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Iron Chelation Amongst

Thalassaemics : A need

for reappraisal

Thalassaemia Daycare Clinic, Hospital Tuanku Fauziah

Paediatric DepartmentHospital Tuanku Fauziah


Introduction

Thalassaemia is the commonest haemoglobin (blood) disorder in Malaysia total thalassaemics in Malaysia – 4292

Malaysian Thalasaemia registry, 2008

Transfusion dependent thalassaemics need regular blood transfusion for survival. regular blood transfusion causes iron overload in the body.

Iron overload causes multiple organ damage which lead to morbidity and mortality.

Gary M. Brittenham, N Engl J Med 1994, 331:567-573

Without blood transfusion, transfusion-dependent patient usually only survived first decade of life. With transfusion, the life expectancy increased to 2nd or 3rd decade of life, but with regular transfusion and iron chelators, patient can have normal life expectancy.

Iron overload can be

minimized by iron

chelators

Desferrioxamine

Deferiprone

Iron overload can be

measured by :

Clinical

Serum ferritin level

Liver biopsy

Radiological (MRI T2*)

Paediatric Department

Hospital Tuanku Fauziah

Desferrioxamine

Deferiprone

Metal

Deferiprone

Alternative iron chelators

Oral

Tds dosing, daily

Side effect :

Agranulocytosis,arthropat

hy, GIT side effect.

Desferrioxamine

Subcutaneous injection

5 days per week

8 to 12 hrs infusion.

Delivered via battery operated infusion pump

Side effect : allergy, vision and hearing impairment,

growth retardation

Chelator MetalOutside

the

body+ ChelatorIron

chelators



Initiation of iron chelators in Northern hospital

Hospital Tuanku Fauziah 24/96 (25%)

Hospital Pulau Pinang 66/143 (46%)

Hospital Sultan Abdul Halim 23/89 (25%)

Hospital Seberang Jaya 43/142 (30%)

Clinical Research Centre, Hospital Pulau Pinang,2008


Opportunity Statement

Iron overload in thalassaemic patient is a critical

issue.

Iron overload causes damage of multiple organs

and cause morbidity and mortality.

Identifying the causes for patient not using or

comply to medication will enable us to

implement necessary measures.

Use of iron chelator with good compliance will

improve quality of life and longer survival.


Hospital Tuanku Fauziah

Factors For Not Initiating Iron Chelators in

Thalassaemia

Not initiated

of iron

chelators

Untrained in

use of infusion

pumps

Uncoordinated &

non-systematic

management

Non

continuous

supply

Less

patient’s self

worth and

motivation

Untrained and

skilled

personnel

Less

knowledge

Insufficient

funds

Undedicated

personnel

Non-

adherence to

management

protocol

Less family and

community

support

Lack knowledge

on objective of

treatment

Thalassaemia

budget for

2008 for HTF :

RM 400000


Thalassaemia

Clinic

Workflow

Thalassaemia

Day Care Clinic

Follow up

Transfusion

regimeHypotransfusion Hypertransfusion

Need for

chelation

Yes No

Continuous

monitoring and

assessment

Follow up

Chelation

therapy started


Process of Starting Chelation Therapy

Hypertransfused

Thalassaemics

•Age > 3 years old

•Has received 10 – 20 blood transfusions

•Serum Feritin level > 1000 mcg/L

Yes No

Chelation

therapy started

Reviewed by

specialist Continuous

monitoring and

assessment


Model of Good CareSTEP PROCESS OF CARE CRITERIA STANDARD

1. Individualized follow-

up Procedures

a) Counselling

i) by specialist

ii) at first visit, upon starting

iron chelation, when not

compliant

iii)for patient and caretaker

b) Serum ferritin 6 monthly

100%

100%

2. Good knowledge of

staff

a) >80% score on

questionnaire.

b) Trained in technique of

desferrioxamine injection.

