NORMOCYTIC NORMOCHROMIC ANEMIA
CAUSES natin magkakaroon sya ng traumatic
a. After acute blood loss
b. Many hemolytic anemias
c. Anemia of chronic disease (some
cases)
d. Renal disease
e. Mixed Deficiencies
f. Bone marrow failure (post
chemotherapy, infiltration by
carcinoma, etc.)
BLOOD LOSS ANEMIA
Kinds:
1. Acute Blood Loss Anemia-
characterized by a sudden loss of
blood resulting from a trauma or
other severe forms of injury.
- clinical symptoms:
 Hypovolemia
 Rapid pulse
 Low blood pressure
 Pallor
- lab evaluation
 Normocytic normochromic
anemia
 Initially normal reticulocyte
count, hgb/hct; in a few hours,
increased in platelet count and
leukocytosis with a left shift,
drop in hgb/hct and RBC;
 Reticulocytosis in 3-5 days
* Significant blood loss - 30 to 40% total
blood volume ang nawala sa katawan
reaction.
2. Chronic Blood Loss Anemia -
characterized by a gradual long-
term loss of blood; often caused
by gastrointestinal bleeding.
- Lab evaluation:
 Initially normocytic
normochromic anemia that
over time causes a decrease in
hgb/hct;
 Gradual loss of iron causes
microcytic hypochromic
anemia.
Note: occurs after its lifespan of 120 days,
when the red cells are removed
intravascularly by the macrophages off
the reticular epithelial system (majority of
the cells are removed extravascularly that
is 90%). The cells have no nucleus and
the red cell metabolism gradually
deteriorate Kasi na dedegrade na yung
enzyme natin and they are not replace so
the cell become non-viable. So ang
nangyayari is nasa separate yung heme
sa globin, the heme will further broken
down into iron and protoporphyrin. The
iron that has been released for
recirculation via plasma transferin to the
morrow erythroblast. The protoporphyrin
will be broken down into bilirubin, the
bilirubin will goes to the liver where it can
LEMMINGS 1
 NORMOCYTIC NORMOCHROMIC ANEMIA
be conjugated to glucuronides which are destruction and the inability of the bm to
excreted doon sa bile ducts natin and respond to the stimulus of anemia. (Hindi
converted into stercobilin and inaabot ang 120 days lifespan at hindi
stercobilinogen. In this is partly kayang palitan ng BM ang nasisirang
reabsorbed in the urine in the form of cells.
urobilinogen and urobilin. Intravascular
hemolysis occurs when there is a - hemolytic disruption of the erythrocyte
destruction of red cells within the blood involves an alteration in the erythrocytic
vessels. A massive intravascular membrane. The causes of this
hemolysis is not normal because it membrane alteration can be divided into:
causes a serious problem in the blood
a. Inherited hemolytic disorders
vessels it has a problem in the red cells. If
(intrinsic hemolytic anemia) -
the destruction is intravascular the free
defects in the red cell itself.
hemoglobin and methalbumin is present
in the plasma, so the urine may also b. Acquired hemolytic disorders
contain free hemoglobin and (extrinsic hemolytic anemia) - in
hemosiderin. The free hemoglobin will be which a factor outside the
bound to haptoglobin, in intravascular erythrocyte acts on it.
hemolysis of the decreased haptoglobin
kasi marami siyang kine carry na free
hemoglobin. And this complex is
removed from the circulation and will
eventually catabolize by the liver
parenchymal cells and this process will
prevent hemoglobin from appearing in
the urine. If the plasma hemoglobin levels
will exceeds 50 to 200 mg/dl, the free
hemoglobin will pass through the
glomerulus of the kidney and the part of
the hemoglobin will be absorbed by the
proximal tubular cells where the
hemoglobin iron is converted to
hemosiderin. When this tubular cells are
later shed into the urine it will result into
hemosiderinuria. If the amount of the
hemoglobin in the tubular lumen will
exceeds the capacity of the tubular cells
to absorb it reaches the urine kaya Tayo
nagkakaroon ng hemoglobinuria. The
globin chain is broken down into amino
acid and they are recycled for protein
synthesis.

