Transcript HEMOLYTIC ANEMIA

Dr. M. A Sofi
MD; FRCP (London); FRCEdin; FRCSEdin
HEMOLYTIC ANEMIA
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Hemolysis is the premature destruction of
erythrocytes.
A hemolytic anemia will develop if bone marrow
activity cannot compensate for the erythrocyte loss.
The severity of the anemia depends on whether the
onset of hemolysis is gradual or abrupt and on the
extent of erythrocyte destruction.
Mild hemolysis can be asymptomatic while
the anemia in severe hemolysis can be life
threatening and cause angina and cardiopulmonary
decompensation.
HEMOLYTIC ANEMIA
Hemolytic anemia is a form of anemia due to
hemolysis, the abnormal breakdown of red blood
cells (RBCs), either in the blood vessels
(intravascular hemolysis) or elsewhere in the
human body (extravascular).
 It has numerous possible causes, ranging from
relatively harmless to life-threatening.
 The general classification of hemolytic anemia is
either inherited or acquired.
 Treatment depends on the cause and nature of the
breakdown.
HEMOLYTIC ANEMIA
Hemolytic anemia involves:
 Abnormal and accelerated
destruction of red cells.
 Increased breakdown of
hemoglobin, which may
result in:
 Increased bilirubin level
(mainly indirect-reacting)
with jaundice
 Increased fecal and urinary
urobilinogen
 Hemoglobinemia,
methemalbuminemia,
hemoglobinuria and
hemosiderinuria
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Bone marrow compensatory
reaction:
Erythroid hyperplasia with
accelerated production of red
cells, reticulocytosis, and
slight macrocytosis.
Expansion of bone marrow in
infants and children with
severe chronic hemolysis changes in bone visible on Xray
The balance between red cell
destruction and marrow
compensation determines the
severity of anemias.
HEMOLYTIC ANEMIA
Pathogenesis
 Normal red cells have a
lifespan of about 120
days. The lifespan may be
very short in haemolytic
anaemia (eg as short as
five days in sickle cell
anemia).
Hemolysis may occur by
two mechanisms:
Intravascular:
 Complement fixation
 Trauma
Extravascular: most
common:
 Red cells are removed from
the circulation by the
mononuclear-phagocytic
system either because they
are intrinsically defective or
because of the presence of
bound immunoglobulins to
their surfaces.
Causes extravascular hemolysis in the adult
Intrinsic red blood cell
defects
 Enzyme deficiencies (e.g.,
G6PD or pyruvate kinase
deficiencies)
 Hemoglobinopathies (e.g.,
sickle cell disease,
thalassemias, unstable
hemoglobins)
 Membrane defects (e.g.,
hereditary spherocytosis,
elliptocytosis)
Extrinsic red blood cell
defects
 Liver disease
 Hypersplenism
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Infections (e.g., bartonella,
babesia, malaria)Oxidant
agents (eg, dapsone, nitrites,
aniline dyes)
Other agents (e.g., lead,
copper, snake and spider
bites)
Large granular lymphocyte
leukemia
Autoimmune hemolytic
anemia (warm- or coldreacting, drugs)
Intravenous immune globulin
infusion
Causes intravascular hemolysis in the adult
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Microangiopathic hemolytic anemia (e.g., TTP, HUS, aortic
stenosis, prosthetic valve leak)
Transfusion reactions (e.g., ABO incompatibility)
Infection (e.g., clostridial sepsis, severe malaria)
Paroxysmal cold hemoglobinuria; cold agglutinin disease
Paroxysmal nocturnal hemoglobinuria
Following intravenous infusion of Rho(D) immune globulin
Following intravenous infusion with hypotonic solutions
Snake bites
Exposure to compounds with high oxidant potential (e.g.,
copper poisoning, Wilson disease)
HEMOLYTIC ANEMIA: Etiology
Intrinsic causes:
Red cell membrane
abnormalities:
 Hereditary spherocytosis,
 Elliptocytosis.
Hemoglobin
abnormalities:
 Sickle cell anemia,
 Thalassemia.
 Congenital
dyserythropoietic anemia
Enzyme defects:
 Glucose-6-phosphate
dehydrogenase (G6PD),
 Pyruvate kinase deficiency
HEMOLYTIC ANEMIA: Etiology
Extrinsic causes
 Acquired hemolytic anemia
may be caused by immunemediated causes, drugs and
other miscellaneous causes.