100%

100%


STEP PROCESS OF CARE CRITERIA STANDARD

3 Supervision at each

clinic visit

a) By specialist or senior MO 100%

4. Iron chelation therapy a) Therapy started for

i) patient age more than 3

yrs

ii) serum ferritin more than

1000 gm/L

iii) transfused 10-20 times

b) Demonstration of desferal

infusion technique

i) by trained staff

ii) handbook and cd given

iii) desferioxamine starter

kit given

c) Monitoring of side

effect/technical difficulties

each clinic visit.

100%

100%

100%


STEP PROCESS OF CARE CRITERIA STANDARD

5. Supply of medications

and related items

a) Related items are supplied

according to a checklist.

b) Desferioxamine supplied on

exchange basis.

100%

100%

6. Home monitoring a) Patient filled up home

monitoring record daily.

b) Home record checked

monthly by MO/ specialist.

100%

100%


Study Design

Phase 1A verification

study

From 1/7/2006

to 30/9/2006

3 months

Cross

sectional cohort

Phase 2Reevaluation

From 1/9/2007

to 30/11/2007

3 months

Interventions

•From November

2006 to August 2007

•10 months



Objectives

General

To improve numbers of patient on iron chelators and their compliance

Specific

To measure the magnitude of the patient not initiated on iron chelators and their compliance

To identify the possible causes for not initiated on iron chelators

To identify the possible causes non-compliance to iron chelation therapy

To formulate and institute remedial measures to increase usage of iron chelators, and ensuring compliance

To evaluate the effectiveness of the remedial measures


Indicators and Standard

Indicator:

Percentage of thalassaemia patients initiated on iron chelation therapy

Total number of thalassaemia

patients on iron chelation therapy

Total number of thalassaemia

patients fulfilling criteria for

starting iron chelation therapy

X 100%

Standard: >80% chelated


Indicators and Standard

Indicator:

Compliance rate of thalassaemia patient on iron chelation

therapy

Number of patients compliant to

treatment

Number of patients chelatedX 100%

Standard: >60 % compliance


Inclusion Criteria

All Thalassaemia patients that;

Have received 10 – 20 blood transfusions

Serum ferritin level > 1000 mg/L

Age > 3 years

Exclusion :

Patient allergic to medication

Contraindicated for desferrioxamine/deferiprone

Compliance :

Patient considered compliant when

Mean usage of desferrioxamine more than 4

days per week

Mean intake of deferiprone 2 times or more

daily.

Hospital Tuanku FauziahPaediatric Department


Methodology – Phase 1

Aim : To measure the magnitude of the patient not on iron chelators and their non compliance, and the reasons for it.

Place : Thalassaemia Clinic

Duration : 3 months (1st July 2006 – 30th Sept 2006)

Sample : 45 patients

Study instrument :

Questionnaires, invidualized patients folders, iron chelation usage chart, clinic log book, counseling log book, serum ferritin level.

Phase 1 : findings


Phase 1 findings

Patient

indicated

for

chelation

Chelated

Not chelated

Desferrioxamine

Deferiprone

Non compliant

Non

compliant

n=45

n=24

n=21

(47%)

n=22

n=2

18/22

(81%)

2/2

(100%)

4/22

compliant

0/2

compliant

Total

thalassaemia

patient

9696


0

1

2

3

4

5

Mean

days o

f in

jecti

on

/week

Patient (n=22)

compliant

Non complaint


Patients’ compliance to desferrioxamine

0

1

2

nu

mb

er

of

pati

en

t

1 2 3

Frequency of deferiprone intake/day

1 1

Patients’ compliance to deferiprone

0


Reasons for not initiating iron chelation

No of patient %

(n=21)

Fear of pain 13/21 (60%)

Inconvenience 12/21 (55%)

Monetary problem 12/21 (55%)

Difficult procedure 11/21 (50%)

Poor motivation 8/21 (40%)

Ignorance 4/21 (20%)