HEMOLYTIC ANEMIA

- results from an increase rate of rbc

LEMMINGS 2
NORMOCYTIC NORMOCHROMIC ANEMIA

LEMMINGS 3
NORMOCYTIC NORMOCHROMIC ANEMIA

LEMMINGS 4
 NORMOCYTIC NORMOCHROMIC ANEMIA
INHERITED HEMOLYTIC ANEMIA
Hemolytic Anemias Due to Intrinsic
Defects
A. Structural Membrane Defects - the
ability of erythrocytes to deform and
subsequently return to their original
biconcave disc shape is determined by:
 Flexibility of the membrane, which
relies on the structural and
functional integrity of the
membrane skeleton.
 Cytoplasmic viscosity determined
primarily by hemoglobin.
 Cell surface-area-to-volume ratio
 Structural proteins, forming the
erythrocyte skeleton, are alpha
and beta spectrin, actin, and
protein 4.1
 Red cell band 3 is the major
integral membrane protein that
regulates exchange and facilitate
the transfer of CO2 from tissues to
lungs.
 Ankyrin is the major connecting
protein that links the membrane
skeleton to the membrane bilayer.
Note: spectrin and ankyrin are a part of
cytoskeletal matrix protein that supports
the lipid bilayer of a red cells. They are
responsible for the elasticity and
deformity of the red cells. Red cells can
stretch up to 117% of its surface volume.
1. HEREDITARY SPHEROCYTOSIS
(hereditary hemolytic jaundice)
- it is the most common inherited
hemolytic anemia and people of northern
european descent.
- it is genetically and clinically
heterogeneous the majority of cases
result from mutations in the gene of
ankyrins.
- causes:
 An an autosomal dominant
disorder that can be caused by
any one of the severe defects in
cytoskeletal CHINs including band
3, spectrin, and ankyrin.
 This abnormally permeable cell
membrane results from a
reduction of phospholipid and
cholesterol that allows the passive
influx of sodium ions (10 times
normal rate) into the cell.
 Because of membrane
abnormality the result is
interference with rbc bi-concavity
and deformity.
 The fundamental cause of most
cases of HS is defective vertical
attachment between the
phospholipid bilayer and the
cytoskeleton scaffold, thus, the
cell has a decreased surface-area
-to-volume ratio, which changes
the shape of cell from discoid to
spherocyte.
Note: spherocyte has a reduced cellular
flexibility. So if it is not flexible it cannot
enter the microvasculature hence it will
hemolyzed.
- features:
a. Chronic hemolysis (extravascular
occurring the only in the presence
of the spleen)
b. Jaundice and splenomegaly (Kasi
naiipon yung destroyed red cells)
c. Mild anemia
d. Cholelithiasis (presence of
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 NORMOCYTIC NORMOCHROMIC ANEMIA
gallstones; common complication;
commonly seen in adults and
young adults)
- Lab evaluation:
 Hgb and hct: normal to moderate
decreased
 MCV: normal to slightly decreased;
MCH: normal; MCHC: usually
increased (the only condition in
which mchc can be truly
increased)
 Reticulocyte: 3-10%
 PBS: spherocyte and anisocytosis
 Osmotic fragility: increased (best
screening test for HS)
 Autohemolysis test: increased
 LDH and bilirubin: elevated
(extravascular hemolysis)
Note:
The osmotic fragility test,
incubated in anincubed, is the test
for choice to confirm a diagnosis
of HS.
