ANEMIA

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

     1.  Disorders of membrane cytoskeleton: -

spherocytosis, elliptocytosis
      2. Disorders of lipid synthesis: - selective
increase in membrane lecithin
   B. Red cell enzyme deficiencies

     1. Glycolytic enzymes: - pyruvate

kinase deficiency, hexokinase deficiency
     2. Enzymes of hexose monophosphate shunt: -
G6PD, glutathione synthetase
   
 C. Disorders of hemoglobin synthesis
      1. Deficient globin synthesis: -
thalassemia syndromes
      2. Structurally abnormal globin synthesis
(hemoglobinopathies): - sickle cell
anemia, unstable hemoglobins
 Acquired:
    A. Membrane defect: -
Paroxysmal nocturnal hemoglobinuria
 EXTRINSIC (EXTRACORPUSCULAR)
ABNORMALITIES

 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
Click icon to add picture
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

3. Exogenous toxic factors.

 MANIFESTATIONS
(1) Hemoglobinemia,
(2) Hemoglobinuria &
(3) Methemalbuminemia,
(4) Jaundice/ Anemia
(5) Hemosiderinuria
 EXTRAVASCULAR
HEMOLYTIC ANEMIA

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 ):

1. Marked increase in the numbers of normoblasts in

the marrow
2. May lead to extramedullary hematopoiesis.
3. The accelerated compensatory erythropoiesis
leads to a prominent reticulocytosis in the
peripheral blood.
4. The elevated levels of bilirubin, when it is
excreted through the liver = pigment gallstones
(cholelithiasis).
5. With chronicity  hemosiderosis
HEREDITARY SPHEROCYTOSIS (HS)

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

 Spheroidal shape of the red cells, apparent on smears

 abnormally small cells lacking their central zone of pallor (Fig. 14-6) .

 Spherocytosis, although distinctive, is not pathognomonic,

since it is also seen in autoimmune hemolytic anemias.
CLINICAL MANIFESTATION
1. Anemia
Chronic Hemolytic Anemia
Mild to moderate severity.
Aplastic / Hemolytic crisis
2. Splenomegaly
Moderate splenic enlargement is characteristic
of HS (500 to 1000 gm);
3. Jaundice
 Most patient have a Chronic Hemolytic Anemia, usually
of mild to moderate severity.
May be punctuated by an aplastic crisis (triggered
usually by a parvovirus infection of the marrow red
cell precursors
 Sudden Worsening of Anemia due to temporary
suppression of red cell production

Some show “ Hemolytic Crisis" resulting from accelerated
red cell destruction, but clinically it is less significant than the
aplastic crisis

 Diagnosis of HS is based on family history, hematologic findings, and

laboratory evidence of spherocytosis manifested by osmotic fragility
 since there is little margin for expansion of red cell volume without rupture.
 LABORATORY
Similar to Chronic Extravascular
Hemolysis
Direct Antiglobulin test is Negative
Increased Osmotic Fragility test
Spherocytes in the Smear
Decreased or Absent central Pallor
MCV normal (Normocytic Anemia)
MCHC Often Increased reflecting a
Decrease in Cell Surface
OSMOTIC FRAGILITY TEST
 RBC are suspended in a series of tubes
contaning hypotonic sol’n of NaCl varting
from 0.9% - 0.0%
 Then incubated at room temp for 30 mins
 Then centrifuged % Hemolysis in the
supernatant soln is measured
OSMOTIC FRAGILITY TEST
 Spherocytes  have limited capacity to
expand in Hypotonic Solutions  Lyze at a
higher concentration of NaCl than biconcave
RBC
 Test is NOT specific for HS
 It may occur in Acquired Spherocytic
anemias
Autoimmune Hemolysis
GLUCOSE -6PD DEFICIENCY

HEREDITARY RECESSIVE X-
LINKED
INTRINSIC H.A.
RBC ENZYME DEFICIENCY
REVIEW OF RBC
BIOCHEMISTRY

Normally G6PD is highest in young

rbc and Decreases as it ages in person
with G6PD deficiency
G6PD – Defense against oxidant
injury
The reduced glutathione so
generated protects against
oxidant injury by catalyzing
the breakdown of oxidant
compounds like H2 O2 .
 G6PD DEFICIENCY- PATHOLOGY

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

The hemolysis in G6PD deficiency is both

intravascular and extravascular.
PATHOPHYSIOLOGY :
Infection / Oxidation of the
Exposure to sulfhydryl groups
oxidants of the globin chains