 Immune-mediated causes
could include transient
factors as in Mycoplasma
pneumoniae infection (cold
agglutinin disease)
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Permanent factors as in
autoimmune diseases like
autoimmune hemolytic
anemi (itself more
common in diseases such
as systemic
lupus erythematosus,
Rheumatoid arthritis,
Hodgkin's lymphoma
Chronic lymphocytic
leukemia.
HEMOLYTIC ANEMIA: Etiology
Extrinsic:
 Paroxysmal nocturnal
hemoglobinuria (PNH), is a
rare, acquired, potentially
life-threatening disease of
the blood characterized by
complement-induced
intravascular hemolytic
anemia.
 Any of the causes of
hypersplenism (increased
activity of the spleen), such
as portal hypertension
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Acquired hemolytic anemia
in burns and as a result of
infections.
Lead poisoning causes nonimmune hemolytic anemia.
Runners can suffer
hemolytic anemia due to
"footstrike hemolysis",
destruction of red blood
cells in feet at foot impact.
Low-grade hemolytic
anemia occurs in 70% of
prosthetic heart valve
recipients, and severe
hemolytic anemia occurs in
3%
HEMOLYTIC ANEMIA:
Peripheral blood smear with
sickled cells
Thalassemia marked
microcytosis (M) and
anisopoikilocytosis (P) than in
thalassemia minor. Target
cells (T) and hypochromia are
prominent.
HEMOLYTIC ANEMIA
The direct antiglobulin (Coombs) test
is used to determine whether RBCbinding antibody (IgG) or complement
(C3) is present on RBC membranes. The
patient's RBCs are incubated with
antibodies to human IgG and C3. If IgG
or C3 is bound to RBC membranes,
agglutination occurs–a positive result.
The indirect antiglobulin (Coombs) test
is used to detect IgG antibodies against
RBCs in a patient's serum. The patient's
serum is incubated with reagent RBCs; then
Coombs serum (antibodies to human IgG,
or human anti-IgG) is added. If
agglutination occurs, IgG antibodies
(autoantibodies or alloantibodies) against
RBCs are present.
HEMOLYTIC ANEMIA
Epidemiology
 Risk factors are variable and depend on the underlying
cause.
 Sickle cell disorders mainly affect Africans and Arabs.
 Glucose-6-phosphate dehydrogenase (G6PD) deficiency
has several variants, divided into five classes according to
the level of enzyme activity. These have typical geographic
spread. Common locations are the Middle East and the
Mediterranean.
 Autoimmune haemolytic anaemia is slightly more
common in females than in males. Most often, it presents
in middle-aged and older individuals.
HEMOLYTIC ANEMIA
Symptoms
 Symptoms are due to both
anemia and the underlying
disorder.
 Patients with minimal longstanding haemolytic anemia
can be asymptomatic.
 Severe anemia, especially of
sudden onset, may cause
tachycardia, dyspnoea, angina
and weakness.
 Gallstones may cause
abdominal pain.
 Bilirubin stones can develop
in patients with persistent
Haemoglobinuria can occur in
patients with intravascular
haemolysis.
Medication history:
 Some medications, e.g.
penicillin, quinine and Ldopa, may cause immune
haemolysis.
 Oxidant drugs, e.g. nalidixic
acid, (and also fava beans
and infections) can trigger
haemolysis in patients with
glucose-6-phosphate
dehydrogenase (G6PD)
deficiency.
HEMOLYTIC ANEMIA
Signs
Signs of anemia:
 general pallor.
 Tachycardia, tachypnoea
and hypotension.
Mild jaundice may occur due
to haemolysis.
 Splenomegaly: occurs with
some causes, e.g. hereditary
spherocytosis.
 Leg ulcers may occur in
some causes of haemolytic
anemia, e.g. sickle cell
anaemia.
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Right upper abdominal
quadrant tenderness may
indicate gallbladder disease.
Bleeding and petechiae
indicate thrombocytopenia
due to Evans' syndrome or
thrombotic
thrombocytopenic purpura
if neurological signs are also
present.
Signs of underlying disorder,
e.g. malar rash in patients
with SLE.
HEMOLYTIC ANEMIA
Investigations:
 Complete blood cell count
 Peripheral blood smear
 Serum lactate
dehydrogenase (LDH) study
 Serum haptoglobin
 Indirect bilirubin
 Platelet count is normal in
most hemoltic anemias
Thrombocytopenia:
 SLE, Microangiopathic
haemolytic anaemia,TTP,
HUS, DIC.
High MCH and MCHC:
suggest spherocytosis.
Coombs' test:
 Immune-mediated
haemolytic anaemia
(antibody-mediated
destruction of RBCs).