Auto-hemolysis is increased and
corrected by glucose. The cells
are incubated with their own
plasma for 48 hrs with or without
glucose.
The direct antiglobulin (Coomb's)
test is normal, exceeding an
autoimmune cause of
spherocytosis and hemolysis.
- treatment:
 Treatment of choice is
Splenectomy.
2. HEREDITARY
ELLIPTOCYTOSIS/OVALOCYTOSIS
- an autosomal dominant disorder due to
most commonly to defective formation of
spectrin tetrameters.
- there is an excuse efflux from elliptical
cells and a normal cell membrane
sodium potassium ATP.
Note: associated in severe hemolytic
anemia of infants however majority of
patients which is 90% is non-anemic.
- features:
 Red blood cells are squeezed into
an elliptical shape as they pass
through capillaries, and eventually
RBCs in HE patients become fixed
in that shape.
 Cells have a nearly normal
lifespan.
 Patients with homozygous or
doubly heterozygous elliptocytosis
present with a severe hemolytic
anemia with microspherocytes,
poikilocytes and splenomegaly
(hereditary pyropoikilocytosis)
- types:
1. Common type
 Found in African-American
(heterozygotes have mild or no
hemolysis while the
homozygotes have moderate
to severe anemia)
 Hereditary pyropoikilocytosis
(HPP) is a variant of common
HE which is characterized by
unusual sensitivity of red cells
to heat (45 C)* (primary seen
in black people; involves two
abnormalities, defective
LEMMINGS 6
 NORMOCYTIC NORMOCHROMIC ANEMIA
assembly of the alpha and
beta spectrin tetramer and
absolute decrease in spectrin
present in RBC shape and
sizes.
Note: normal RBC can withstand up to
49C heat.
Additional laboratory evaluation of
hereditary pyropoikilocytosis:
 MCV: decreased
 Osmotic fragility test: increased
 PBS: Bizarre red cell shapes such
as RBC budding, fragments,
microspherocytes and elliptocytes.
 Heat sensitivity: RBC
fragmentation when warmed to
45C.
2. Spherocytic type
 Results from double
heterozygosity for HS and HE
3. Stomatocytic type
 A.k.a. Southeast Asian
Ovalocytosis (SAO)
 Common in Malaysia
 Due to band 3 CHON defect
and confers against P. vivax
malaria.
- Lab evaluation:
 Hgb and Hct: normal to severely
decreased
 PBS: elliptocytosis
 Retic count: slightly elevated
 Osmotic fragility: variable
 Autohemolysis test: variable
3. HEREDITARY STOMATOCYTOSIS
- cause:
 The exact membrane defect is
unknown, but study suggests that
there is an absence of a
membrane CHON located in the
band 7 region called stomatin.
 Associated with abnormal Na/K
permeability
- features:
 The cells are uniconcave.
 The MCHC is usually decreased
and the MCV may be increased.
 Anemia is usually mild to
moderate
 Bilirubin is increased and
Reticulocytosis is moderate
 Peripheral blood smears have 10%
to 50% stimatocytes
 It is also a feature of Rhnull red
cell phenotype.
 Osmotic fragility and
autohemolysis are increased.
Autohemolysis is partially
corrected with glucose and
adenosine triphosphate (ATP).
 Splenectomy yields variable
responses.
- types:
1. Hydrocytosis (over hydrated)
 More severe
 Red cells take on extra water
 Lab evaluation:
MCV: increased
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 NORMOCYTIC NORMOCHROMIC ANEMIA
MCHC: decreased spheroidal or stomatocytic.