Intolerable side effect 0/21 ( 0%)


Reasons for not complaint to iron chelation

No of patient %

(n=20)

Fear of pain 19/20 (95%)

Monetary problem 19/20 (95%)

Inconvenience 15/20 (75%)

Poor motivation 14/20 (70%)

Difficult procedure 12/20 (60%)

Intolerable side effect 2/20 (10%)


Questionnaire and training for staff

Staff Score on questionnaire

(passing mark > 80%)

Desferrioxamine

preparation and injection

Impression

a 100% Yes Trained

b 98% Yes Trained

c 95% No Not trained

d 98% No Not trained

e 90% No Not trained

f 79% Yes Not trained

g 76% No Not trained

h 75% No Not trained

i 69% No Not trained

j 50% No Not trained

k 65% No Not trained

Staff considered trained when score > 80% on questionnaire and has

hands on skill on preparation and injection of desferrioxamine


Interventions


Reducing pain

Butterfly needle : 23 GThumb tack : 29 G

Reduce

needle

size

Local anesthetic

60 % of patient not

started on iron chelation

and 95 % non

compliance due to

pain


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Desferal User

Manual

Difficult procedure made easy

50% of patient not starting and

60 % of patient non

compliance due to difficult

procedure


Desferrioxamine manual CD


Desferrioxamine Starter Kit



Thalassaemia Workshop for Desferrioxamine Users


Thalassaemia Motivation Talk

Increase awareness and improves motivation

•20 % of patient doesn’t

know they need to use

iron chelator

•Up to 70 % admit that

they are not motivated to

use iron chelator

Improved awareness and

motivation increased

compliance


Counseling sessions by specialist

Patient must have all the information they

need : disease, treatment, long term

implication


Home visit

Calling patient

Thalassaemia

liaison nurse

Developing relationship between

patient and healthcare team

Psychosocial support with

people who loves them


Patient-held Record Book- for home-based monitoring

Ultimately patient must take large degree of responsibility for

compliance

Ferritin level

stated in patient

handbook

Constant

reminder

improved

compliance



Role Model : the success story

Isn’t he

looking well ?

Must have

been

compliant…..


Compliance Monitoring

Supply of medications on exchange basis

Log book - Record of amount and frequency

medications supplied to each patient


Staff Education and Training

Core staffs sent for courses/seminars in

management of Thalassaemia

Questionnaire and hands on skill on preparation

of desferrioxamine

CME sessions

Contents:

Basic knowledge of the disease, diagnosis, natural

history, management and complications

Importance of adherence to management protocol


Local Management Protocol

- for use in Thalassaemia Clinic, HTF

Changing iron chelators

1 deferiprone

user converted

to

desferrioxamine

due to

intolerable side

effect

2 desferrioxamine

user converted to

deferiprone due to

not tolerating pain

and long infusion

hour



New Work

Process Thalassaemia Clinic

Workflow

Thalassaemia

Follow up

Counseling

Transfusion

regimeHypotransfusion Hypertransfusion

Counseling

Need for

chelation

Yes No

Follow upNew

New

Chelation

therapy started

Continuous

monitoring and

assessment


New Work

Process Starting Chelation

Therapy

Hypertransfused

Thalassaemics

•Age > 3 years old

•Has received 10 – 20 blood transfusions

•Serum Feritin level > 1000 mcg/LYes No

Chelation

therapy started

Reviewed by

specialistContinuous monitoring

& assessment

Compliance Continuous monitoring &

assessment

Counseling

Yes

No

ComplianceYesConsider

change type of

chelator

No

New

New

New

New

Interventions

Reasons not

starting/non compliant

Aim Interventions

Fear of pain Reduce Pain Local anaesthesia

Thumb tack

ADL disturbed Motivation Motivational talk

Peer support

Role model

Difficult procedure Correct technique Demonstration

User manual

Compact Disc

Monetary problem - Provided by KKM

Ignorance Improving awareness Continuous monitoring

MO in charge

Counselling by specialist

Poor motivation motivation Thalasemia liaison nurse

Home based monitoring

Home visit

Motivational talk

Intolerable side effect Other chelator option


Methodology - Phase 2

Aim : To assess effectiveness of

interventions

Place : Thalassaemia Clinic

Duration : 3 months (1st September 2007 –

30st November 2007)