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


QUANTITATIVE ASSAY OF G6PD

RECOVERY G6PD DEFICIENCY
 The recovery phase is heralded by reticulocytosis,
as in the case of other hemolytic anemias.
 Since hemolytic episodes related to deficiencies
of G6PD occur in most patients only when there is
oxidant injury, the morphologic changes
encountered in most chronic hemolytic anemias
are rarely present.
SICKLE CELL
DISEASE
STRUCTURALLY ABNORMAL GLOBIN
SYNTHESIS

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

 Renders cell more sticky  Microvascular occlusion

FACTORS THAT AFFECT SICKLING
 The rate of HbS polymerization is also significantly
affected by the hemoglobin concentration per cell, that is,
the mean corpuscular hemoglobin concentration
 The higher the HbS concentration within the cell, the
greater are the chances of contact and interaction between
HbS molecules. Thus, dehydration, which increases the
MCHC, greatly facilitates sickling and vascular occlusion
FACTORS THAT AFFECT SICKLING
 In Heterozygous 40% of the hemoglobin is HbS, the rest
being HbA, which interacts only weakly with HbS during
the processes of gelation.
 Therefore, the heterozygote has little tendency to sickle,
except under conditions of severe hypoxia.
 In contrast, the homozygote, with virtually undiluted
hemoglobin of the S type, has full-blown sickle cell
anemia.
FACTORS THAT AFFECT SICKLING
 Finally, a fall in pH, by reducing the oxygen affinity of
hemoglobin, can increase sickling because it enhances the
amount of deoxygenated HbS.
 Hemolysis Occurs Extravascularly & some Intravascularly
due to increased mechanical fragility
 CLINICAL MANIFESTATION
 1st
several months of life – Initially
Asymptomatic ( HbF)
 Severe Anemia
 Bone changes due to BM hyperplasia
Expansion of marrow space
Thinning of the Cortex
Radial Striations in Skull ( x-ray )
Leg Ulcers
 Chronic Hyperbilirubinemia
CLINICAL MANIFESTATION
 Vasoocclusive Complications
Painful crises,
Chest, Abdomen, Bone
Episodes of hypoxic injury and infarction
Associated with infection, dehydration, and
acidosis (all of which favor sickling) has been
noted
CLINICAL MANIFESTATION
 Increased Susceptibility to infection
 (1) splenic function is impaired because erythrophagocytosis
interferes with the ability of the spleen to clear bacteria;
 (2) in later stages, total splenic fibrosis removes an important filter of
blood-borne microorganisms; and
 (3) defects in the alternative complement pathway impair
opsonization of encapsulated bacteria such as pneumococci and
Haemophilus influenzae.
 Septicemia and meningitis caused by these two organisms are the
most common causes of death in children with sickle cell anemia.
COMPLICATIONS:
 HAND-FOOT SYNDROME
 Bilateral painful swelling of the hands due to capillary stasis
 SEQUESTRATION CRISIS
 Sudden pooling of Blood and Rapid Splenomegaly
 Result to Hypovolemic Shock
 May occur in Early childhood
 COMPLICATIONS:
 FUNCTIONAL ASPLENIA
 Inadequate Antibody Responses
Impaired Ability of the RES to Clear Bacteria
 Increase risk to Infection
 acute chest syndrome

 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

 Hematocrit is Unreliable estimate of anemia

 Due to Air Trapping
 Osmotic Fragility is Decreased
 Neutrophilia & Thrombocytosis

 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 :

(1) beta0 -thalassemia, associated with total

absence of beta-globin chains in the
homozygous state; and
(2) beta+ -thalassemia, characterized by
reduced (but detectable) beta-globin synthesis
in the homozygous state.
PATHOGENESIS:
 Most of these result from point mutations.
 Impaired beta-globin synthesis contributes to the
pathogenesis of anemia by two mechanisms .
 1. Lack of adequate HbA formation,
 (MCHC) is lower
 Cells are hypochromic. Much more important

