Transcript Presentation

Clinical Pathology
Haematology Case E
Ainsley McDonald
Veronica Nou
Poonam Shrestha
Mary Tormey
Ms SP, aged 25, has been taking
clozapine for 6 months.
What is agranulocytosis?
Explain what haematological parameters
must a pharmacist sight before dispensing
clozapine.
What other haematological ADRs are
associated with clozapine?
Explain whether the same monitoring is
required for olanzapine.
What Is Agranulocytosis?
A condition in which there is an insufficient
number of white blood cells called neutrophils or
granulocytes.
This can be caused by
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a failure of the bone marrow to make sufficient
neutrophils or
when white blood cells are destroyed faster than they
can be produced.
Granulocytopenia; Granulopenia; Neutropenia
Granulocytes are a type of white blood
cell. When they are examined under a
microscope, they appear to contain
granules, or small dark specks.
Neutrophils, basophils, and eosinophils
are all types of granulocytes.
These cells are important in the immune
system meaning affected people are more
susceptible to infections.
What is going on in the body?
The bone marrow contains special cells known
as stem cells.
Stem cells may develop into red blood cells,
white blood cells, and platelets.
Certain conditions can damage stem cells, or
change their environment causing them to stop
production.
This may cause a low level of granulocytes in
the body or agranulocytosis.
What are the signs and
symptoms of the condition?
Someone who has agranulocytosis may develop
life-threatening or chronic infections.
Symptoms vary, depending on the type of
infection, but may include the following:
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Chills
Fever
Sore throat
Ulcers in the mouth, stomach or bowels
Weakness
What are the causes and risks of
the condition?
Agranulocytosis can be caused by a number of
factors, including:
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Autoimmune disorders, or conditions in which the
body attacks its own tissues
Chemotherapy
diseases that damage the bone marrow
hereditary disorders
radiation therapy
Certain medications, such as clozapine or
carbamazepine
How is the condition diagnosed?
Diagnosis is usually conducted using a complete
blood count, or CBC, to measure the level of
neutrophils, basophils, and eosinophils.
Genetic testing may be done if heredity is
suspected to be the cause.
If blood tests are abnormal, the provider may
order a bone marrow biopsy. This test involves
inserting a special needle into the hip bone. A
sample is taken from the bone marrow.
What are the long-term effects of
the condition?
Agranulocytosis increases a person's risk for
infections. If white blood cell levels are extremely
low, serious bacterial infections can occur.
Can include infections caused by bacteria that
usually don't cause any problems in the body.
Infection in the bloodstream, known as sepsis,
may lead to life-threatening septic shock.
Increased risk for chronic infections. These can
cause organ damage and scarring.
What are the treatments for the
condition?
Initial treatment of agranulocytosis often includes the
following:
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antibiotics to treat or prevent infections
isolation to keep the person from contracting an infection
stopping the medication that is suspected as the cause of the
agranulocytosis, which may resolve the problem
Other treatments may be ordered, depending on the
cause of the agranulocytosis. These treatments include:
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bone marrow transplant
granulocyte-colony-stimulating factors, such as GM-CSFs or GCSFs, which stimulate the production of granulocytes
matched stem cell transfusions, which replace damaged stem
cells
Bone marrow transplant is an effective treatment
for some people with agranulocytosis.
More than half of good candidates for bone
marrow transplant are cured.
People are good candidates if they meet these
criteria:
under the age of 40 years.
good health prior to the transplant.
matched donor, such as a family member.
What happens after treatment for
the condition?
Until blood cell counts return to normal,
someone who has agranulocytosis is at
risk for infection.
Important to avoid risk factors, such as the
following:
activities that cause a rapid heartbeat, chest pain,
or shortness of breath
excessive exercise
exposure to contagious diseases
Clozapine
What is Clozapine?
Atypical Anti-psychotic.
Used in the treatment of Schizophrenia in
patients who have had an inadequate
response to at least two other antipsychotics, or who cannot tolerate the side
effects of these.
Warning!
Clozpine can cause agranulocytosis.
(Usually reversible on withdrawal of the
drug, although can be fatal)
Only patients that have an initial leucocyte
count (WBC > 3500mm3 and normal
differential blood count) can commence
treatment.
This blood test must be performed 10 days
prior to starting treatment.
Monitoring
Regular WBC counts and absolute
neutrophil counts:
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Weekly during the first 18 weeks
At least monthly thereafter
AND for 1 month after complete
discontinuation of treatment.
Monitoring (2)
At each check-up flu- like symptoms
should be reported (fever, sore- throat) as
could be a sign of neutropenia.
An immediate differential blood count must
be performed if patient shows signs of
illness.
HAEMATOLOGICAL
ADRs ASSOCIATED
WITH CLOZAPINE
Haematological ADRs
associated with Clozapine
Granulocytopenia and Agranulocytosis
Granulocytopenia is defined as a
reduced number of blood granulocytes,
namely neutrophils, eosinophils, and
basophils
Agranulocytosis can prove fatal
Occur within the first 18 weeks of
treatment
Withdrawal of the drug is required
Haematological ADRs
associated with Clozapine
Leucocytosis and Eosinophilia
in the initial weeks of treatment
Discontinuation of therapy may be
warranted in the event of eosinophilia
Discontinue Clozapine if the eosinophil
count rises above 3,000/mm3, and to
restart therapy only after the eosinophil
count has fallen below 1,000/mm3
Haematological ADRs
associated with Clozapine
Thrombocytopenia has been reported
rarely
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reduction in the number of platelets in the
blood
results in bleeding into the skin, spontaneous
bruising , and prolonged bleeding after injury
recommended to discontinue Clozapine if the
platelet count falls below 50,000/mm3
Explain whether
the same
monitoring is
required for
olanzapine.
olanzapine
Also an atypical antipsychotic - but of
lower efficacy than clozapine
Not associated with agranulocytosis,
whereas clozapine has a 1% incidence
(TG-P p2)
The only common hematological
disturbance associated with olanzapine
in clinical trials was eosinophilia (eMims2003)
Rare adverse effect neutropenia (AMH 2003),
whereas clozapine has a 2-3 %
olanzapine
Post Marketing surveillance::(APPG 2002)
Hematological adverse effects:
Leucopenia - rare (0.1-0.01%)
Thrombocytopenia - very rare (<0.01%)
olanzapine
Hyperglyceamia may occur in patients
who had random BGL at the upper limit of
normal Check glucose tolerance in patients who
gain weight
Increased risk of developing type 2
diabetes while taking olanzapine
olanzapine
For all antipsychotics::(AMH 2003 p669)
Routine FBCs & LFTs are advisable,
particularly during the first few months of
treatment and are mandatory with
clozapine
Monitor weight gain, blood glucose &
cholesterol