Program Workbook

Management of Immune
Thrombocytopenic Purpura (ITP)
in Children
With Michael D. Tarantino, MD
University of Illinois College of Medicine
Peoria, IL

Provided as an educational service by Cangene bioPharma

bioPharma

Management of ITP in Children

This educational program, provided as a
service by Cangene bioPharma, is designed
for healthcare professionals who treat children.
Featuring Dr. Michael Tarantino, the Medical
Director of the Bleeding and Clotting Disorders
Institute and Professor of Pediatrics and Medicine
at the University of Illinois College of Medicine
Peoria, this presentation provides guidance on
the diagnosis, management and treatment
of pediatric ITP.

Current Perspectives in the Management of Immune Thrombocytopenic Purpura (ITP)

Notes:

Management of
Pediatric ITP

Provided as an educational service by Cangene bioPharma

Michael D. Tarantino, MD
Medical Director
The Bleeding and Clotting Disorders Institute
Professor Of Pediatrics and Medicine
University of Illinois College of Medicine-Peoria
Peoria, IL

bioPharma

The objectives of this program are to

Understand the pathophysiology of ITP
Recognize the signs and symptoms of ITP
Become familiar with recommended first-line therapies

Notes:

Understand the risks and benefits of recommended first-line therapies

Michael D.Tarantino, MD

Medical Director
The Bleeding and Clotting Disorders Institute
Professor Of Pediatrics and Medicine
University of Illinois College of Medicine-Peoria
Peoria, IL

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

Management of Pediatric Immune

Thrombocytopenic Purpura (ITP)

Notes:

Overview
Pathophysiology
Diagnosis
Classification
First-line therapy
Experience with anti-D

Overview of Pediatric ITP

Notes:

Triggers of ITP are not entirely known

Major or minor bleeding is difficult to predict,
but severe bleeding is uncommon

Drugs used to treat ITP work in a variety of ways

and have characteristic side effect profiles

ITP commonly resolves spontaneously in children,

less commonly in adults

Cines DB et al. N Engl J Med. 2002;246:995-1008.

Provan D et al. Blood. 2010;115:168-186.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Notes:

Overview

Notes:

Pathophysiology

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

Notes:

Pathophysiology
Autoimmune-Driven Processes

Notes:

ITP Symptoms

Bruising and petechiae

Epistaxis
Mucosal and gum bleeding
GU hemorrhage
GI hemorrhage
Intracranial hemorrhage

Common
Common
Less common
Less common
Rare
Rare

For a more detailed presentation on this topic, visit the Platelet Disorder Support Association (PDSA) website
at http://store.shoppdsa.org/394.html to purchase Pathophysiology of ITP and Current Therapies DVD
Cines DB et al. N Engl J Med. 2002;346:995-1008.
Olsson B et al. Nat Med. 2003;9:1123-4.

Buchanan GR, Adix LM. J Pediatr. 2002;141(5):683-688.

Notes:

FREQUENCY

Spectrum of Disease

Notes:

Diagnosis
ASYMPTOMATIC
MUCOCUTANEOUS
BLEEDING
INTRACRANIAL
HEMORRHAGE
SEVERITY

Buchanan GR et al. J Pediatr. 2002;141(5):683-688.

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

Diagnosis of ITP

Notes:

Isolated thrombocytopenia with associated purpura

Diagnosis of exclusion

Which Children are Likely to Have

Serious Bleeding?

Notes:

Wet purpura
Aspirin users
Head trauma
Low platelet count (<10,000/mm3)

Look for enlarged spleen, liver, and lymph nodes

permissive but not sufficient evidence

About 3/4 of children with serious bleeding had
a platelet count <10,000/mm3

Medeiros D et al. Pediatric Clinics of North America. 1996;43:757-772.

Butros LJ et al. J Pediatr Hematol Oncol. 2003;25(8):660664.
Psaila B et al. Blood. 2009;114:4777-4783.

British Committee for Standards in Haematology General Haematology Task Force. Br J Haematol. 2003;120(4):574-596.

