CASE

STUDY
Oleh: dr. Sri Marwanta SpPD FINASIM
Workshop : CITP
Managemen of Ideopatic Trombcytopenic
Purpura
Hotel Aston - SURAKARTA

This information is for internal educational use only and should not be shown to, discussed with, or left
with anyone outside of Novartis. Use in countries must be approved by local legal/regulatory committee.
Sesi Interaktif
• Test akan dilakukan secara interaktif dengan
menggunakan voting pad
• Voting pad tersedia di meja masing-masing
peserta
• Tentukan pilihan jawaban setelah timer
berjalan dengan menekan 1 kali tombol angka
pilihan yang anda anggap paling benar
• Di larang mencopot/ memindahkan
voting pad dari tempat awal
 3
Pertanyaan percobaan
Gunung yang terkenal di Pulau Lombok?

A. Gunung Semeru 1 0.0%

B. Gunung Tangkuban Perahu2 50.0%

C. Gunung Agung 3 50.0%

D. Gunung Rinjani 4 0.0%

E. Gunung Gede 5 0.0%

CASE #1
A 29-year old woman come to the clinic with bruises and
spots on her arms and legs since 1 month before she come
to the clinic. She also had gum bleeding especially when
she brush her teeth. On physical examination, gingiva
bleeding, hematoma and ptekie in the upper and lower
extremities and abdomen are obtained. No hepatic and lien
enlargement. Laboratory findings : Hemoglobin 13.0 g / dL;
Leucocytes 7800 / uL; Hematocrit 26%; Platelets 10.000 /
uL; Reticulocyte 2.45%; Erythrocyte 3.4 jt / uL; Total
bilirubin 1.0 mg / dL; Conjugated bilirubin 0.4 mg / dL;
Unconjugated bilirubin 0.6 mg / dL.
According to the clinical assesment, what is the most 3
likely diagnosis ?

A. Evans syndrome 1 0.0%

B. Dengue Hemorrhagic Fever

2 50.0%

C. Myelodysplasia syndrome (MDS)

3 50.0%
D. Systemic lupus erythematosus (SLE)

E. Immune thrombocytopenic purpura (ITP) 4 0.0%

5 0.0%
 9
What is the pathophysiology of this clinical condition ?

A. Decreasing formation of platelet

membrane antigens such as GPIIb/IIIa 1 0.0%

B. Megakaryocytes coated with

lymphocyte bind to Fc portion of 2 0.0%

macrophages in spleen and other RES

C. The release of tissue thromboplastin r
thromboplastic substances into the 3 0.0%
circulation
D. Lack of compensatory response by
megakaryocytes due to suppressive 4 0.0%
effect of antiplatelet antibodies
E. Activation of coagulation and
consumption of platelets and 5 0.0%
coagulation products
CASE #2

• A 69-year-old male patient with a personal history

of hypertension, type 2 diabetes, and he was
diagnosed with a Rai 0 stage CLL
• in November 2008, and remained stable without
treatment until 2016
• In June 2016, the patient developed B symptoms
and a CT scan revealed multiple abdominal
lymphadenopathy and splenomegaly (17 cm),
due to disease progression (Rai IV stage)
• From the Complete Blood count we found Hb
9.95 g/dl, platelets 91.4 × 109/L, and WBC 124 ×
109/L (90% lymphocytes)
• A bone marrow biopsy
was performed; the
report described areas
of moderate infiltration
by small and mature
lymphocytes cells, with
conserved numbers of
megakaryocytes of
heterogeneous aspect.
What is the diagnosis of this patient? 2

A. autoimmune hemolytic 1 50.0%

anemia (AIHA)
B. CLL and immune 2 50.0%

thrombocytopenia (ITP)
C. CLL and pure red cell 3 0.0%

aplasia (PRCA)
D. CLL and autoimmune 4 0.0%

granulocytopenia (AIG)
E. CLL and CML 5 0.0%
Discussion …

• The second most common among

autoimmune disorder associated with CLL is
immune thrombocytopenic purpura (ITP), with
an incidence of approximately 2–5% of the
CLL population.
• The ITP physiopathology is characterized by
increased destruction and impaired production
of platelets caused by autoantibodies directed
against the platelets and megakaryocytes,
making ITP diagnosis a clinical challenge
• The patient commenced oral prednisone at a
dose of 1mg/kg in three consecutive days.
• The platelet count remained < 40 × 109/L despite
the treatment but without signs of bleeding.
• In October 2016, the patient required
hospitalization due to symptoms and signs of
congestive cardiac failure, with left ventricular
ejection fraction of 25% by echocardiogram in
addition to dilated myocardiopathy signs.
• Anticoagulant therapy for thromboembolic risk
prevention was proposed, which could not be
initiated because the patient’s platelet count
was below 50 × 109/l with Hb 12,8 g/dl, WBC
9.11 × 109/L, and neutrophils 7.8 × 109/L.
 2
What medication we choose to increase the
level of thrombocyte in this patient?
A. Watch full waiting 1 0.0%

