURVIVES
Triggersinthe
Reduction the
Triggersinthe
Reduction
production
oxygenation the
of
production
tissues of
oxygenation
erythropoietin
tissues
erythropoietin
Internal blood loss
(peritoneal cavity) the iron
can be recaptured
External Iron is lost
deficiency when insufficient
reserves are present.
CHRONIC BLOOD LOSS
Induces Anemia only when
1. Rate of Loss Exceeds Regenerative
Capacity of BM
2. Iron reserves are depleted
HEMOLYTIC
ANEMIA
INTRINSIC (INTRACORPUSCULAR)
ABNORMALITIES OF RBC
Hereditary :
A. Red cell membrane disorders
A. Antibody mediated
1. Isohemagglutinins: transfusion
reactions, erythroblastosis fetalis
2. Autoantibodies: idiopathic
(primary),drug-associated, SLE,
malignant neoplasms, mycoplasmal
infection
B. Mechanical trauma to red cells
1. Microangiopathic hemolytic anemias: -
thrombotic thrombocytopenic purpura,
DIC
2. Cardiac traumatic hemolytic anemia
C. Infections: malaria
D. Chemical injury: lead poisoning
E. Sequestration in mononuclear phagocyte
system
Hypersplenism
IMPAIRED RED
CELL
PRODUCTION
I. DISTURBANCE OF PROLIFERATION AND
DIFFERENTIATION OF STEM CELLS:
Aplastic anemia
Pure red cell aplasia
Anemia of renal failure
Anemia of endocrine
disorders
II. DISTURBANCE OF PROLIFERATION
AND MATURATION OF ERYTHROBLASTS
A. Defective DNA synthesis:
1. Deficiency or impaired use of vitamin B12 and
folic acid (megaloblastic anemias)
B. Defective hemoglobin synthesis
1. Iron deficiency
2. Thalassemias
C. Unknown or multiple mechanisms:
Sideroblastic anemia, Anemia of chronic
infections, Myelophthisic anemias due to
marrow infiltrations
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HEMOLYTIC ANEMIAS
HEMOLYTIC ANEMIAS
CHARACTERISTICS:
Shortening of the normal red cell life span
Accumulation of the products of hemoglobin
catabolism
A marked increase in erythropoiesis within
the bone marrow
PATHOGENETIC CLASSIFICATION OF
HEMOLYTIC ANEMIA
1. Extracorpuscular mechanism
Intracorpuscular defect).
2. Hereditary and Acquired
disorders.
Hereditary disorders are due to
intracorpuscular defects
Acquired disorders to extrinsic factors
such as autoantibodies.
PATHOGENETIC CLASSIFICATION OF
HEMOLYTIC ANEMIA
3. INTRAVASCULAR/
EXTRAVASCULAR HEMOLYTIC
ANEMIA
INTRAVASCULAR
Hemolytic Anemias
Less Common
Type
NORMAL ERYTHROCYTES ARE
DAMAGED BY
1. Mechanical injury
2. Complement fixation
More Common
Type
PATHOLOGY
RBC DESTRUCTION OCCUR
WITHIN THE
RETICULOENDOTHELIAL
SYSTEM
1. Rendered 2.Less
Foreign Deformable
FEATURES
NO Hemoglobinemia,
Hemoglobinuria, and other related
intravascular changes
POSITIVE Anemia and Jaundice
Splenomegaly
Plasma Haptoglobin levels are
Invariably reduced (some Hgb escape
phagocytes )
STANDARD MORPHOLOGIC CHANGES IN THE HEMOLYTIC ANEMIAS ( BOTH
TYPES ):
HEREDITARY
INTRINSIC H.A.
MEMBRANE CYTOSKELETON D/O
FEATURES
European extraction
Approximately 75% autosomal dominant
pattern.
Intrinsic defect in the red cell membrane
Renders erythrocytes spheroidal,
Less deformable,
Vulnerable to splenic sequestration and destruction
MOLECULAR PATHOLOGY
A deficiency of spectrin
The spectrin content of these cells
varies from 60% to 90% of normal and
correlates closely with the severity of
spherocytosis.
MOLECULAR PATHOLOGY
Mutations diminish "vertical"
interactions that serve to connect the
membrane cytoskeleton to the overlying
lipid bilayer
Resulting in Loss membrane fragment
Spherocyte.
Loss of membrane
fragments during
exposure to shear
stress in the circulation
MORPHOLOGY
HEREDITARY RECESSIVE X-
LINKED
INTRINSIC H.A.
RBC ENZYME DEFICIENCY
REVIEW OF RBC
BIOCHEMISTRY
Vulnerable to
RBC Deficiency injury by effects
Hemolysis
in G6PD of Oxidizing
agents
THE HEMOLYTIC SUSCEPTIBILITY
INCREASE GREATLY DURING :
1. Intercurrent Illness
2. Exposure to Various Drugs that have
oxidant properties
SULFAMETHOXAZOLE
NITROFURANTOIN
PRIMAQUINE
Denaturation
of hemoglobin
Formation of
precipitates
(Heinz bodies)
EFFECTS OF HEINZ TO RBC
Decrease erythrocyte deformability.
pass through the splenic cords pluck out the
Heinz bodies appear to have a bite of
cytoplasm removed
The resultant loss of membrane more
membrane damage induces the formation of
spherocytes.
