TINJAUAN PUSTAKA
antigen virus yang mirip antigen trombosit,
disebut juga molecular mimicry, yang kemudian
meningkatkan autoantibodi antiplatelet.7
Gangguan autoimun dan limfoproliferatif
juga dapat mendasari terjadinya ITP seperti
systemic lupus erythematosus (SLE) dan
leukemia limfositik kronis.5
Gambar. Mekanisme terjadinya ITP primer7,8
A. Sel T diaktivasi saat pengenalan antigen oleh
APC menyebabkan aktivasi sel B. Sel B kemudian
memproduksi autoantibodi yang spesifik untuk
glikoprotein trombosit dan megakariosit.
B. Trombosit yang telah berikatan dengan
autoantibodi kemudian berikatan dengan reseptor
Fc dan terjadi proses fagositosis pada limpa.
C. Autoantibodi juga berikatan dengan megakariosit
sehingga maturasi megakariosit terhambat dan
juga terjadi destruksi megakariosit
KLINIS
Perdarahan merupakan manifestasi klinis
yang paling sering. Perdarahan dapat terjadi
pada mukokutaneus seperti rongga mulut
dan kulit. Perdarahan kulit dapat berupa
purpura tanpa penyebab yang jelas, pada
mukosa dapat berupa mimisan, gusi berdarah,
dan perdarahan saluran gastrointestinal.2
Perdarahan intrakranial dan saluran cerna
sangat jarang namun sangat berbahaya.
Perdarahan intrakranial memiliki insidens
kurang dari 0,2% dan terjadi pada jumlah
trombosit kurang dari 10.000/µL.2,3
Keluhan lain yang sering diabaikan adalah
kelelahan (fatigue). Gejala ini bisa terjadi pada
pasien ITP dengan trombosit di bawah 10.000/
µL, perdarahan, serta terapi steroid. Beberapa
CDK-280/ vol. 46 no. 11 th. 2019
penelitian menyebutkan bahwa rasa lelah
dapat dipengaruhi oleh meningkatnya sitokin
inflamasi seperti IL-2 dan IFN-Ύ.2
Pasien ITP memiliki risiko tromboemboli
disebabkan peningkatan antiphospholipid
antibodies (APLA).2
DIAGNOSIS
Diagnosis melalui beberapa pemeriksaan
dasar seperti anamnesis, pemeriksaan fisik,
pemeriksaan darah tepi, dan pemeriksaan
sumsum tulang belakang. Anamnesis untuk
riwayat keluarga, riwayat perdarahan, riwayat
penyakit sebelumnya, serta penggunaan obat-
obatan. Pemeriksaan fisik lengkap terutama
pada bagian-bagian tubuh yang sering
mengalami perdarahan seperti mukokutan
dan persendian; namun pada sebagian
besar pasien ITP tidak didapati kelainan pada
pemeriksaan fisik.5,9 Pada pasien ITP juga perlu
dicari adanya limfadenopati atau splenomegali
untuk menyingkirkan keganasan seperti
gangguan limfoproliferatif.5 Pada pasien
dewasa perlu dilakukan pemeriksaan HCV dan
HIV untuk menyingkirkan kemungkinan ITP
sekunder.1
Pemeriksaan laboratorium apusan darah
tepi merupakan pemeriksaan sederhana
yang sangat penting. ITP ditandai dengan
menurunnya jumlah trombosit terisolasi
kurang dari 100.000/µL.1 Trombositopenia
terisolasi didefinisikan sebagai
trombositopenia tanpa gangguan morfologi
serta jumlah eritrosit dan leukosit.2,9
Menurut American Society of Hematology,
pemeriksaan sumsum tulang belakang tidak
perlu karena pemeriksaan apusan darah
tepi yang cermat sudah dapat menegakkan
diagnosis ITP.1 Pada pemeriksaan sumsum
tulang belakang, dapat ditemukan jumlah
megakariosit meningkat atau normal, dapat
terjadi peningkatan jumlah megakariosit
imatur.2
TATALAKSANA Wei Y, et al, pengobatan ITP dewasa yang baru
Pasien anak yang baru didiagnosis ITP
dan tidak memiliki gejala perdarahan atau
perdarahan ringan (misalnya perdarahan
kulit) tidak membutuhkan terapi spesifik dan
disarankan istirahat total (bed rest).1,4
Pasien dewasa yang baru terdiagnosis ITP
dengan jumlah trombosit di bawah 30x109/L
membutuhkan terapi walaupun tanpa
perdarahan mukosa.1,4
Angka morbiditas dan mortalitas pasien
dewasa meningkat sehingga membutuhkan
tatalaksana yang lebih kompleks dibandingkan
pasien anak. Hal ini karena banyak pasien ITP
dewasa berkembang menjadi kasus kronis
dan risiko perdarahan menjadi lebih besar.2,4
Target trombosit agar mencapai kondisi
hemostatik adalah 20-30x109/L.2 Apabila
jumlah trombosit di atas 50x109 /L, terapi tidak
lagi diperlukan.
Pada ITP sekunder yang disebabkan
infeksi HCV, eliminasi infeksi dengan obat
antivirus dapat meningkatkan trombosit
dan menurunkan kadar titer autoantibodi,7
namun interferon juga dapat menyebabkan
trombositopenia. Apabila terjadi perdarahan,
IVIg dapat menjadi lini pertama.1 Pada ITP
sekunder yang berhubungan dengan HIV,
terapi antiviral dapat langsung diberikan;
terapi ITP jika diperlukan adalah IVIg,
kortikosteroid, dan anti-D imunoglobulin.1
Apabila penyebab ITP adalah H.pylori, dapat
dilakukan eradikasi H.pylori.7
Pada ITP primer, terapi lini pertama terdiri dari
kortikosteroid, IVIg, dan IV anti-D, sedangkan
terapi lini kedua terdiri dari splenektomi dan
tindakan medis lain.2
Terapi Lini Pertama
Kortikosteroid oral menjadi pilihan utama
karena efek samping tidak parah, dan tidak
membutuhkan infus intravena;4 terdiri dari dua
regimen, yaitu prednison dan deksametason.
Terapi prednison standar dengan dosis 1-2
mg/kgBB/hari, diberikan hingga terlihat
respons, kemudian dosis dapat diturunkan
(tapered off).4,5 Deksametason diberikan per
oral 40 mg/hari selama 4 hari berturut-turut
dan dapat diulang hingga 3 siklus; dosis
tersebut adalah dosis tinggi. Pada penelitian
terdiagnosis lebih menguntungkan dengan
deksametason dosis tinggi dibandingkan
dengan prednison.10 Pada penelitian
tersebut, keuntungan yang didapat adalah
berkurangnya gejala perdarahan terutama
pada stadium awal ITP dan dosis tinggi
deksametason setara dengan pemberian
prednison konvensional sehingga dapat
659
 PO CKET G U I D E
ASH CLINICAL PRACTICE GUIDELINES
IMMUNE THROMBOCYTOPENIA (ITP)

