Transcript 35371

Hemolytic
anemia
Rakesh Biswas
MD, Professor, Department of Medicine,
People's College of Medical Sciences,
Bhanpur, Bhopal, India
Young man of 19
Complains of giddiness
weakness, pallor
Examination reveals a spleen
mild lemon yellow sclera
How shall you investigate to find
out the cause of the problem?
Laboratory investigations:
Severe normochromic, normocytic
anemia (hemoglobin level of 6.4 g/dL
Reticulocyte count of 12.2%.
Blood film:
Bilirubin level of 2.5 mg/dL,
Lactate dehydrogenase (LDH) of
2140 IU/L,
Haptoglobin below 7 mg/dL
Introduction
Mean life span of a RBC-120days
 Removed Extravascularly by- Macrophages
of RE system

Hemolytic Anemia

Definition:


Those anemias which result from an increase
in RBC destruction
Classification:
Congenital / Hereditary
 Acquired

Laboratory Evaluation of Hemolysis
Extravascular Intravascular
HEMATOLOGIC
Routine blood film
Reticulocyte count
Bone marrow
examination
Polychromatophilia
Polychromatophilia
Erythroid
hyperplasia
Erythroid
hyperplasia
PLASMA OR SERUM
Bilirubin
Haptoglobin
Plasma hemoglobin
Lactate dehydrogenase
Unconjugated
, Absent
N/
(Variable)
Unconjugated
Absent
(Variable)
URINE
Bilirubin
Hemosiderin
Hemoglobin
0
0
0
0
+
+ severe cases
Hemoglobinuria
Classification of Hemolytic Anemias
Hereditary
1. Abnormalities of RBC interior
a.Enzyme defects: G-6-PD def,PK def
b.Hemoglobinopathies
2. RBC membrane abnormalities
a. Hereditary spherocytosis etc.
b. PNH
Acquired
c. Spur cell anemia
3. Extrinsic factors
a. Hypersplenism
b. Antibody: immune hemolysis
c. Mechanical trauma: MAHA
d. Infections, toxins, etc
Ref : Harrison’s
Features of HEMOLYSIS
Bilirubin
LDH
Reticulocytes, n-RBC
Haptoglobulins
+ve Urinary hemosiderin, Urobilinogen
Blood Film
Spherocytes
DCT +ve
AI Hemolysis
No spherocytes
Fragmentation
DCT –ve
H. Sherocytosis
Malaria,
Clostidium
Hereditery enzymopathies Microangiopathic,
Traumatic
Red Cell Membrane Defects
1.Hereditary Spherocytosis
Usually inherited as AD disorder
 Defect: Deficiency of Beta Spectrin or Ankyrin
 Loss of membrane in Spleen & RES
becomes more spherical Destruction in
Spleen

RBC Membrane
 C/F:
Asymptomatic
Fluctuating
hemolysis
Splenomegaly
Pigmented gall stones- 50%
Complications

Clinical course may be complicated with
Crisis:
Hemolytic Crisis: associated with infection
 Aplastic crisis: associated with Parvovirus
infection
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
Inv:
Test will confirm Hemolysis
 P Smear: Spherocytes
 Osmotic Fragility: Increased

Screen Family members
Osmotic Fragility

Management:
Folic Acid 5mg weekly, prophylaxis life long
 Spleenectomy
 Blood transfusion in Ac, severe hemolytic crisis

2.Hereditary Elliptocytosis
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Equatorial Africa, SE Asia
AD / AR
Functional abnormality in one or more anchor
proteins in RBC membrane- Alpha spectrin ,
Protein 4.1
Usually asymptomatic
Mx: Similar to H. spherocytosis
Variant:
3.SE-Asian ovalocytosis:
 Common in Malaysia , Indonesia…
 Asymptomatic-usually
 Cells oval , rigid ,resist invasion by malarial
parasites
Elliptocytosis
Red Cell Enzymopathies

Physiology:
EM pathway: ATP production
 HMP shunt pathway: NADPH & Glutathione
production

1. Glucose-6-Phosphate Dehydrogenase
( G6PD ) Deficiency
 Pivotal
enzyme in HMP Shunt & produces
NADPH to protect RBC against oxidative
stress
 Most
common enzymopathy -10%
world’s population
 Protection against Malaria
 X-linked
(Reduced form)
(Oxidised form)

Clinical Features:

Acute drug induced hemolysis:
 Aspirin,
primaquine, quinine, chloroquine,
dapsone….
Chronic compensated hemolysis
 Infection/acute illness
 Neonatal jaundice
 Favism

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Inv:
 e/o non-spherocytic intravascular
hemolyis
 P. Smear: Bite cells, blister cells,
irregular small cells, Heinz bodies,
polychromasia
 G-6-PD level

Treatment:
 Stop the precipitating drug or treat the
infection
 Acute transfusions if required
2. Pyruvate Kinase Deficiency
 AR
 Deficient
ATP production, Chronic
hemolytic anemia
 Inv;
P. Smear: Prickle cells
Decreased enzyme activity
 Treatment:
Transfusion may be required
Hemolobinopathies…
Autoimmune Hemolytic Anemia
Result from RBC destruction due to RBC
autoantibodies: Ig G, M, E, A
 Most commonly-idiopathic
 Classification

