BAGAIMANA MEMPERLAKUKAN

IDIOPATHIC
THROMBOCYTOPENIC PURPURA

MELLA FERDIKA ARTHA

WHO DEVELOPS ITP ?

TYPICAL ITP : ADULT WOMAN
AGE : BETWEEN 18 AND 40 YEARS
TWO PUBLICATION HAVE QUESTIONED THIS
PERCEPTION :
DENMARK (SURVEY)
-THE FEMALE-MALE RATIO =1. 7 : 1
-MEDIAN AT DIAGNOSIS 56 YEARS
ENGLAND (PROSPECTIVE COHORT)
(PLATELET (PLT) < 50.000X109/L
-THE FEMALE-MALE RATIO =1.2 : 1
-HIGHEST >60 YEARS

Frederiksen H, Schmidt. The Incidence of Idiophatic Thrombocytopenic

Purpura in Adult

BAGAIMANA KITA MENDIAGNOSA ITP

- Diagnosis eksklusi
- Essensial elemen: Isolated thrombocytopenia, periferal
smear (unremarkable)
- Pemeriksaan fisik: (BLEEDING CONSISTENT WITH PLT
COUNT)

Stasi R, Provan D. Management of Immune Thrombocytopenic Purpura in

Adult

- BMP (RUTINE)
> TYPICAL PATIENT >60 YEARS
> DON`T SHOW A ROBUST RESPONSE
(PLT>50.000)
> PRIOR SPLENECTOMY
> EVALUATION OF RESPONSE IVIG, anti-D
> POOR RESPONSE TREATMENT

WHO WE TREAT
PLT <20.000/MM3
WITH BLEEDING MANIFESTATION OR
NOT
10-YEAR STUDY OF 310 PT (PLT<30.000)
1 HEMORRHAGIC DEATH
META-ANALYSIS OF 17 STUDIES, THE AGE ADJUSTED
RISK OF FATAL HEMORHAGE WITH PLT <30.000

<40 Y
0,4%,
40-60 Y
1,2%,
>60 Y
13%
5Y MORTALITY 2,2 TO 47,8%

TREATMENT AT PRESENTATION
PRINCIPLES OF MANAGEMENT
PLT<20.000, WITH PETECHIAE OR PURPURA,
THE ONSET MORE OFTEN INSIDIOUS THAN
PREVIOUSLY
PLT<10.000, SEVERE CUTANEOUS
BLEEDING,PROLONGE EPISTAXIS, GINGGIVA
BLEEDING, OVERT HEMATURIA, OR MENORRHAGIA
PLT COUNTS :
10.000-20.000,
SPONTANEOUS BLEEDING
30.000 TO 50.000,
MAY NOT EASY BRUISING
>50.000,
DISCOVERED INCIDENTALLY

PLT COUNT : 30.000

INITIAL GOAL OF TREATMENT
PLT 20.000 TO 50.000
IMMIDIATE TH/ IS NOT REQUIRED.
IN ABSENCE OF BLEEDING OR PREDISPOSING
COMORBID UNCONTROLED HT, ACTIVE PEPTIC
ULCER DISEASE , ANTICOAGULATION, RECENT
SURGERY OR HEAD TRAUMA.
PLT 40.000 TO 50.000,
RECOMMENDED, REQUIRING ASPRIN, NSAID,
WARFARIN, OR ATHER ANTITHROMBOTICS.

Cines D.B. Blanchette V.S. Immune Thrombocytopenic. N Engl J Med. March

Splenectomy.
Wang T, Xu M, Ji l, Han Zc, Yang R. Splenectomy for adult chronic
idiopathic
Thrombocytopenic Purpura: eaperiance from a single center in China.
Eur J Haematol 2005;75:424-429
Corticosteroid,
Kitchens C.S, Pendergast J.F. Human Thrombocytopenia is associated
with
structural abnormalities of endothelium that are ameliorated by
glucocorticosteroid administration. Blood 1986;67:203-206