Management
of Immune
Thrombocytopenia
(ITP)
A POCKET GUIDE FOR THE CLINICIAN
NOVEMBER 2019

Cindy Neunert, MD, Columbia University Medical Center

Sara K. Vesely, PhD, University of Oklahoma Health Sciences Center
Siraj Mithoowani, MD, McMaster University
Taylor Kim, MD, Baylor College of Medicine

The recommendations in this guide are based on the American Society of

Hematology 2019 Guideline for Immune Thrombocytopenia
Context
Immune Thrombocytopenia (ITP) is an acquired autoimmune disorder
characterized by a low platelet count resulting from platelet destruction and
impaired platelet production. The incidence of ITP is estimated to be 2 to
5 per 100,000 persons in the general population and can be an isolated
primary condition or it may be secondary to other conditions. The information
in this pocket guide is intended to support patients, clinicians, and other
health professionals in making evidence-based decisions about first-and
second-line management of adults and children with ITP.
Adult
INPATIENT VS. OUTPATIENT MANAGEMENT
TREATMENT
First-Line Therapies for Adults
In adults with newly diagnosed ITP, the ASH guideline panel recommends
against a prolonged course (>6 weeks) of prednisone in favor of a
short course (≤6 weeks) and suggests either prednisone (0.5 - 2.0
mg/kg/day) or dexamethasone (40 mg/day for 4 days) as the type of
corticosteroid for initial therapy1 . The ASH guideline panel suggests
corticosteroids alone rather than rituximab and corticosteroids for initial
therapy2 .
1
If a high value is placed on rapidity of platelet count response, an initial course of dexamethasone may be pre-
ferred over prednisone, given that dexamethasone increases the likelihood of a platelet count response at 7 days.
2
If high value is placed on possibility for remission over concerns for potential side effects of rituximab, then an
initial course of corticosteroids with rituximab may be preferred.

