HOW I TREAT IDIOPATHIC

THROMBOCYTOPENIC
PURPURA

Dairion Gatot , Soegiarto Gani, Savita Handayani

Hematology -Onkology Medical Division

Internal Departement of Medical Faculty
of North Sumatera University /
Haji Adam Malik General Hospital
Medan 2010
 INTRODUCTION

TO SET FORTH APROACH TO MANAGING ADULTS

PRIMARY (AUTOIMMUNE) ITP FROM ASH & THE
BRITISH COMMITTEE FOR STANDARDS IN
HAEMATOLOGY GENERAL HAEMATOLOG Y TASK
FORCE :

1.WHO DEVELOPS ITP ?

2.HOW DIAGNOSIS ITP ?
3.WHO WE TREAT ITP
4.ITP AND PREGNANCY

-
 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
Cines D.B. Blanchette V.S. Immune Thrombocytopenic. N Engl J Med. March
George JN, el Harake MA, Aster RH. Thrombocytopenia due to enhanced pla
By immunologic mechanism, in Beutler E, Litchmann MA, Coller BS, Kipps T
 HOW WE DIAGNOSE ITP

- DIAGNOSIS OF EXCLUSION
- ESSENSIAL ELEMEN : ISOLATED
THROMBOCYTOPENIA,
PERIFERAL SMEAR (UNREMARKABLE),
- PHYSICAL EXAMINATION (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
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 (30-

40%)
DI NOT RESPON OR RELAPSE
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
PLT growth and development factor inpatients with idiopathic thromb
Karyocyte
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