IVIG, anti-D immune globulin,

Song S, Crow A.R, Siragam V, Freedman J, Lazarus A.,H. Monoclonal
antobodies thar mimic The action of anti-D in the amelioration of murine
ITP act
by a mechanism distinct from that Of IVIg. Blood. 2005;105:1546-48
Berchtold P, Dale GL, Tani P, McMillan R.. Inhibition of Autoantibody to
Platelet
Glycoprotein IIb/IIIa by Anti-Idiotipic Antibodies in intravenous
Gammaglobulin.
Blood 1989: 2414-2417
Kuwana M, Kaburaki J, Kitasato H, et all. Immunodominant epitopes on
glycoprotein IIb-IIIa Recognized by autoreactive T cell in patients with
immune
thrombocytopenia purpura. Blood 2001;98:130-139
Crow A.R, Song S, Freedman J, et all. IVIg-mediated amelioration of
murine ITP
via FcyRIIB is Independent of SHIP1, SHP-1, and Btk activity.
Blood.2003;

Azathioprin, Cycophaspamide, Cyclosporin, Carticosteroid, danazole

Kuwana M, Kaburaki J, Kitasato H, et all. Immunodominant epitopes
on
Glycoprotein IIb-IIIa Recognized by autoreactive T cell in patients
with
mmune thrombocytopenia purpura. Blood2001;98:130-139

Cines D.B. Blanchette V.S. Immune Thrombocytopenic. N Engl J Med. March

HOSPITALIZATION AND EMERGENCY THERAPY

HOSPITALIZED :
1.PROFOUND MUCUCUTANEOUS OR INTERNAL
BLEEDING
2.PLT 20.000
BLEEDING & HISTORY OF SIGNIFICANT
COMPLIANCE
RESPON TH/ HAS NOT BEEN ESTABLISHED

REDUCE RISK OF BLEEDING (GENERAL):

-CESSATION OF DRUG THAT IMPAIR PLT FUNCTION
-CONTROL BP
-MINIMIZE TRAUMA
-REDUCE MUCOSAL BLEEDING
E-AMINOCAPROIC ACID ( 100mg/KB LOADING
DOSE
UP TO MAX OF 5 gr IV OVER 30-60 MNT FOLLOW
UP BY
5 gr EVERY 6 H IV OR ORALLY (MAX DOSE=24
gr/DAY)
TRANEXAMIC ACID
DESMOPRESSIN ACETAT (DDAVP; 0,3 ug/KB)

INITIAL THERAPY FOR NONEMERGENT INDICATIONS

THERE IS NO CONSENSUS OPTIMAL DURATION

OF CORTICOSTEROID
CONTINUE FULL DOSE FOR 3 to 4 WEEKS
TAPERRING PREDNISON SLOWLY, ONCE DOSES OF
10 MG/DAY ARE REACHED
RESPON RATE 50-90%
STABEL REMISI 10-30%

PERSISTEN ITP
THROMBOCYTOPENIA RECURS WHEN
CORTICOSTEROID
ARE TAPERED
TARGET PLT > 20.000 to 30.000

MAYOR DECISION : SPLENECTOMY

SPLENECTOMY
BEST OPTION
TIMING OF THE PROCEDURE DEPENS ON :
-DISEASE SEVERITY,
-RESPONSIVNES AND SIDE EFFECT OF THERAPY
-RISK OF THE TRAUMA AND OF THE
PROCEDURAL
AND PATIENT AND DOCTOR PREFERENCE.

RECOMMENDED :
ANY THERAPY (PREDNISON >10mg/D) FAILURED
(PLT <30.000) (3 to 6 MO)
PLT <20.000 or DIFFICULT TO CONTROPL
BLEEDING
DISEASE DO NOT ABATE BY 1 YEAR AFTER
DIAGNOSIS
DO NOT SHOW DURABLE RESPONSE
INTOLERAN OF THERAPY

HOW ABAUT THE APROACH ?