Cold agglutinins:
 Mycoplasma infections and a
 Infectious mononucleosis.
 PNH.
 Ultrasound to estimate
spleen size.
 CXR and ECG: may be
needed to assess
cardiopulmonary status.
HEMOLYTIC ANEMIA
Assess presence of
haemolysis
Red cell destruction:
 Reduced haemoglobin.
 Spherocytes, fragmented
red cells, nucleated red cells
or other abnormal red cells.
 Increased serum
unconjugated bilirubin,
 Increased LDH and
 Reduced or absent
haptoglobin.
Increased urinary
urobilinogen,
haemosiderinuria.
Increased red cell
production:
 Increased reticulocytosis:
may also be due to blood
loss or a bone marrow
response to iron, vitamin B12
or folate deficiencies.
 Increased red cell MCV (due
to reticulocytosis; but there
are many other causes, e.g.
vitamin B12 and folate
deficiency
HEMOLYTIC ANEMIA
Determine haemolysis is
intravascular
 Increased plasma
haemoglobin.
 Methaemoglobinaemia.
 Hemoglobinuria.
Identify the cause
Genetic:
Red cell morphology:
 Spherocytes (suggest
congenital spherocytosis or
autoimmune haemolytic
anaemia),
 Elliptocytes, schistocytes
Screen for sickle cell: sickling
under reduced conditions.
 Hemoglobin electrophoresis.
 Red cell enzyme assays.
Acquired:
Antibodies:
 IgG warm antibodies
 IgM cold antibodies
 The direct antiglobulin test is
positive in autoimmune
haemolytic anaemia.
 Red cell morphology: e.g.
haemolytic uraemic
syndrome, thrombotic
thrombocytopenic purpura.
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HEMOLYTIC ANEMIA
MECHANISM
DISORDER
Disorders Extrinsic to the RBC
Reticuloendothelial hyperactivity
Immunologic abnormalities
Hypersplenism
Autoimmune hemolytic anemias:
•Cold antibody
•Paroxysmal cold hemoglobinuria
•Warm antibody
Infectious organisms
Babesia sp
Bartonella bacilliformis
Plasmodium falciparum
P. malariae
P. vivax
Toxin production by infectious organisms Clostridium perfringens
α- and β-Hemolytic streptococci
Meningococci
Mechanical trauma
March hemoglobinuria
Skeletal trauma
Thrombotic thrombocytopenic purpura and
hemolytic-uremic syndrome
Valvular heart disorders
HEMOLYTIC ANEMIA
MECHANISM
DISORDER
Toxins
Compounds with oxidant potential (e.g., dapsone,
phenazopyridine)
Copper (Wilson disease)
Lead
Insect venom
Snake venom
Intrinsic RBC abnormalities
Congenital RBC membrane disorders Hereditary elliptocytosis
Hereditary spherocytosis
Acquired RBC membrane disorders Hypophosphatemia
Paroxysmal nocturnal hemoglobinuria
Stomatocytosis
Disorders of RBC metabolism
Embden-Meyerhof pathway defects (eg, pyruvate
kinase deficiency)
Hexose monophosphate shunt defects (eg, G6PD
deficiency)
Disorders of Hb synthesis
Hb C disease
Hb S-C disease
Hb E disease
HEMOLYTIC ANEMIA
General measures
 Administer folic acid
because active haemolysis
may cause folate deficiency.
 Discontinue medications
that may have precipitated
or aggravated haemolysis.
Transfusion therapy
 Avoid transfusions unless
absolutely necessary, but
they may be essential.
 In autoimmune haemolytic
anemia, type-matching and
cross-matching may be
difficult.
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Use the least incompatible
blood if transfusions are
indicated.
The risk of acute hemolysis of
transfused blood is high, but
the degree depends on the
rate of infusion.
Iron therapy
 This is indicated for patients
with severe intravascular
hemolysis in which persistent
haemoglobinuria has caused
substantial iron loss
HEMOLYTIC ANEMIA
Splenectomy
 This may be the first choice
of treatment in some types
of haemolytic anaemia such
as hereditary spherocytosis.
 In other cases it is
recommended when other
measures have failed.
 Splenectomy is usually not
recommended in
haemolytic disorders such
as cold agglutinin
haemolytic anaemia.
Complications:
 Anemia may lead to highoutput cardiac failure.
 Jaundice creates problems
associated with increased
unconjugated bilirubin.
 In patients with intravascular
haemolysis, iron deficiency
due to chronic
haemoglobinuria can
exacerbate anemia and
weakness.