Warm AI hemolysis:Ab binds at 37degree
Celsius
 Cold AI Hemolysis: Ab binds at 4 degree
Celsius
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1.Warm AI Hemolysis:
Can occurs at all age groups
F>M
 Causes:
 50% Idiopathic
 Rest - secondary causes:
1.Lymphoid neoplasm: CLL, Lymphoma,
Myeloma
2.Solid Tumors: Lung, Colon, Kidney, Ovary,
Thymoma
3.CTD: SLE,RA
4.Drugs: Alpha methyl DOPA, Penicillin ,
Quinine, Chloroquine
5.Misc: UC, HIV

MACROCYTE
SPHEROCYTE
IMMUNOHEMOLYTIC ANEMIA
complement
Direct antiglobulin test
demonstrating the presence of autoantibodies (shown
here) or complement on the surface of the red blood
cell.

Inv:
e/o hemolysis, MCV
 P Smear: Microspherocytosis, n-RBC
 Confirmation: Coomb’s Test / Antiglobulin test
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Treatment
Correct the underlying cause
 Prednisolone 1mg/kg po until Hb reaches
10mg/dl then taper slowly and stop
 Transfusion: for life threatening problems
 If no response to steroids  Spleenectomy or,
 Immunosuppressive: Azathioprine,
Cyclophosphamide

2. Cold AI Hemolysis
 Usually Ig M
 Acute or Chronic form
 Chronic:
 C/F:
 Elderly
patients
 Cold , painful & often blue fingers, toes,
ears, or nose ( Acrocyanosis)

Inv:
e/o hemolysis
 P Smear: Microspherocytosis
 Ig M with specificity to I or I Ag
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Other causes of Cold Agglutination:
Infection: Mycoplasma pneumonia, Infec
Mononucleosis
 PCH : Rare cause seen in children in
association with cong syphilis


Treatment:
Treatment of the underlying cause
 Keep extremities warm
 Steroids treatment
 Blood transfusion
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Non-Immune Acquired Hemolytic
Anemia
1. Mechanical Trauma
A). Mechanical heart valves, Arterial grafts:
cause shear stress damage
B).March hemoglobinuria: Red cell damage in
capillaries of feet
C). Thermal injury: burns
D). Microangiopathic hemolytic anemia (MAHA):
by passage of RBC through fibrin strands
deposited in small vessels  disruption of
RBC eg: DIC,PIH, Malignant HTN,TTP,HUS
TRAUMATIC HEMOLYSIS
Acquired hemolysis
2.Infection
F. malaria: intravascular hemolysis: severe
called ‘Blackwater fever’
Cl. perfringens septicemia
3.Chemical/Drugs: oxidant denaturation of
hemoglobin
Eg: Dapsone, sulphasalazine, Arsenic
gas, Cu, Nitrates & Nitrobenzene
The direct antiglobulin test was
positive for complement (C3d) (++),
and IgG (++-).
Also was positive for agglutinins of
IgM type and had a titer of 1:1024.
Serologies for human
immunodeficiency virus, hepatitis B
and C viruses, and Mycoplasma
pneumoniae were negative.
Rheumatoid factor and antinuclear
antibodies were undetectable.
Prednisone therapy was started at
a dose of 1 mg/kg intravenously,
daily. Hemoglobin level rose to
11 g/dL, concomitantly with the
improvement of hemolytic signs.
A reduction of positivity of both
direct and indirect antiglobulin tests
(polyvalent serum + ; C3d + ;
IgG+ ), as well as a reduction of
cold agglutinin titers (1:128), was
observed 8 weeks after
corticosteroid therapy.
Three months later, corticosteroids
were tapered to a maintenance
dose of 25 mg daily.
Hemolysis recurred again with the
fall of hemoglobin to 7 g/dL.
The direct antiglobulin test recurred
positive for polyvalent serum (+++),
complement (+++), and IgG (+++),
while cold agglutinin titers again
became strongly positive (1:256).
Immunophenotyping of bone
marrow cells showed that 10% of
all the cells were CD20 and CD19
positive.
CD20 is widely expressed on Bcells.
CD20 could play a role in Ca2+
influx across plasma membranes,
maintaining intracellular Ca2+
concentration and allowing
activation of B cells.
Rituximab is a monoclonal
antibody that binds to CD 20
Rituximab was started at the dose
of 375 mg/mq once weekly, for a
total of 4 doses
Hemoglobin value reached
13.5 g/dL just before the third dose,
although biochemical signs of
hemolysis remained substantially
unaltered.
At the end of therapy, the hemolytic
signs disappeared, the direct and
indirect antiglobulin tests became
negative, and cold agglutinin titers
fell to 1:32
Immunophenotyping of bone
marrow cells showed the absence
of CD20 and CD19 B cells.
Summary of lecture
Learning points