 2. Decreased survival of red cells and their

precursors, resulting from an imbalance between
alpha- and beta-chain synthesis.
 PATHOGENESIS
DECREASED SURVIVAL OF RBC
 Damage to the RBC
 Inclusion Damage
a) Cell membrane damage  Loss of K+ and Impaired DNA
synthesis
b) Reduces its plasticity  Sequestered by spleen
( Hemolytic Component )
 Apoptotic death of red cell precursors within the bone
marrow, a phenomenon called ineffective erythropoiesis
TYPES:
Beta Thalassemia Major
Homozygous for beta-thalassemia genes
Beta+/beta+ or beta 0/beta 0
Have Severe Transfusion Dependent Anemia
CLINCAL MANIFESTATION :
Beta- thalassemia minor or beta-
thalassemia trait.
The presence of one normal gene in the
heterozygotes (beta+ /beta or beta0 /beta)
usually leads to enough normal beta-
globin chain synthesis so that the affected
individuals are usually asymptomatic with
only a mild anemia
CLINICAL MANIFESTATION:
 Beta- thalassemia intermedia.
 Intermediate degree of severity
Patients have severe anemia, but not
enough to require regular blood
transfusions.
THALASSEMIA MAJOR
 Thalassemia major

Manifest 6 to 9 months after birth

 When hemoglobin synthesis switches from HbF
to HbA.
Anisocytosis (variation in size) with many
small and virtually colorless (microcytic,
hypochromic) red cells.
 Thalassemia major

Growth retardation and die at an early age

from the profound effects of anemia unless
transfused
Blood transfusions not only improve the
anemia but also suppress secondary features
related to excessive erythropoiesis.
 Thalassemia major

Cardiac disease resulting from

progressive iron overload and secondary
hemochromatosis is an important cause of
death even in patients who can otherwise
be supported by blood transfusions
 Thalassemia major
Enormous expansion of BM  Thinning of Cortex
a) Frontal & Maxillary Bossing - thinning of
the cortical bone with new bone formation on
the external aspect, giving rise to the "crew- cut"
appearance on x-rays
Marked hepatosplenomegaly
Hemosiderosis or hemochromatosis a)
compensartory increased dietary iron uptake
( Tx iron chelators )
 Thalassemia major
Management

 Iron chelators. & Transfusion

 With transfusions and iron chelation, many patients
survive into the third decade, but the overall outlook
continues to be grim.
Bone marrow transplantation from an HLA-identical
sibling is currently the only therapy that offers a
cure.
Prenatal diagnosis is possible by molecular analysis
of DNA.
Prognosis poor – No known Cure
 Thalassemia major

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

Target cells (so called because the small

amount of hemoglobin collects in the center),
Stippled red cells, and Fragmented red cells,
are common.
Reticulocyte count is lower than would be
predicted from the severity of anemia.
 Due ineffective erythropoiesis,
Hydrops Fetalis.
 This is the most severe form of alpha-thalassemia,
 Resulting from the deletion of all four alpha-globin
genes.
 In the fetus, excess gamma-globin chains form tetramers
(hemoglobin Bart)
 have extremely high oxygen affinity but are unable to
deliver the oxygen to tissues.
 With intrauterine transfusion, many such infants
can be saved.
 The fetus shows severe pallor, generalized edema,
and massive hepatosplenomegaly similar to that
seen in erythroblastosis fetalis
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
GPI – LINKED MEMBRANE PROTEINS
GPI-linked proteins that regulate
complement activity
 1. Decay-accelerating factor, or CD55;
 2. Membrane inhibitor of reactive lysis, or
CD59;
 3. C8 binding protein
 CD59 is the most important because it
limits spontaneous in vivo activation of the
alternative complement pathway by rapid
inactivation of C3 convertase.
PATHOLOGY : REVIEW
 Because several GPI-linked proteins
inactivate complement, their absence
renders blood cells unusually sensitive to
lysis by endogenous complement.
FEATURES:
 Acquired Abnormality of Multipotential Stem Cell
 Mutation of Phosphatidylinositol glycan-class A gene
 Chromosome Xp22.1
 Leads to DISRUPTION OF PROTEIN ANCHORING on
RBC Membrane
 Deficient in : 1. Decay
Accelerator Factor CD55 2. Membrane
Inhibitor of Reactive Lysis CD59 3. C8 Binding
Protein
 Leads to EPISODIC COMPLEMENT –MEDIATED
INTRAVASCULAR HEMOLYSIS
FEATURES: LABORATORY
 Episodic Normocytic or Macrocytic
Anemia
 Reticulocytosis
 Often Leukopenia & Thrombocytopenia
 - Platelets and Granulocytes are also more sensitive to
lysis by complement.
 Hemoglobinuria 20 to Intravenous
hemolysis
 Flow Cytometry
CLINICAL:
 25% ( Intermittent )Paroxysmal & Nocturnal
Intravascuar Hemolysis
 75% chronic hemolysis without dramatic
hemoglobinuria
 Hemosiderinuria with loss of iron eventually leads to
iron deficiency.
 Increased risk for Thrombosis & Bleeding -
Fatal in 50%
 May progress to Leukemia and Aplastic anemia
IMMUNOHEMOLYTIC
ANEMIA
Caused by Extracorpuscular Mechanisms
Classification:
Warm Antibody type
Cold Agglutinin type
Cold Hemolysins (Paroxysmal Cold
Hemoglobinuria)
WARM
ANTIBODY TYPE
The antibody is of the IgG type, does not usually
fix complement, and is active at 37°C.
Primary or idiopathic
Secondary to Lymphomas
and leukemias Other neoplastic
diseases  Autoimmune disorder
(SLE) Drugs
Warm Antibody Hemolytic Anemia.
Most common 40-70% Immune
hemolytic anemia
About 50% are Idiopathic or primary
 Most of the autoantibodies are of the
immunoglobulin (Ig) G class
◦ Mostly Extravascular Hemolysis- Recognized
by Fc receptors on Splenic Macrophages
◦ Producing Spherocytes
◦ Moderate Splenomegaly
Warm Antibody Hemolytic Anemia.
Common in Women
Drug – Induced Theory:
1. Hapten model( penicillin &
cephalosphorin )
◦ Induce antibody directed against the cell-
bound drug
2. Autoantibody model ( methyldopa )
◦ Initiates the prodn. of Ab that are directed
against intrinsic red cell antigens, in particular
the Rh
Blood Picture & Tx:
Normocytic or Macrocytic Anemia
Spherocytes
(+) Direct Coombs test
◦ Patient’s rbc + Anti-human globulin serum
◦ Incubated  Agglutination
Corticosteroids
Refractorycases : - With
Splenectomy or Transfusion
 COLD AGGLUTININ TYPE- IGM