Sample : 44 patients, 1 dropout (death)

Study instrument :

Special form, interviews, questionnaires

Evaluation of data in log book : which records amount and

frequency of medications supplied to each patient

Evaluation of individual patient’s home-based record book

:relies on patient’s truthfulness

Phase 2 : findings


Phase 2 findings

Chelated

Not

chelated

Total

patient

indicated

n=44

n=21

n=24

Chelated

n=40

Not chelated

n=39

n=5

Pre

intervention

Post

intervention


Phase 2 findings

Patient

chelated

desferrioxamine

deferiprone

compliant

Non

compliant

n=39

n=37

n=2

n=27

n=10

n=28

n=8

n=1n=3

n=1

n=0

compliant

Non

compliant

1 convert to

desferrioxami

ne

compliant

Non

compliant

compliant

Non

compliant

2 convert to

deferiprone

+1

+2

0

1

2

3

4

5

Mean

days o

f in

jecti

on

/week

Patient (n=36)

compliant

Non complaint

Pre intervention Post intervention

Patients’ compliance to desferrioxamine

Patient (n=22)


3

0

1

2

3

1 2 3

pre intervention post intervention

Frequency of deperiprone intake/day

Nu

mb

er

of

pati

en

tPatients’ compliance to deferiprone

1

0

1

0 0

3


Questionnaire and training for staff

Staff Score on questionnaire

(passing mark > 80%)

Desferrioxamine

preparation and injection

Impression

a 100% Yes Trained

b 98% Yes Trained

c 99% Yes Trained

d 98% Yes Trained

e 95% Yes Trained

f 88% Yes Trained

g 90% Yes Trained

h 95% Yes Trained

i 96% Yes Trained

j 87% Yes Trained

k 88% Yes Trained

Staff considered trained when score > 80% on questionnaire and has

hands on skill on preparation and injection of desferrioxamine



Model of Good CareSTEP PROCESS OF

CARE

CRITERIA STANDARD PRE

INTERVEN

TION

POST

INTERVE

NTION

1. Individualized

follow-up

Procedures

a) Counselling

i) by specialist

ii) at first visit, upon starting iron

chelation, when not compliant

iii)for patient and caretaker

b) Serum ferritin 6 monthly

100%

100%

53%

75%

85%

95%

2. Good

knowledge of

staff

a) >80% score on questionnaire.

b) Trained in technique of

desferrioxamine injection.

100%

100%

45%

27%

100%

100%


STEP PROCESS OF

CARE


INTERVEN

TION

POST

INTERVEN

TION

3 Supervision at

each clinic visit

a) By specialist or senior MO 100% 49% 100%

4. Iron chelation

therapy

a) Therapy started for

i) patient age more than 3 yrs

ii) serum ferritin more than

1000 gm/L

iii) transfused 10-20 times

b) Demonstration of desferal

infusion technique for

indicated patient

i) by trained staff

ii) handbook and cd given

iii) desferioxamine starter kit

given

c) Monitoring of side

effect/technical difficulties

each clinic visit.

100%

100%

100%

53%

New

intervention

60%

89%

100%

100%


STEP PROCESS OF

CARE


INTERVEN

TION

POST

INTERVEN

TION

5 Supply of

medications

and related

items

a) Related items are supplied

according to a checklist.

b) Desferioxamine supplied on

exchange basis.

100% New

intervention

100%

6. Home

monitoring

a) Patient filled up home

monitoring record daily.

b) Home record checked monthly

by MO/ specialist.