Classification of ITP

Notes:

Notes:

Traditional

Acute (6 months duration)

Chronic (6 months duration)

2010 International Consensus Guidelines

Newly diagnosed
Persistent (3-12 months duration)
Chronic (12 months duration)

First-Line Therapy

Rodeghiero F. Eur J Haematol Suppl. 2008;69:19-26.

Imbach P et al. Pediatr Blood Cancer. 2006;46:351-356.
Kuhne T et al. J Pediatr. 2003;143:605-608.
Provan D et al. Blood. 2010;115:168-186.

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

First-Line Treatment of Pediatric ITP:

2010 International Consensus Guidelines

Notes:

Anti-D (if Rh+) nonsplenectomized,

First-Line Therapy:
IVIG

Notes:

Rapid platelet response

Plasmaderived
3+ hour infusion time
Expensive
Side effects

50-60 g/kg x 1

IVIG

0.8-1 g/kg x 1-2 doses

Infusion reactions

Corticosteroids

Headache, fever, chills, nausea

Prednisone, 1-2 mg/kg/day, taper off in 3 weeks

Rare complications
Aseptic meningitis
Kidney impairment or failure
Hemolytic anemia

George JN et al. Blood. 1996;88(1):3-40.

Stasi R et al. Mayo Clin Proc. 2004;79(4):504-522.

Provan D et al. Blood. 2010;115:168-186.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

First-Line Therapy:
Corticosteroids
Inexpensive
Side effects may be treatment limiting and include
Avascular necrosis
Diabetes
Gastritis, ulcers
Growth retardation
Hypertension
Insomnia
Personality changes
Opportunistic infection

Most side effects are dose and duration dependent

Platelet counts decrease immediately after therapy is discontinued
Rodeghiero F. Eur J Haematol Suppl. 2008;69:19-26.
Sandler SG et al. Expert Opin Pharmacother. 2004;5:2515-2527.
Stasi R et al. Mayo Clin Proc. 2004;79:504-522.

Notes:

First-Line Therapy:
IV Anti-D Immune Globulin

Notes:

Plasma derived
Infused in 3-5 minutes
Platelet response may be dose related
Side effects
Infusion reactions
Headache, fever, chills, nausea
Hemolysis
Mean decrease in hemoglobin usually <2 g/dL
Hemoglobin decrease 2 g/dL has rarely been associated with renal failure and DIC
Monitor patients for 8 hours post-infusion for signs and symptoms of IVH. Use another
agent if patient has autoimmune hemolytic anemia with pre-existing hemolysis, renal
impairment or +DAT.
Cines DB et al. N Engl J Med. 2002;346(13):995-1008.
Scaradavou A et al. Blood. 1997;89(8):2689-2700.
Gaines AR. Blood. 2005;106(5):1532-1537.
Gaines AR. Blood. 2000;95(8):2523-2529.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

10

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

11

Notes:

How I Manage Pediatric ITP*

Notes:

Establish diagnosis of ITP

Treat if:
Wet purpura
Platelets <10,000/L
Lack of access to emergency care
Observe if:
Dry purpura only
Platelets >20,000/L
Reliable caregivers
Ready access to emergency care

Anti-D Experience

*Intended solely as a guideline.

Stasi R et al. Mayo Clin Proc. 2004;79(4):504-522.
Song S et al. Blood. 2005;105(4):1546-1548.
Cooper N et al. Br J Haematol. 2004;124(4):511-518.

IV Anti-D Immune Globulin

Mechanism of Action
Mechanism of action*

(MOA)
Binds to Rh+ red
blood cells
Antibody-coated red
blood cells compete
with coated platelets
for clearance by
macrophages
*MOA not completely understood.

Notes:

Rationale for Continued Use of WinRho SDF

[Rho(D) Immune Globulin Intravenous (Human)]*

Notes:

Only anti-D licensed for pediatric use

Overall response rates in acute ITP
Increase in platelet levels after 1 and 3 days

Overall response rates in chronic ITP

Average duration of response is 30 days

Dose can be adjusted based on response and hemoglobin level

IV anti-D may be an effective alternative to IVIG as it can be
infused in a shorter time, is produced from a smaller donor pool
[and] has a potentially longer response
Provan et al. Blood. 2010.