Table 1 – Inpatient vs. Outpatient Management

Good Practice Statement
Platelet Count Status Management For patients receiving corticosteroids, the treating physician should ensure
Platelet count of <20 x109/l Newly diagnosed Inpatient the patient is adequately monitored for potential side effects regardless of the
and asymptomatic or minor duration or type of corticosteroid selected. This includes close monitoring for
mucocutaneous bleeding Established diagnosis Outpatient1 hypertension, hyperglycemia, sleep and mood disturbances, gastric irritation
or ulcer formation, glaucoma, my­opathy and osteoporosis. Given the potential
Platelet count of ≥20 x109/l Newly diagnosed Outpatient1 impact of corticosteroids on mental health, the treating physician should
and asymptomatic or minor conduct an assessment of health-related quality of life (HRQoL) (depression,
mucocutaneous bleeding Established diagnosis Outpatient1 fatigue, mental status etc.) while patients are receiving corticosteroids.
1
Patients who are refractory to treatment, those with social concerns, uncertainty about the diagnosis, significant
comorbidities with risk of bleeding, and more significant mucosal bleeding may benefit from admission to the hospital. Second-Line Therapies for Adults
The need for admission is also variable across the range of platelet counts represented here (0-20 x109/l).
In adults with ITP lasting ≥3 months who are corticosteroid-dependent or
Good Practice Statement have no response to corticosteroids, the ASH guideline panel suggests
the following as potential second-line therapies (see Figure 1):
Patients not admitted to the hospital should receive education and expedited
follow-up with a hematologist within 24-72 hours. • Thrombopoietin receptor agonist (eltrombopag or romiplostim)1
• Rituximab
OBSERVATION VS. TREATMENT • Splenectomy2
Determining whether a patient with newly diagnosed ITP should be Follow the algorithm in Figure 1 to determine the most suitable second-
observed or requires pharmacological treatment depends on the degree of line therapies based on presentation and patient preferences.
thrombocytopenia, patient comorbidities, medications, and age – all of which 1
Individual patient preference may place a higher value on the use of a daily oral medication (eltrom­bopag) or one
impact the risk of bleeding. Management approaches vary based on disease that requires weekly subcutaneous injections (romiplostim).
duration, access to care, quality-of-life implications, and patient and provider 2
If possible, splenectomy should be delayed for at least one year after diagnosis because of the potential for
spontaneous remission in the first year.
preferences, among other factors.
Table 2 - Observation vs. Treatment (Newly Diagnosed ITP) Good Practice Statement
The treating physician should ensure that patients have appropriate
immunizations prior to splenectomy and that they receive counseling regarding
Platelet count ≥30 x 109/l and
asymptomatic or minor mucocutaneous Management with observation1 antibiotic prophylaxis following splenectomy. The treating physician should also
bleeding educate the patient on prompt recognition and management of fever and refer
to current recommendations on pre- and post-splenectomy care.
Platelet count <30 x 109/l and
asymptomatic or minor mucocutaneous Treatment with corticosteroids2 Each of the these second-line treatments may be effective therapy and
bleeding
there­fore the choice of treatment should be individualized based on
1
For patients with a platelet count at the lower end of this threshold, for those with additional comorbid­ities, antico-
duration of ITP, frequency of bleeding episodes requiring hospitalization
agulant or antiplatelet medications, or upcoming procedures, and for elderly patients (>60 years old), treatment with or rescue medication, comorbidities, adherence, medical and social
corticosteroids may be appropriate. support networks, patient values and preferences, cost, and availability.
2
This should include consideration of the severity of thrombocytopenia, additional comorbidities, use of anticoagulant
or antiplatelet medications, need for upcoming procedures, and age of the patient. For example, patients who place a high value on achieving a durable
response may prefer splenectomy or thrombopoi­etin receptor agonists
(TPO-RAs), patients who value avoidance of long-term medication may
prefer splenectomy or rituximab, and patients who wish to avoid surgery
may prefer a TPO-RA or rituximab. Patient education and shared decision-
making are encouraged.
 TINJAUAN PUSTAKA

7. Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6(2). pii: E16. doi: 10.3390/
jcm6020016.
8. Neunert CE. Current management of immune thrombocytopenia. American Society of Hematology. 2013;2013:276-82.
9. Stasi R. How to approach thrombocytopenia. Am Soc of Hematol. 2012;2012(1): 191-7
10. Wei Y, Ji XB, Wang YW, Wang Jx, Yang EQ, Wang ZC, et al. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: A prospective
multicenter randomized trial. Blood. 2016; 127(3):296-302; quiz 370.
11. Bohn JP, Steurer M. Current and evolving treatment strategies in adult immune thrombocytopenia. memo. 2018;11:241-6
12. Roorprai JK, Khamisa K. Is there a role for biweekly romiplostim in the management of chronic immune thrombocytopenia (ITP)? A report of three cases. Case Rep
Hematol. 2018;2018:6037494.
13. George JN. Sequence of treatments for adults with primary immune thrombocytopenia. Am J Hematol. 2012;20(87):12-15
14. Eghbali A, Azadmanesh P, Bagheri B, Taherahmadi H, Sadeghi Sedeh B. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of
immune thrombocytopenia: A randomized open-label study. Fundamental Clin Pharmacol. 2016;30(4):385-9.