A 75 Y-OLD ASYMPTOMATIC,
PLT<18.000,
A LIFE EXPENTANCY OF 8 to 12 Y,
SIGNIFICANS RISK FROM SURGERY.
ACTIVE YOUNG ADULT WITH EASY BRUISING OR
SIGNIFICANS MENORRHAGIA ,
PLT 20.000 to 30.000,
LIFE EXPENTANCY 50 to 60 Y, AND
NO SIGNS OF ABATING

BEFORE SPLENECTOMY :
IV IG, IV ant-D or PULSE DOSE OF
CORTICOSTEROID
AFTER SPLENECTOMY :
85% HEMOSTATIC RESPONSE
2/3 DURABLE RESPONSE.
INCIDENSSE RELAPSES 15 to25% WITH IN 10 Y
MORTALITY RATE FOR OPEN AND LAPAROSCOPIC
SPLENECTOMY ARE 1,0 % and 0,2%

LONG TERM RISK SPLENECTOMY :

BACTERIAL SEPSIS <1%
IMMUNIZE WITH VACCINES AT LEAST 2 WEEK
PRIOR
-POLYVALENT PNEUMOCOCCAL,
-H INFLUENZA Type b,
-QUADRIVALENT MENINGOCOCAL POLYSACCHARIDA
REVACCINATION PNEUMOCCOCAL EVERY 5 t0 10 Y

THE EXPERIENCE :
MOST PTS RESPOND TO VACCINATION GIVEN
MORE
THAN 6 WEEK AFTER SURGERY
DO NOT RECOMMENDED LIFE LONG USE OF :
-PHENNOXYMETHYL-PENICILLIN (250-500 mg
PO/12H)
-ERYTHROMYCIN (500 mg PO TWICE DAILY)

TREATMENT OF CHRONIC ITP

PRINCIPLES OF TREATMENT
PLT <50.000 AFTER SPLENECTOMY (3040%)
DI NOT RESPON OR RELAPSE

FIRST-LINE THERAPY

SYMPTOMATIC RELAPSES OR SEVERE RECURRENT

THROMBOCYTOPENIA IN THE SAME WAY AS AT
INITIAL PRESENTATION CORTICOSTEROID OR IV IG
OR EMERGENT MEASURES
(HOSPITALISASI AND EMERGENCY THERAPY)E .

Anti-CD20 (RITIXIMAB 375 mg/m2 IV

EVERY WEEK FOR 4 WEEK
RESPONSES : 4 8 week (4 MO)
COMPLET OR PARTIAL REMISSION 25-50%
MANY COMPLET RESPONSES ARE DURABLE (>1Y)
NO RESPON RITUXIMAB
TWO AGENT TO AVOID INDUCING MULTIPLE DRUG
RESISTANCE GENES
(DANAZOLE, AZATHIOPRINE or MYCOPHENOLATE
MOFETIL TREAT 4 to 6 MO (FULL EFECT)
RESPONS CORTICOSTEROID TAPPERED AND IVIG
STOP

AZATHIOPRIN 2mg/kg PO DAY

DANAZOLE 10 -15mg/ kg/DAY (600-800mg PER DAY)
RESPON OCCURS 3-4 MO CONTINUE AT FULL
DOSE
FOR >12 MO AND DISCONTINUE GRADUALLY
REMISION : 20-40%
DAPSON : 75-100 mg PO SIMILAR DANAZOLE
(avoid if G6PD def)
MYCOPHENOLATE MOFETIL 500 mg PO TWICE A DAY
INCREASE to 1000 to 1500 PO TWICE A DAY AFTER
2 WEEKS.
.

TREATMENT OF CHRONIC ITP

SECOND-LINE THERAPY

CYCLOPHOSPHAMIDE :
INTRAVENA 500-1000 mg /m2
(2 OR 3 COURSE) AT 3-4 WEEK INTERVAL, Or
PO 1-2 mg/kg DAILY
(RESPONSE 1-3 MO)
CsA 1,25 2,5 mg/kg/ DOSE PO EVERY 12 HOURS

TREATMENT OF CHRONIC REFRACTORY ITP

DEFINE CHRONIC REFRACTORY ITP AS FAILURE
OF ANY MODALITY TO KEEP PLT >20.000 (5%)
CsA 1,25 2,5 MG/KG/ DOSE PO EVERY 12 HOURS
CYCLOPHOSPHAMIDE 1.0-1,5 G/M2 IV (4 WEEK
INTERV)

EXPERIMENTAL THERAPY
THROMBOPOETIC FACTOR
STUDY PEGYLATED RECOMBINAT HUMAN
MEGAKARYO
CYTE 2 OF 4 PTS DEVELOPED TEMPORARY
THROMBOCYTOSIS