12

Stasi R et al. Mayo Clin Proc. 2004;79(4):504-522.

Song S et al. Blood. 2005;105(4):1546-1548.
Cooper N et al. Br J Haematol. 2004;124(4):511-518.

*Intended solely as a guideline.

Provan D et al. Blood. 2010;115:168-186
WinRho SDF Prescribing Information, December 2010.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

13

WinRho SDF [Rho(D) Immune Globulin Intravenous

(Human)] vs IVIG in Acute Pediatric ITP

Notes:

Response Rates in Children with Chronic ITP

Response rates in children (N=24)

In a pivotal trial (N=146), there was no significant difference in response rates

between WinRho (84.2%), low-dose IVIG (90.0%) or high-dose IVIG (93.1%)*

WinRho SDF Liquid is Bioequivalent to WinRho SDF Lyophilized

79%

In two comparative pharmacokinetic studies (N=101), the formulations were bioequivalent

following IV administration based on the area under the curve to 84 days and had comparable
pharmacokinetics following IM administration. Both formulations also had similar elimination
half-lives. WinRho SDF must be administered via the intravenous route for the treatment of ITP.

*Study performed using WinRho

administered in a dose range of
25 to 55 g/kg.
Response defined as a doubling
of pretreatment platelet counts to
50,000/mm3.
Duration of response defined as days
from administration of last infusion to
the occurence of first platelet count
<15,000/mm3 over baseline levels or
to end of observation period.

In clinical studies, the mean duration of response* in children with chronic ITP
was 36.5 days.

*Study performed using WinRho. Patients received WinRho 25 g/kg on days 1 and 2; IVIG 0.8 g/kg on day 1 and 1.0 g/kg
on days 1 and 2. Response defined as an increase in absolute platelet count to >50,000/mm3.
WinRho SDF Prescribing Information, December 2010.
Data on file, Cangene Corporation.

WinRho SDF Prescribing Information, December 2010.

Data on file, Cangene Corporation.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Response Rates of WinRho SDF [Rho(D) Immune Globulin

Intravenous (Human)]

vs IVIG in Children with Acute ITP

Response rates in children receiving 2 consecutive doses of IVIG

or a single dose of WinRho
P= Nonsignificant

76%

69%

93%

Day 1
IVIG
1.0 g/kg/d for 2
days (n=29)

WinRho
50 g/kg single
dose (n=25)

92%

Day 3
IVIG
1.0 g/kg/d for 2
days (n=29)

WinRho
50 g/kg single
dose (n=25)

Randomized, prospective
trial of 54 Rh-positive
(presumed DD genotype)
Korean children newly
diagnosed with ITP.
Patients were randomly
assigned to receive either
2 consecutive doses of IVIG
at 1.0g/kg/d or a single dose
of WinRho at 50 g/kg.
Response defined as platelet
count over 20,000/mm3.

Notes:

Notes:

WinRho has a Safety and Tolerability Profile

Established in Clinical Trials

Notes:

In clinical trials, 7% of WinRho* infusions had at least 1adverse reaction

The most common adverse reactions were: headache (2%), chills (<2%) and fever (1%),
which are expected adverse drug reactions following intravenous administration of human
immune globulins

WinRho SDF Liquid is Bioequivalent to WinRho SDF Lyophilized

In two comparative pharmacokinetic studies (N=101), the formulations were bioequivalent
following IV administration based on the area under the curve to 84 days and had comparable
pharmacokinetics following IM administration. Both formulations also had similar elimination
half-lives. WinRho SDF must be administered via the intravenous route for the treatment of ITP.

*Studies performed using WinRho/WinRho SD

WinRho SDF Prescribing Information, December 2010.
Son DW et al. J Pediatr Hematol Oncol. 2008;30:598-601.

Please see Important Risk Information including Boxed Warning at the end of this presentation.