All these changes predispose the red cells to
become trapped in splenic cords and destroyed by
erythrophagocytosis.
CLINICAL FEATURES
Acute Intravascular Hemolysis present upon exposure to
the oxidant injuries 2-3 days lag
Only senescent red cells are lysed,
Episode is self-limited and hemolysis stops when only the
younger red cells remain in the circulation (despite
continued administration of the oxidant drug).
Mediterranean variant have much lower levels of G6PD,
their anemia is more severe.
2 FORMS :
G6PD A- In Black the variant A is prevalent with normal
activity
BUT 11% 0f Blacks have type A with only 5-15% of normal
enzyme activity More susceptible to HEMOLYSIS after
ingestion Oxidant drugs/ Infection
G6PD Mediterranean
Middle East
Protects against Malaria
The level of G6PD activity in affected males is LOW (<1%)
BUT MAY HAVE A MORE SEVERE AND NON-SELF LIMITED
HEMOLYTIC ANEMIA WITH INFECTIONS & WIDER VARIETY OF
DRUGS
LABORATORY FINDINGS
ACTIVE HEMOLYSIS
SIMILAR TO HEMOLYTIC ANEMIA
( Both Typres )
HEINZ BODIES- methyl violet stain
Often attach to rbc membrane
PROTOTYPE OF HEREDITARY
HEMOGLOBINOPATHIES
PATHOLOGY
Point mutation
Substitution of valine for glutamic acid at 6th AA position
in Beta Globin chain
PATHOGENESIS:
On deoxygenation, the HbS molecules
undergo aggregation and polymerization.
This change converts hemoglobin from a
freely flowing liquid to a viscous gel,
Leading ultimately to formation of HbS
fibers and resultant distortion of the red cells,
which acquire a sickle or holly-leaf shape
EFFECT:
HbS Polymerization of B globin chain during
Deoxygenation Sickling
PATHOLOGY:
Sickling of red cells is initially a reversible phenomenon; with
oxygenation, HbS returns to the depolymerized state.
However, with repeated episodes of sickling and unsickling,
membrane damage ensues and the cells become irreversibly
sickled.
These deformed cells retain their abnormal shape even when
they are fully oxygenated and despite deaggregation of HbS
INCIDENCE:
Highest – African Decent
About 8% of black Americans are heterozygous
for HbS.
Heterozygote
40% is HbS & 60% Normal hemoglobins.
Offer slight Protection against falciparum malaria
INCIDENCE:
In Homozygous HbS disease
Almost all the hemoglobin in the erythrocyte is
HbS.
A Serious Chronic Hemolytic Anemia
Manifest Early childhood
Often fatal before 30y/o
DESCRIPTION :
Hemoglobin, as you recall, is a tetramer of four
globin chains comprising two pairs of similar
chains, each with its own heme group.
The hemoglobin in the adult is composed of 96%
HbA (a2b 2 ), 3% HbA2 (a2d2 ), and 1% fetal
hemoglobin (a2g2 ).
Structurally abnormal (defective) Hgb
THE PRECIPITATION OF HBS FIBERS ALSO HAS
DELETERIOUS EFFECTS ON THE RED CELL
MEMBRANE.
Damage both sickled & normal rbc
With membrane injury, the red blood cells
Rbcloaded w/ Ca++
Ca++ Activates K ion channel
Efflux of potassium and water and at the same time gain calcium
Rbc Dehydrated with increased MCHC
More dense
VASO-OCCLUSIVE EPISODES
ProgressiveInfarction Fibrosis Contraction of Spleen
( AutoSplenectomy )
Bone Necrosis
APLASTIC CRISIS
Temporary cessation of bone marrow activity, usually triggered by
parvovirus infection of erythroid progenitor cells.
Reticulocytes disappear from the peripheral blood, and there is sudden
and rapid worsening of anemia.
BLOOD PICTURE
Normochromic & Normocytic Anemia
Numerous target cells
Howell-Jolly bodies
Sickled rbc
BM Hyperplasia
THALASSEMIA
SYNDROMES
Heterogenous group of Inherited D/O
Genetic Lesions
Decreased Synthesis of either a or b- globin chain of HbA
(a2b2)
FEATURES:
Beta Thalassemia
Deficient synthesis of beta chain
Fress alpha chains tend to aggregate INSOLUBLE
INCLUSIONS
Alpha Thalassemia
Deificient alpha chain
As a consequence, free chains tend to aggregate
into insoluble inclusions within erythrocytes
Premature destruction of maturing erythroblasts within
the marrow (ineffective erythropoiesis)
Insoluble Inclusions rigid rbc Lysis of mature red
cells in the spleen –(hemolysis).
BETA-THALASSEMIAS
Total lack or Reduction in the synthesis of
structurally normal beta -globin chains with
unimpaired synthesis of alpha chains
Types :
Low Hemoglobin
Increased RBC
Low MCV & MCHC – Microcytic Hypochromic
Anisocytosis with N-rbc
Retic count is LOW <10%
Electrophoresis
High HgF & HgA2
Limited amount of HgA
Thalassemia major