STUDY 2 PLACEBO-CONTROL TRIAL AMG-531

(MOLECUL THROMBOPOIETIN RECEPTOR)
(DOSE >3,0 ug/Kg) 8 OF 12 PTS AND 7 OF 8
PTS
SHOWED TEMPORARY BUT SUBSTANTIAL
INCREASES
Nomura S, Dan K, Hotta T, Fujimura K, Ikeda Y. Effects of pegylated recomb
Karyocyte
PLT growth and development factor inpatients with idiopathic thromb

Blood. 2002;100:728-730
Emmons V.B, Reid D.M, Cohen R.L, et all. Human Thrombopoietin levels are
Thrombocytopenia is due to megakaryocyte deficiency and low when due to
Destruction. Blood 1996;87:4068-71

AUTOLOGOUS STEM CELL TRANSPLANT :

REPORTED 14 PTS REFRACTORY ITP MORE THAN 6
MO AFTER TRANSPLANT
SIX PTS STABLE PLT (>100.000),
AND 2 PTS PARTIAL , ( 9 42 MO)
THERE WERE NO PROCEDURAL DEATHS
SEPSIS UNCOMMON
TWO OF 6 PTS COMPLET RESPON DIED WITHIN
YEAR

Huhn RD, Forgaty PF, Nakamura R. et all. High-dose cyclophosphamide

with autologus
Lymphocyte depleted periperal blood (PBSC) support for treatmeny of

ITP AND PREGNANCY

CONSULT TO THE PHYSICIAN :
-SAFE PREGNANCY
-DIAGNOSIS
-DIFFRENTIAL DX:
HELL SYNDROME (pregnancy induced
hypertension
and related condition such as
hemolysis,elevated
liver enzyms, and low PLT count)
-OBSTETRIC CAUSE of DIC,
-MICROANGIOPATHIC HEMOLYTIC PROCESSES,
-GESTATIONAL THROMBOCYTOPENIA.

-INCIDENCE : 1 per 1.000 to 10.000 PREGNANCY

MILD THROMBOCYTOPENIA : PLT < 70.000 (95%)
-NO IMPACT ON MATERNAL & FETAL DEATH
-NORMAL 2 MO OF DELIVERY
ITP (SUSPECT) PLT <50.000 ( trimester 2)
ABSENCE OF SYMPTOM OR TREATMENTMONITOR
PLT :
-at least monthly through the first trimester 2
-biweekly in the third
-weekly as term or more if indicated

PLT (ideal)

> 20.000 THROUGHT PREGNANCY

> 50.000 NEAR TERM
PLT(higher) Epidural anasthesi
THERAPY :
INITIAL CORTICOSTEROID
PREDNISON (low dose) : 20 mg every day
IVIG
IV anti-D (safe and efective) (limited experience)
AZHATHIOPRIN possible exception for Renal
Transplant

DELIVERY IS BASED ALMOST ENTIRY

PPH IS UNCOMMON EVEN WITH SEVERE
THROMBOCYTOPENIA
NEONATUS BORN :
> ITP NEONATES BORN (4%) PLT<20.000
>SEVERITY d1 to d3
>No ANTENATAL MATERNAL MEASURE PREDICT
NEONATAL PLT
>MEASURE PLT cord; FIRST WEEK POST PARTUM
DECREASED ONSET OF THROMBOCYTOPENIA
>PLT<50.000 SONOGRAPHY : CT SCANNING, MRI

CONCLUSION

THE INCIDENCE ITP INCREASED WITH INCREASE

AGE
DIAGNOSIS ITP PEREXCLUSION
TREATMENT ITP; EMERGENCY AND NONEMERGENCY
TREATMENT WHEN PLT <20.000/MM3 AND TARGET
PLT >30.000/MM3
MINIMAL EMERGENT THERAPY INCLUDE IV METHYLPREDNISOLONE AND IVIG.
THERAPHY MINIMUM 3 MO AND MAXIMUM 12 MO
SPLENECTOMY:SINGLE BEST OPTION FOR
PERSISTEN ITP

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