B. Platelet 2 50.0%

transfusion
C. Apheresis 3 0.0%

transfusion
D. Eltrombopag 4 0.0%

E. Prednisone 5 50.0%
discussion
CASE #3
• A 43-year-old female was diagnosed with ITP 6 years ago during pregnancy
(male fetus) and had been treated with steroids.
• Over the years, she underwent a number of treatments for “refractory” ITP
including, in addition to corticosteroids, splenectomy, rituximab, cyclosporine,
azathioprine, vincristine, and mycophenolate mofetil
 9
What is the next chosen treatment for
this patient?
A. high-dose 1 0.0%
cyclophosphamide added
with Eltrombopag
B. Plasmapheresis 2 0.0%

3 0.0%
C. repeat corticosteroids again

4 0.0%
D. Dapsone
5 0.0%

E. All above are correct

Discussion…
• HD cyclophosphamide has also been described for
the treatment of refractory ITP.
• Eltrombopag is an FDA approved thrombopoietin
receptor agonist for the treatment of patients with
chronic ITP.
• A rare patient will undergo hematopoietic stem cell
transplantation for refractory ITP. High-dose (HD)
cyclophosphamide given over multiple days as
used for conditioning before allogeneic stem cell
transplantation and for graft versus host disease
prophylaxis is profoundly immunosuppressive.
 10

What is mechanism of action of eltrombopag?

A. a sulfone active to induced 1 0.0%

thrombocyte maturation

B. depleting guanosine nucleotides to 2 0.0%

increased the thrombocyte
C. TPO receptor agonist to initiates
signaling cascades that induced 3 0.0%
proliferation and differentiation of
megakaryocytes
D. suppresses glycosylation to 4 0.0%

increased thrombocyte level

5 0.0%
E. depletes tetrahydrobiopterin to
increased formation of thrombocyte
Case #4

• A 19 year old boy presented with complaints of

petechaeal rash over body for five days and
bleeding from nose for two days.
• No history of fever or pallor was elicited. Nose
bleed comprised only 5 to 6 drops of fresh blood
and subsided spontaneously or with local
pressure.
• On examination, petechiae and purpura were
present over the trunk, extremities, face and oral
mucosa. There was no organomegaly and
lympadenopathy. His vitals were stable and blood
pressure was within normal range for the age.
• On laboratory investigations hemoglobin was 11,
total leukocyte count was 9.25 x 109/L and
platelet count was 11.2 x 109/L. Renal function
test, liver function test and coagulation profile
were within normal limits.
• Antinuclear antibody and serology for HIV and
hepatitis B surface antigen were negative
Picture of patient
What is the next step examination do you want to do 8
to make a diagnosis?

A. Hb electrophoresis
1 0.0%

B. Bone Marrow Puncture 2 0.0%

C. Protein electrophoresis 3 0.0%

4 0.0%
D. Bone Scan

5 0.0%

E. Coomb Test
• Bone marrow biopsy
was done before
starting treatment.
Bone marrow
examination showed
increased number of
megakarocytes without
any other abnormality.
 9
What is your diagnosis of this patient?

A. Multiple Myeloma 1 0.0%

B. AIHA 2 0.0%

C. ITP 3 0.0%

D. CML 4 0.0%

E. AML 5 0.0%
 8
What are the first line therapy of this patient?
A. TPO-RA
1 0.0%

B. Corticosteroid
2 0.0%

C. IVIg
3 0.0%

D. Anti-D
4 0.0%

E. option B,C and D are correct

5 0.0%
After give the first line therapy, thrombocyte 9
level are still low, and there are no response
from this patient. What next step we do for the
second line therapy?
A. watchful waiting 1 0.0%