PBS: stomatocytes  Hemoglobin F levels are often

(elongated, mouth-like elevated.
central pallor)

Osmotic fragility: increased

2. Xerocytosis
 Less severe
 Allows water to exit RBC
 Lab evaluation:
MCHC: increased
PBS: normocytic red cells
with codocytes (target
cells), mild stomatocytosis
and spiculated
dessicocytes.
Osmotic fragility:
decreased
4. RHnull DISEASE
5. HEREDITARY ACANTHOCYTOSIS
- dense contracted or spheroidal red
blood cells with multiple thorny
projections or spicules.
- acanthocytes I don't prevalent into very
different constitutional disorders:
abetalipoproteinemia and spur cell
anemia.
Note: abetalipoproteinemia it is a rare
arrangements of lipid metabolism
resulting from a genetic inability to
synthesize apolipoprotein P, a protein
that coats kylomicrons.
- cause:
 Decrease plasma and membrane
lipids resulting in irregular reform
RBCs.

- this disorder is associated with - features:

stomatocytosis, spherocytosis, and
 Develop in young children, but
deletion of all Rh-Hr determinants
adults suffer from only mild
including the Landsteiner-Weiner (LW)
anemia.
antigen from the red blood cells.
 MCV, MCH, MCHC, and osmotic
- Rhnull sales are abnormally permeable
fragility are normal.
to K and partly compensate for this
leakiness and the resultant cation - additional lab evaluation:
deficiency by reinforcing the number and
activity of Na-K ATPase pumps.  Triglycerides and cholesterol:
decreased
- features:
 PBS: Marked ACANTHOCYTOSIS
 The hgb concentration is between
11-13 g/dl  Retic count: normal to increased

 Reticulocytes are moderately

increased
B. ERYTHROCYTIC ENZYME DEFECTS -
 Many of the red blood cells are the anemia in this group are caused by

LEMMINGS 8
 NORMOCYTIC NORMOCHROMIC ANEMIA
deficiency of: - genetic isoenzyme variation
(depending on electrophoretic mobility)
a. Glucose-6-phosphate
dehydrogenase (G6PD)  Type A - individuals have clinically
mild conditions but can be
b. Pyruvate kinase (PK) affected by accidents to produce
a hemolytic crisis.
c. Methemoglobin reductase
 Type B - only only 1% and a more
susceptible to a severe oxidants
1. GLUCOSE-6-PHOSPHATE hemolysis than type A.
DEHYDROGENASE (G6PD)
- agents that may cause hemolytic
- it is a catalyst in the first stages of anemia:
oxidative portion of red cell metabolism.
 Infections and other acute
Note: glutathione is the chief RBC illnesses
antioxidant.
 Fava beans (possibly other
- inheritance pattern vegetables)

 Sex-linked  Drugs

Note: gene in G6PD is located in X - clinical features:

chromosome, so the deficiency is
inherited as an X-linked trait. Woman are  Acute anemia in response to
usually asymptomatic carrier. The human oxidant stress
purifier g6pd gene has 531 amino acid.
 Neonatal jaundice
- causes:
 Rarely, a congenital non-
 A decrease of G6PD in the MHP spherocytic hemolytic anemia
shunt prevents the production of
 Usually associated with sensitivity
NADPH for the synthesis of
to certain drugs and ingest in or
reduced glutathione which is
even inhalation of the pollen of the
required to prevent hydrogen
common European broad bean
peroxide buildup in the RBC during
(Vicia fava). Thus the disorder is
oxidant stress.
called favism.
 Increase level of H2O2 irreversibly
 G6PD is normally highest in young
denature hemoglobin resulting in
RBCs and decrease as cell ages.
heinz bodies which when traverse
the microcirculation will caused - manifestation:
hemolysis.
 Episodes of hemolysis are
 The aggregates of oxidized indicated by sudden onset of
hemoglobin are plucked out of the jaundice, palor, darker urine, and
cell by spleen, resulting in abnormal or back pain.
characteristic "bite" or "blister" cell.
- lab evaluation:

LEMMINGS 9
 NORMOCYTIC NORMOCHROMIC ANEMIA
 Hgb: drops to about 3-4 g/dl
 Retic count: increased during
hemolytic episodes
 Supravital stain of Heinz Bodies:
positive
 Serum bilirubin and lactic
dehydrogenase: increased
 PBS: presence of "bite" and
"blister" cells, polychromasia,
schistocytes, and
microspherocytes
 Haptoglobin: decreased
 Flourescent spot test for G6PD: no
flourescence
 Ascorbate cyanide test: positive
 Quantitative G6PD assay:
decreased
 Autohemolysis test: positive
2. PYRUVATE KINASE DEFICIENCY
- inheritance pattern:
 Autosomal recessive
- cause:
 A decrease of pyruvate kinase in
the EM pathway prevents
synthesis of levels of ATP needed
for adequate RBC function.
- pathophysiology:
 The human PK-LR codes for red
cells PK which is needed in the
generation of ATP through
anaerobic glycolysis.
 Erythrocyte with PK deficiency
generates less ATP and NADH
from glucose.
 There is also a decrease Na+, K+-
ATPase activity, which
consequence cellular dehydration
and results in cell shrinkage,
distortion of the shape of the cell,
and increase membrane rigidity.
 The exact mechanism of
hemolysis is unknown, but it is
thought that there are
abnormalities in membrane
function.
 The 2,3-Diphosphoglycerate
(DPG) accumulates in RBCs
(increased 2,3-DPG facilitates O2
unloading)
 This changes subsequently lead to
premature destruction of a
erythrocytes in the spleen and
liver as well as hemolytic anemia.
- clinical manifestations:
 That severity of anemia varies
widely (hemoglobin 4-10 g/dl) and
causes relatively mild symptoms
because of a shift to the right in
the oxygen dissociation curve
cause by a rise in intracellular 2,3-
diphosphoglycerate (2,3-DPG)
 Jaundice is usually gallstones
frequent.
 Frontal bossing may be present.
 Splenectomy may alleviate
anemia but does not cure it and is
indicated in those patients who
need frequent transfusions.
 Neonatal hyperbilirubinemia is
common and may require
exchange transfusion.
- additional laboratory evaluation:
 Osmotic fragility: normal
LEMMINGS 10
 NORMOCYTIC NORMOCHROMIC ANEMIA
 PBS: normochromic, normocytic
erythrocytes with varying degrees
of polychromatophilia
(reticulocytosis), presence of
echinocytes (dessicocytes) which
appear in large number only after
splenectomy.
 Incubated osmotic fragility: ofter
increased
i. Direct complement-mediated
(intravascular) hemolysis versus
phagocytosis by macrophages of
the reticuloendothelial system
(extravascular hemolysis)
ii. Warm-reactive antibodies, usually
IgG, versus cold-reactive
antibodies, usually IgM

3. METHEMOGLOBIN REDUCTASE
DEFICIENCY

- inheritance pattern:

 Autosomal recessive

- cause:

 A decrease of methemoglobin
reductase in the EM glycolytic
pathway allows Hgb to remain in
the Ferric (Fe3+) state.

 The oxidized iron molecules

cannot carry oxygen to the tissues.

Note: approximately 1% of circulating

hgb in normal individual is
methemoglobin.

- additional lab evaluation:

 Methemoglobin assay: increased

 NADH methemoglobin reductase

activity: decreased

ACQUIRED HEMOLYTIC
ANEMIA/Hemolytic Anemias Due to
Extrinsic/Immune Defects

IMMUNE HEMOLYTIC ANEMIA -

shortened RBC survival, mediated
through immune response, specifically
by humoral antibody.

- Mechanism:

LEMMINGS 11
 NORMOCYTIC NORMOCHROMIC ANEMIA
BROAD CATEGORIES
1. AUTOIMMUNE HEMOLYTIC
ANEMIAS
a. Associated with warm-type
antibodies
b. Associated with cold-type
antibodies
c. Associated with both warm-
and cold-type antibodies
2. ISOIMMUNE/ ALLOIMMUNE
HEMOLYTIC ANEMIAS
a. Hemolytic disease of the fetus
and newborn (HDFN)
b. Rh incompatibility
c. ABO incompatibility
3. DRUG-INDUCED HEMOLYTIC
ANEMIA
a. Adsorption of immune
complexes to red cell
membrane
b. Adsorption of drug to red cell
membrane
c. Induced of autoantibody to
drugs
d. Non-immunological
adsorption of immunoglobulin
to red blood cell membrane
1. AUTOIMMUNE HEMOLYTIC ANEMIA -
caused by an altered immune response
resulting in production of antibodies
against the patient's own red cells, with
subsequent hemolysis.
a. Cold-reactive immune hemolytic
anemia
 Is generally mediated by IgM
antibodies that reacts
maximally at approximately 4-
18°C.
Note: IgM antibodies may cause
intravascular hemolysis if the antibodies
present in high titer. Hemolysis in this
extravascular predominant in liver. The
IgM antibodies are large and can bridge
the distance between the RBCs, thus, the
IgM antibodies by themselves are able to
agglutinate RBCs. So, it contrast to IgG
antibodies which are smaller and alone
are not being able to agglutinate RBCs.
- causes:
1. Cold Agglutinin Disease
a. Primary
b. Secondary
b.1. infections
b.2. autoimmune disorders
b.3. lymphoproliferative
disorders
2. Paroxysmal Cold Hemoglobinuria
(PCH)
Note: Cold Agglutinins are antibodies that
cause agglutination of erythrocytes at
cold temperature. While cryoglobulins
are antibodies that aggregate at cold
temperature there is no erythrocyte
involved.
- Lab testing of autoimmune hemolytic
anemia:
 The direct antiglobulin test (DAT or
direct Coombs' test) tests for
antibody or complement on the
patient's RBCs.
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 NORMOCYTIC NORMOCHROMIC ANEMIA
 It uses the patient's cells and adds
a reagent serum.
 The antibody screen (indirect
antiglobulin test or indirect
Coombs' test) tests for
unexpected anti-erythrocyte
antibodies in patient's serum.
 The patient's serum is added to
panels of reagent red cell.
- PRIMARY [IDIOPATHIC] COLD
AGGLUTININ DISEASE
 Occurs with no obvious
participating cause. (Usually
occurs in older individual at age 70
y/o very common in women and
men; may last for months or years)
 The antibodies monoclonal,
usually IgM with kappa light chain
(IgM).
 Primary cold Agglutinin disease
thus represent a monoclonal
gammopathy.
Note: anemia associated with idiopathic
cold agglutinin disease is usually modest
the main symptoms is related with
erythrocytes and usually exposure to
colder temperature rather than anemia.
- SECONDARY COLD AGGLUTININ
DISEASE
 CAD is most often related to
infections, primarily Mycoplasma
pneumoniae or Epstein-Barr virus
(EBV) (infectious mononucleosis)
 It can occasionally occur with
other viral infections (adenovirus,
cytomegalovirus, rubella, mumps,
HIV), bacterial infections
(Legionella, E. coli, Listeria),
malaria, syphilis, and others.
 The antibodies are polyclonal and
usually directed against the "I/I
blood group". The antibody is
usually IgM and binds to red cells
best at 4°C.
 Compliment alone is usually
detected on the red cells, the
antibody having eluted off the cell
is warmer parts of the circulation.
- PAROXYSMAL COLD
HEMOGLOBINURIA (PCH)
 Three clinical forms of PCH.
1. An acute form that follows an
infection
LEMMINGS 13
 NORMOCYTIC NORMOCHROMIC ANEMIA
2. A chronic form associated with 1. Donath-Landsteiner test:
tertiary or congenital syphilis positive

3. A chronic idiopathic form 2. DAT: positive during hemolytic

episodes
 Clinical manifestations of PCH:
3. Hemoglobin: decreased
I. Patients experienced
intermittent episodes of pain in 4. Bilirubin: increased
the back, legs, or abdomen;
fever, nausea, vomiting; and 5. Urine hemoglobin: positive
headache following exposure
6. PBS: spherocyte
to cold.
7. Others:
II. The plasma maybe red during
the acute episode. The urine 1) Rosenbach test
will be dark red or black,
clearing over a few hours. The 2) Erhlich test
anemia maybe severe.
3) Sanford test
 Laboratory evaluation of PCH:

I. The DAT is positive for

complement but not for IgG.

II. The diagnosis is confirmed by 2. ISOIMMUNE/ ALLOIMMUNE

the Donath-Landsteiner test.
The patient's serum is
incubated in ice water with
group O,P+ erythrocyte and
fresh normal serum. The
mixture is warmed to 37°C,
and if the cells hemolyzed on
rewarming the test is positive.
 Cause
I. IgG autoantibodies may be of
unknown origin or secondary
to another autoimmune
disorder such as lupus or
lymphoma.
HEMOLYTIC ANEMIA
a. Hemolytic disease of the newborn
(HDN)
- cause
Fetal rbc antigens, if different
from the mother's, maybe
stimulate the mother to produce
Ab against the Ag. If the Ab is IgG,
it can cross the placenta and
hemolyzed the fetal RBCs. The
most common Ab groups
implicated in hemolytic disease of
the newborn are ABO and Rh.