14

Please see Important Risk Information including Boxed Warning at the end of this presentation.

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

15

Notes:

Conclusion

Notes:

Pediatric ITP may range in severity from asymptomatic to

mucocutaneous bleeding to intracranial hemorrhage
Often resolves spontaneously

Diagnosis of exclusion
Bruising and petechiae are common symptoms

2010 International Consensus Guidelines recommend

anti-D immune globulin, IVIG and corticosteriods as first-line therapy
WinRho SDF [Rho(D) Immune Globulin Intravenous (Human)] remains
a beneficial first-line therapy in the treatment of pediatric ITP

Cines DB et al. N Engl J Med. 2002;246:995-1008.

Buchanan GR et al. J Pediatr. 2002;141(5):683-688.
Provan D et al. Blood. 2010;115:168-186.

Notes:

For a more detailed presentation on the pathophysiology and

treatment of ITP, visit the Platelet Disorder Support Association
(PDSA) website at http://store.shoppdsa.org/394.html to purchase
the Pathophysiology of ITP and Current Therapies DVD.
Thank you.

WinRho SDF is a registered trademark of Cangene Corporation.

Manufactured by Cangene Corporation. Distributed by Cangene bioPharma, Inc.
2011 Cangene Corporation. All rights reserved. CBI-WR-PLLVID-2011-02

16

Please see Important Risk Information and

Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

17

Indications and Important Risk Information

Indications and Usage
WinRho SDF [Rho(D) Immune Globulin Intravenous (Human)] must be administered via the intravenous route
when used in clinical situations requiring an increase in platelet count to prevent excessive hemorrhage in the
treatment of non-splenectomized, Rho(D)-positive:
children with chronic or acute ITP,
adults with chronic ITP, or
children and adults with ITP secondary to HIV infection
The safety and efficacy of WinRho SDF has not been evaluated in clinical trials for patients with non-ITP causes
of thrombocytopenia or in previously splenectomized patients or in patients who are Rho(D)-negative.
WinRho SDF Liquid is Bioequivalent to WinRho SDF Lyophilized1
In two comparative pharmacokinetic studies (N=101), the formulations were bioequivalent following IV administration
based on the area under the curve to 84 days and had comparable pharmacokinetics following IM administration.
Both formulations also had similar elimination half-lives. WinRho SDF must be administered via the intravenous
route for the treatment of ITP.

Important Risk Information

WARNING: INTRAVASCULAR HEMOLYSIS (IVH)
Intravascular hemolysis (IVH) leading to death has been reported in patients treated for immune
thrombocytopenic purpura (ITP) with WinRho SDF.
IVH can lead to clinically compromising anemia and multi-system organ failure including acute
respiratory distress syndrome (ARDS).

WinRho SDF is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses,
and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
The safety and efficacy of WinRho have not been evaluated in clinical trials for patients with non-ITP causes of
thrombocytopenia or in previously splenectomized patients or in patients who are Rho(D)-negative.
Acute renal dysfunction/failure, osmotic nephropathy, and death may occur upon use of Immune Globulin
Intravenous (IGIV) products, including WinRho SDF. Ensure that patients are not volume depleted before
administering WinRho SDF. For patients at risk of renal dysfunction or failure, including those with any degree
of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion,
sepsis, paraproteinemia, or receiving known nephrotoxic drugs, administer WinRho SDF at the minimum infusion
rate practicable.
In Rho(D)-positive patients with ITP, side effects related to the destruction of Rho(D)-positive red blood cells,
most notably decrease hemoglobin, can be expected. In most cases, the red blood cell destruction is believed
to occur in the spleen.
Thrombotic events may occur following treatment with WinRho SDF and other IGIV products.
Noncardiogenic pulmonary edema [Transfusion-related Acute Lung Injury (TRALI)] may occur in patients following
IGIV treatment.
General adverse reactions associated with the use of WinRho SDF include body weakness, abdominal or back
pain, low blood pressure, paleness, diarrhea, abnormal blood work, joint pain, muscle pain, dizziness, abnormal
movement, sleepiness, itchiness, rash, and sweating. In the treatment of ITP, the most common adverse events
(2% of infusions) were headache, chills, and fever.