B. Spleenectomy 2 0.0%

C. Rituximab 3 0.0%

D. eltrombopag (TPO-RA) 4 0.0%

E. option B,C and D are correct 5 0.0%

discussion
Case #5

• A 27-year-old multigravida, a known case of ITP,

was referred to the Department of Obstetrics and
Gynecology at 26 weeks of gestation with
complaints of spotting per vagina and petechial
spots over her face and limbs.
• She was a fifth gravida with a bad obstetric
history of three abortions and one neonatal
death.
• Diagnosis of ITP was made after her second
pregnancy and treatment was started with
steroids and immunosuppressant. Splenectomy
was advised but she refused due to fear of
surgery.
• She was given platelet transfusions three times in
the current pregnancy before she was admitted to
our hospital. She was on azathioprine 50 mg and
prednisolone 40 mg daily since 2 months. Her
platelet count was 10,000/µl at the time of
admission. She was transfused with four units of
platelets.
• Laboratory investigations for antinuclear antibody,
beta 2 microglobulin, lupus anticoagulant,
anticardiolipin antibodies were negative and all
other causes of recurrent abortion were ruled out.
All other blood investigations were normal except
for a prolonged bleeding time
• Due to high costs, short action periods, and other
potential maternal side-effects of IVIgG and anti-
D, it was decided that TPO-mimetic drug
eltrombopag would be given at 29 weeks of
gestation
 9
Which one is the dose of eltrombopag do
you choose?
A. 25 mg once daily (OD) was given for
7 days. The dose was then increased 1 0.0%

to 50 mg
B. 250 mg once daily (OD) was given
2 0.0%
for 7 days. The dose was then
increased to 500 mg
C. 2.5 mg once daily (OD) was given for 3 0.0%
7 days. The dose was then increased
to 5 mg
D. 0. 25 mg once daily (OD) was given 4 0.0%
for 7 days. The dose was then
increased to 0.5 mg
E. All correct 5 0.0%
Discussion…

• Eltrombopag is initiated with 50 mg OD dose

for most patients with chronic ITP. The initial
dose can be reduced in patients with hepatic
impairment. The dose can be adjusted to
maintain a platelet count of ≥50 × 109/L. Daily
doses should not exceed 75 mg.
• A 25 mg OD dose was tried for our patient due
to cost constraints and considering pregnancy
but the dose was changed to 50 mg OD as we
failed to achieve a rise in platelet count as
expected.
• After starting treatment with eltrombopag, her
platelet count never went below 30,000/µl and
she had no signs and symptoms of bleeding.
Platelet transfusion was not given to the patient
till delivery after the commencement of treatment
with eltrombopag.
 9
What kind of drug is eltrombopag?

A. Tyrosine Kinase Inhibitor 1 0.0%

B. Proton Pump Inhibitor 2 0.0%

C. Alkylating Agent 3 0.0%

D. Thrombopoietin Receptor4 0.0%

Agonist
E. Sulfone active
5 0.0%
• Eltrombopag has been assigned to pregnancy
category C by the Food and Drug Administration
(FDA). There are no adequate and well-
controlled studies of eltrombopag use in
pregnancy. Eltrombopag should be used in
pregnancy only when benefit outweighs risk.
 7
What are the side effect of eltrombopag
in pregnancy?
A. embryo lethality and 1 0.0%
reduced fetal weights
B. Placenta previa 2 0.0%

C. IUGR 3 0.0%

D. Severe Preeclamsia 4 0.0%

E. Diabetes gestasional 5 0.0%

discussion

• Eltrombopag should be used in pregnancy only

when benefit outweighs risk.
• In animal reproduction and developmental
toxicity studies, there was evidence of embryo
lethality and reduced fetal weights at maternally
toxic doses.
• In our case, the drug was started during the third
trimester and so there was no question of embryo
lethality.
 9
What are the common adverse reactions
for eltrombopag ?

A. nausea and vomiting 1 0.0%

B. Diarrhea 2 0.0%

C. Myalgia 3 0.0%

D. oropharyngeal pain and 4 0.0%

pharyngitis
E. All correct 5 0.0%
Discussion …

• The most common adverse reactions include

nausea, diarrhea, upper respiratory tract
infection, vomiting, myalgia, urinary tract
infection, oropharyngeal pain, pharyngitis, back
pain, influenza, paresthesia, and rash
 7
The most important complication
of eltrombopag is?

A. Nephrotoxicity 1 0.0%

B. Hepatotoxicity 2 0.0%

C. Neurotoxicity 3 0.0%

D. Ototoxicity 4 0.0%

E. Ophalmotoxicity 5 0.0%
Discussion…

• The most important complication of this drug is

hepatotoxicity and so the monitoring of liver
function before and during therapy is very
essential.
• For our patient, liver function tests were
performed before starting therapy with
eltrombopag and it was repeated every 2 weeks
and before discharge from hospital
Thank You