II. The most common Ab specific

is anti-e.

III. IgG coats red cells with or

without complement fixation.

 Laboratory Evaluation

LEMMINGS 14
 NORMOCYTIC NORMOCHROMIC ANEMIA
b. Rh HEMOLYTIC DISEASE
 Inheritance of the three major
Rh antigens (C/c, D, E/e) is
determined by two genes on
the short arm of chromosome
1.
a. The RhD gene coding the
protein carrying the G
antigen,
b. The RHCE gene coding the
proteins carrying the C/c
antigens and E/e antigens.
Note: there is no "d" antigen; the letter
"d" designates the absence of D. All of
the offspring of homozygous Rh+ man
and Rh- women are Rh or D+.
- pathophysiology
 The presence of D-positive red
cells (Rh positive) in a D-negative
(Rh negative) mother initially
provokes a primary immune
response that is weak and slow
and consist of IgM antibodies that
do not cross the placenta
 Subsequently, anti-D IgG
antibodies capable of crossing the
placenta are produced. Repeated
exposure to Rh-positive fetal red
blood cells, as in a second Rh-
positive pregnancy in a sensitized
Rh-negative woman, produces a
secondary immune response
marked by rapid production of
large amounts of anti-D IgG anti
body by maternal memory of B
lymphocytes.
 In the absence of Rh Ig
prophylaxis, sensitization occurs
in 7 to 16% of women at risk,
within 6 months after delivery of
the first Rh-positive ABO-
cimpatible fetus, and in 2% after
delivery of an ABO- incompatible
fetus.
c. HEMOLYTIC TRANSFUSION
REACTION
- cause:
 An Ab that has been
stimulated by a foreign RBC Ag
will react with transfused RBCs
carrying the same Age.
 The reaction may be aither
immediate or delayed:
 Acute transfusion reaction:
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.
LEMMINGS 15
 NORMOCYTIC NORMOCHROMIC ANEMIA
3. DRUG-INDUCED HEMOLYTIC  The antibody is directed
ANEMIA against a red cell antigen, not
against the drug itself.
-cause:
 The DAT is positive for IgG with
 RBC hemolysis is triggered by one or without complement and
of the several mechanism in which may be positive even in the
the drug, RBC Ag, and a drug- absence of the drug. The
related Ab interact. antibody screen may be
positive.
Note: This represents approximately 10 to
20% of the immune hemolytic anemia.  A similar reaction can be seen
- mechanism: with levodopa and
procainamid
I. Drug adsorption (penicillin) type

 The drug binds tightly to the

NON-IMMUNOLOGIC ACQUIRED
rbc surface, and an anti-drug
HEMOLYTIC ANEMIA/Hemolytic
antibody reacts with the drug
Anemias Due to Extrinsic/Non-lmmune
that is bound to the red cell.
Defects
 The DAT is positive for IgG,
-MECHANICAL TRAUMA
with or without complement.
1. Malfunctioning mechanical heart
II. Neoantigen (formerly called
valve - the erythrocytes are
immune complex) type
crashed by the valve leaflets as
 There is a complex of drug and they closed resulting in
anti-drug antibody, which fragmentation and a chronic
binds to an antigen on the red intravascular hemolysis.
cell. The antibody can be either
2. March hemoglobinuria - Transient
IgM or IgG and is often
hemolytic anemia that occurs
complement fixing.
after forceful contact of the body
 The antibody of hen has with hard surfaces (e.g., marathon
relatively low avidity, it binds to runners, tennis players)
the complex on the cell
3. Microangiopathic hemolytic
membrane, fixes complement,
anemias (sometimes called
and then dissociates from the
thrombotic microangiopathies):
cell surface.
thrombotic thrombocytopenia
 The DAT is there for positive purpura (TTP), hemolytic-uremic
for a compliment but usually syndrome (HUS),
not for immunoglobulins. preeclampsia/eclampsia,
malignant hypertension,
III. Autoimmune (-methyldopa) type disseminated intravascular
coagulation (DIC)
 Methyldopa (aldomet) is
capable of inducing an - laboratory evaluation:
autoimmune reaction.