CDK-280/ vol. 46 no. 11 th. 2019 661

Figure 1: Second-Line Therapies for Adults

Adult with ITP > 3 months

Dependent on or unresponsive
to corticosteroids

3-12 months Assess duration of ITP >12 months

Primary treatment options: Primary treatment options:

Rituximab, TPO-RA Rituximab, Splenectomy,
TPO-RA

Assess patient values Assess patient values

and preferences

Patient places a high Patient places a high Patient places a high Patient places a high Patient places
value on achieving value on avoiding value on achieving value on avoiding a high value on
durable response long-term medication durable response long-term medication avoiding surgery

Treatment options: Treatment options:

TPO-RA Rituximab Treatment options:
Splenectomy, Rituximab,
Rituximab, TPO-RA
TPO-RA Splenectomy

Figure 1. Selection of second-line therapy in adults with Patient Patient Patient Patient Patient Patient
ITP should be individualized based on duration of disease places a places a places a places a places a places a
and pa­tient values and preferences. Other factors that may high high high high high high
value on value on value on value on value on value on
influence treatment decisions include frequency of bleeding
avoiding avoiding avoiding durable achiving avoiding
sufficient to require hospitalization or rescue medication,
surgery long-term surgery response durable long-term
comorbidities, compliance, medical and social support
medication response medication
networks, cost, and availability of treatments. Patient
education and shared deci­sion-making is encouraged.
Patient characteristics
TPO-RA TPO-RA
Splenectomy Splenectomy
Rituximab Rituximab
Actions
Treatment options

TPO-RA – thrombopoietin receptor agonist

All recommendations in Figure 1 are conditional recommendations
Pediatric Second-Line Therapies for Children
In children with ITP lasting ≥3 months who have non-life-threatening
INPATIENT VS. OUTPATIENT MANAGEMENT mucosal bleeding and/or diminished health-related quality of life
Table 3 – Management of Newly Diagnosed ITP and do not respond to first-line treatment, the ASH guideline panel
suggests the following options for second-line therapies presented
Platelet Count Management in the order they should be pursued :
Platelet count of <20 x109/l and no or mild 1. Thrombopoietin receptor agonist (eltrombopag or romiplostim)1
Outpatient1
bleeding (skin manifestations) only 2. Rituximab
Platelet count of ≥20 x109/l and no or mild 3. Splenectomy2
Outpatient1
bleed­ing (skin manifestations) only 1
Individual patient preference may place a higher value on the use of a daily oral medication (eltrom­bopag)
or one that requires weekly subcutaneous injections (romiplostim). For pediatric patients, eltrombopag
1
For patients with uncertainty about the diagnosis, those with social concerns, those who live far from the dosing should avoid consumption of calcium containing foods such as dairy products by four hours. This
hospital, or those for whom follow-up cannot be guaranteed, admission to the hospital may be preferable. may limit the ability of some children to take this medication.
2
If possible, splenectomy should be delayed as long as possible after diagnosis because of the potential for
spontaneous remission in the first year.
Good Practice Statement
Patients not admitted to the hospital should receive education and Good Practice Statement
expedited follow-up with a hematologist within 24-72 hours.
The treating physician should ensure that patients have appropriate
immunizations prior to splenectomy and that they receive counseling
regarding antibiotic prophylaxis following splenectomy. The treating
OBSERVATION VS. TREATMENT physician should also educate the patient on prompt recognition and
In children with newly diagnosed ITP who have no or minor bleeding, management of fever and refer to current recommendations on pre- and
the ASH guideline panel recommends observation over both post-splenectomy care.
intravenous immunoglobulin and anti-D immunoglobulin , and
suggests observation over corticosteroids .
Each of the these second-line treatments may be effective therapy
TREATMENT and therefore the choice of treatment should be individualized based
First-Line Therapies for Children on duration of ITP, frequency of bleeding episodes requiring hospi-
talization or rescue medication, comorbidities, ad­herence, medical
In children with newly diagnosed ITP who have non-life-threatening
and social support networks, patient values and preferences, cost,
mucosal bleeding and/or diminished health-related quality of life, the
and availability. Patient education and shared decision-making are
ASH guideline panel suggests corticosteroids rather than intrave-
encouraged.
nous immunoglobulin or anti-D immunoglobulin1 . For patients where
corticosteroids are contra-indicated or otherwise not preferred, the
ASH guideline panel suggests either intravenous immunoglobulin or
anti-D immunoglobulin2 .
In children with newly diagnosed ITP who have non-life-threatening
mucosal bleeding and/or diminished health related quality of life,
the ASH guideline panel recommends against courses of
corticosteroids longer than 7 days in favor of courses 7 days or
shorter , and suggests prednisone (2 - 4 mg/kg/day; maximum, 120
mg daily, for 5-7 days) rather than dexamethasone (0.6 mg/kg/day;
maximum, 40 mg/kg/day, for 4 days) .
1
This recommendation assumes corticosteroid dosing as outlined in the following paragraph. This recom-
mendation is reserved only for children with non-major mucosal bleeding.
2
This recommendation is reserved only for children with non-major mucosal bleeding