Less common than warm Ab

Acute – Mycoplasma, IM
Chronic / Idiopathic
Lymphoma
The antibodies are IgM and are most active in
vitro at 0 to 4°C.( Agglutinate rbc at low
temp). Antibodies dissociate at 30°C or above.
The antibody fixes complement at warmer
temperatures, but agglutination of cells by IgM
and complement occurs only in the peripheral
cool parts of the body.
 Cold Agglutinins: IgM type
Bind to & agglutinate rbc
in cooler peripheral blood
and can fix Complement
Extravascular Hemolysis
◦ Due to binding by
Complement receptors in
liver
◦ Seen in warmer blood of
central circulation
Intravascular Hemolysis
◦ Due to Complement
Activation
 Cold Hemolysin: IgG type
Idiopathic
Secondary to infection/ Lymphoma
Generally Do Not demonstrate Prominent
Hemolysis
Most develop Peripheral vascular symptoms on cold
exposure- thrombosis ( Raynaud’s phenomenon )
Laboratory:
1. Rbc agglutinate at room temp  Lead to:
1. Falsely High MCV & MCHC
2. Falsely Lowered Hematocrit
2. Warming blood to 37C  Reverses Agglutination
 Cold Hemolysin Hemolytic Anemia.
Paroxysmal cold hemoglobinuria,
Acute intermittent massive hemolysis,
frequently with hemoglobinuria, after
exposure of the affected patient to cold
Least common
Lysis is clearly complement dependent.
AutoAntibody are IgG type that bind P
blood group antigen on rbc at low temp. 
Also known as Donath Landsteiner Ab
Cold Hemolysin Hemolytic Anemia.
Complement mediated intravascular
hemolysis does not occur until the rbc
recirculaye to warm central regions as
complements ‘ enzymes are more efficient
at 37 degrees.
Unknown Autoantibodies prod’n.
Hx of infections such as mycoplasmal
pneumonia, measles, mumps, and some
ill-defined viral and "flu" syndromes
HEMOLYTIC ANEMIA RESULTING
FROM TRAUMA TO RED CELLS
Pathogenesis:
1. Cardiac valve prosthesis
( Traumatic)
Rbc shear stresses 20 Turbulent
blood flow and Abnormal pressure
gradients caused by the valves.
Pathogenesis:
2. Narrowing or Obstruction of
vasculature
◦ Mechanical damage to the red cells
a) Most often caused by widespread
deposition of fibrin in the small
vessels in association with
disseminated intravascular
coagulation
b) Other causes of microangiopathic
hemolytic anemia -
Malignant hypertension, - SLE
-Thrombotic
Thrombocytopenic purpura (TTP)
- Hemolytic-Uremic Syndrome (HUS)
- Disseminated Cancer.