LEMMINGS 16
 NORMOCYTIC NORMOCHROMIC ANEMIA
 Hgb: normal to marked
decrease
 PBS: schistocytes
 Haptoglobin: decreased
 Plasma Hgb: increased
 Retic count: increased
 DAT: negative
 D-Dimer: increased
* ACANTHOSIS
 Hereditary abetalipoproteinemia
 End-stage liver disease
 Severe starvation, anorexia
nervosa
* SEVERE HYPOPHOSPHATEMIA
 Intravenous hyperalimentation
lacking phosphorus
supplementation
 Severe starvation
 Alcoholism
 Prolonged therapy with phosphate
-binding antacids.
* WILSON'S DISEASE; COPPER
POISONING
 Due to a mutation in the gene for
a ceruloplasmin, a copper
transport protein.
 Patience accumulate excessive
amounts of copper in their tissues,
particularly in the liver.
 Some patients with wilson's
disease develop and abrupt onset
of hemolysis due to sudden
release of copper from the liver.
* OXIDATIVE DRUGS OR CHEMICALS
 Oxidative drugs and chemicals
may cause hemolysis in people
with apparently normal
erythrocytes, as well as in patients
with g6pd and other enzyme
deficiencies.
 Example include sulfonamides,
phenazopyridine (pyridium),
nitrofurantoin (furadantin),
phenacetin, and cisplatin.
 Chemicals include chlorates,
nitrates, naphthalene (mothballs),
methylene blue, and others.
* OSMOTIC EFFECTS
 Burns over more than 15% of the
body can cause hemolysis.
 It is thought that the direct effect
of the heat causes the red cells to
fragment and burst.
* VENOMS
 Brown recluse spider - contain
enzymes that lies the red cell
membrane
 Snakes (cobras) - rarely cause
lysis in vivo.
* INFECTIONS
 Direct infection of erythrocytes:
malaria, babesiasis, bartonellosis,
trypanosomiasis, clostridium
perfringens septicemia.
 Other: gram-positive and gram-
negative septicemia, leptospirosis,
borrelia, others
LEMMINGS 17
 NORMOCYTIC NORMOCHROMIC ANEMIA
25% will convert to aplastic
anemia.
ACQUIRED HEMOLYTIC ANEMIA
- laboratory evaluation:
- PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA (PNH)  Retic count: increased

 It is an acquired intravascular  RBC acetylcholinesterase:

hemolysis anemia characterized decreased
by the intermittent (paroxysmal)
sleep- associated (nocturnal)  WBC, RBC, and platelet count:
blood in the urine (hemoglobinuria) decreased

 Marchiafava - Micheli Syndrome  Urine hemoglobin: positive in first

- cause:
 It is a rare, acquired, clonal
disorder of marrow stem cells in
which there is a deficiency
synthesis of the
glycosylphosphatidylinositol (GPI)
anchor, a structure that attaches
several surface protein to the cell
membrane.
 It results from mutations in the x
chromosome gene coding for
phosphatidylinositol glycan protein
A (PIG-A) which is essential in the
formation GPI anchor.
morning urine
 Screening test: sugar water test
(sucrose hemolysis test): positive
 Confirmatory test: acidified serum
lysis test: (Ham's test) positive
 BM biopsy and aspirate: erythroid
hyperplasia
- therapy:
a. Anemia: iron therapy or
transfusion if severe enough
b. Hemolytic episodes: corticosteroid
therapy to stimulate erythropoiesis

 The lack of surface molecules c. Thromboses: anticoagulant

decay-activating factor (DAF, therapy
CD55) and membrane inhibitor of
reactive lysis (MIRL, CD59) render
red cell sensitivity to lysis b
complement and the result is
chronic intravascular hemolysis.

- clinical features:

 Chronic anemia (hgb: normal to

<6 g/dl)

 Infections

 Thrombosis

 5-10% of cases will convert to

acute myelogenous leukemia;

LEMMINGS 18