Good Practice Statement

For patients receiving corticosteroids, the treating physician should ensure
the patient is adequately monitored for potential side effects regardless
of the duration or type of corticosteroid selected. This includes close
monitoring for hypertension, hyperglycemia, sleep and mood disturbances,
gastric irritation or ulcer formation, glaucoma, myopathy and osteoporosis.
Given the potential impact of corticosteroids on mental health, the treating
physician should conduct an assessment of health-related quality of life
(HRQoL) (depression, fatigue, mental status etc.) while patients are
receiving corticosteroids.
Strength of Recommendations and Quality of Evidence
The methodology for determining the strength of each recommendation and the quality of the
evidence supporting the recommendations was adapted from GRADE: an emerging consen-
sus on rating quality of evidence and strength of recommendations. Guyatt GH, et al; GRADE
Working Group. 2008;336(7650):924–926. More details on this specific adaptation of the
GRADE process can be found in American Society of Hematology 2019 Guideline for Immune
Thrombocytopenia.1
Strength of Recommendation
Strong recommendations - Most individuals should follow the recommended course of ac-
tion. Formal decision aids are not likely to be needed to help individual patients make decisions
consistent with their values and preferences.
Conditional recommendations - Recognize that different choices will be appropriate for indi-
vidual patients and that you must help each patient arrive at a management decision consistent
with his or her values and preferences. Decision aids may be useful in helping individuals to
make decisions consistent with their individual risks, values and preferences.

How to Use This Pocket Guide

ASH pocket guides are primarily intended to help clinicians make decisions about diag­nostic
and treatment alternatives. The information included in this guide is not intended to serve or
be construed as a standard of care. Clinicians must make decisions on the basis of the unique
clinical presentation of an individual patient, ideally though a shared process that considers
the patient’s values and preferences with respect to all options and their possible outcomes.
Decisions may be constrained by realities of a specific clinical setting, including but not limited
to institutional policies, time limitations, or unavailability of treatments. ASH pocket guides may
not include all appropriate methods of care for the clinical scenarios described. As science
advances and new evidence becomes available, these pocket guides may become obsolete.
Following these guide­lines cannot guarantee successful outcomes ASH does not warrant or
guarantee any products described in these guidelines.
The complete 2019 ASH Clinical Practice Guideline for Immune Thrombocytopenia1 include
additional remarks and contextual information that may affect clinical decision­making. To learn
more about these guidelines, visit hematology.org/ITPguidelines.
Conflict of interest information for Drs. Neunert, Vesely, Mithoowani, and Kim may be found at
hematology.org/pocketguidesCOI.
1
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guideline for immune
throm­bocytopenia. Blood Adv. 2019. In press.

This and other ASH pocket guides are also available in the ASH Pocket
Guides App, available for Android and iOS devices. More infor­mation
about this and other ASH pocket guides may be found
at hematology.org/pocketguides.

© 2019 American Society of Hematology

All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system, or transmitted in any form or by any means, electronic or mechanical, including
photocopy, without prior written consent of the American Society of Hematology.

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Washington, DC 20036
www.hematology.org

For expert consultation on immune thrombocytopenia and other hematologic questions,

submit a request to the ASH Consult a Colleague program at
www.hematology.org/consult (ASH members only).