Serious complications including severe anemia, acute renal insufficiency, renal failure and
disseminated intravascular coagulation (DIC) have also been reported.
Closely monitor patients treated with WinRho SDF for ITP in a healthcare setting for at least 8 hours
after administration. A dipstick urinalysis to monitor for hematuria and hemoglobinuria is to be
performed at baseline and then after administration at 2 hours, 4 hours and prior to the end of the
monitoring period. Alert patients and monitor the signs and symptoms of IVH including back pain,
shaking chills, fever, and discolored urine or hemoglobinuria. Absence of these signs and/or symptoms
of IVH within 8 hours do not indicate IVH cannot occur subsequently. If signs and/or symptoms
of IVH are present or suspected after WinRho SDF administration, posttreatment laboratory tests
should be performed including plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct
and indirect).
For use in the treatment of ITP, do not use WinRho in:
Patients who have had known anaphylactic or severe systemic reaction to the administration of human immune
globulin products.
IgA deficient patients with antibodies to IgA and a history of hypersensitivity.
Patients with autoimmune hemolytic anemia, with pre-existing hemolysis or at high risk for hemolysis.
Infants for the suppression of Rho(D) isoimmunization.
The liquid formulation of WinRho SDF contains maltose. Maltose in IGIV products has been shown to
give falsely high blood glucose levels in certain types of blood glucose testing systems. Due to the
potential for falsely elevated glucose readings, only testing systems that are glucose-specific should
be used to test or monitor blood glucose levels in patients receiving WinRho SDF Liquid.

18

Please see accompanying full Prescribing

Information for full prescribing details.

19

Upward
and onward*
Supporting platelets and patients for more than 15 years
WinRho SDF [Rho(D) Immune Globulin Intravenous (Human)] has a safety and
tolerability profile established in clinical trials and 15 years of use
In a pivotal trial (N=146), there was no significant difference in response rates
between WinRho [Rho(D) Immune Globulin (Human) for Injection] (84.2%),
low-dose IVIG (90.0%), or high-dose IVIG (93.1%)1,2
In children with chronic ITP, a response rate of 79% was observed with WinRho1,2
The mean duration of response in children with chronic ITP was 36.5 days1
WinRho SDF Liquid Is Bioequivalent to WinRho SDF Lyophilized1

In two comparative pharmacokinetic studies (N=101), the formulations were bioequivalent following IV
administration based on the area under the curve to 84 days and had comparable pharmacokinetics
following IM administration. Both formulations also had similar elimination half-lives. WinRho SDF
must be administered via the intravenous route for the treatment of ITP.

*Patient results may vary.

Study performed using WinRho. Patients received WinRho 25 g/kg on days 1 and 2; IVIG 1.0 g/kg on days 1 and 2; or IVIG 0.8 g/kg on day 1.
Response defined as an increase in absolute platelet count to >50,000/mm3.

Study performed using WinRho administered in a dose range of 25 to 55 g/kg. Response defined as doubling of pretreatment platelets with counts
>50,000/mm3. Duration of response defined as days from administration of last infusion to the occurrence of first platelet count <15,000/mm3
over baseline levels or to end of observation period.

Study performed using WinRho administered in a dose range of 25 to 55 g/kg. Duration of response defined as days from administration of last infusion
to the occurrence of first platelet count <15,000/mm3 over baseline levels or to end of observation period.

References: 1. WinRho SDF Prescribing Information, December 2010. 2. Data on file, Cangene Corporation

Please see Important Risk Information

and Boxed Warning on pages 18-19.
Please see accompanying full Prescribing
Information for full prescribing details.

bioPharma
WinRho SDF is a registered trademark of Cangene Corporation.
Distributed by Cangene bioPharma, Inc. Manufactured by Cangene Corporation.
2011 Cangene Corporation. All rights reserved. CBI-WR-PLLBK-2011-02