100%

100%

New

intervention

New

intervention

90%

100%

0

10

20

30

40

50

60

70

80

90

100


not chelated chelated%

Perc

enta

ge o

f patient Standard >

80%

47 %53 %

11 %

89 %

Patients’ initiation on iron chelation


0

10

20

30

40

50

60

70

80

90

100


not compliant compliant%

Perc

en

tag

e o

f p

ati

en

t

Standard >

60%

83 %

17 %21 %

79 %

Patients’ compliance on iron chelation


Mean changes in serum ferritinM

ean c

hanges in s

eru

m f

err

itin

(μ

g/L

0

-1000

-2000

-3000

-4000

+1000

+2000

+3000

Desferrioxamine DeferriproneNot chelated

Non compliant

compliantcompliant



Conclusion

There is an increment in percentage of

Thalassaemics chelated to 89%

Standard achieved

Compliance rate improved to 79%

Standard achieved

Compliance rate is further improved by

changing the type iron chelator used

78% compliance rate with Deferrioxamine users

100% compliance rate with deferiprone users

There is better acceptance and compliance by

using oral iron chelating agent

Post intervention : reason for not starting/ non compliance to iron

chelation

Not starting n= 5 Non compliance n=8

Fear of pain 1/5

ADL disturbed 3/5 4/8

Difficult procedure

Monetary problem

Ignorance

Poor motivation 4/5 6/8

Intolerable side effect

Analysis of patient not initiated and not compliant to iron

chelation after intervention



Next Step

Step 1 Step 2 Step 3

To increase the

number of

Thalassaemics

chelated

To ensure

compliance to

iron chelation

therapy

To maintain

and further

improve the

standards that

has been

established

and achieved


References

Guideline For Management of Thalassaemia

Patients; KKM CPG 2005

About Thalassaemia; Dr A. Eleftheriou;

Thalassaemia Int. Federation; 2003

Standards for the Clinical Care of Children &

Adults with Thalassaemia in the UK; UK

Thalassaemia Society; 2005

Paediatric Protocols for Malaysian Hospitals;

Hussain Imam, Ng H.P.; MOH; 2005


References

Alireza AS, Mir Reza B, Mohamad K, et.al:

Metabolic and endocrinologic

complications in beta thalassaemia major:

a multicenter study Tehran.

BMC Endocrine Disorders 2003, 3:4

Kwan EY, Lee AC, Li AM, Tan SC, Chan CF,

Lau YL, Low LC: A cross-sectional study of

growth, puberty and endocrine function in

patients with thalassaemia major in Hong

Kong.

J Paediatr Child Health 1995, 31:83 - 7


References

Olivieri NF, Nathan DG, MacMillan JH, Wayne

AS, Liu PP, McGee A, Martin M, Koren G,

Cohen AR: Survival in medically treated

patients with homozygous beta

thalassaemia.

N Engl J Med 1994, 331:574 – 578

C Burgna Pignatti, MD Cappelini, P DeStefans,

G C Del Vecchio, G L Forni, M R Gamberini, R

Ghilard, R Origa, A Piga, M A Romeo, H Zhao

and A Cnaan: Survival and complications in

thalassaemia.


References

Gary M. Brittenham, Patricia M. Griffith, Arthur

W. Nienhuis, Christine E. McLaren, Neal S.

Young, Eben E. Tucker, Christopher J. Allen,

David E. Farrell, and John W. Harris: Efficacy

of Deferoxamine in Preventing

Complications of Iron Overload in Patients

with Thalassemia Major.

N Engl J Med 1994, 331:567-573


Gantt ChartActivit

y

Re

sp

on

sibi

lity

May Jun Jul

y

Aug Sep

t

Oct Nov Dec Jan Feb Mar Apr May Jun Jul

y

Aug Sep

t

Oct No

v

Com

mittee

briefin

g

Dr.

Ja

ma

l

Plann

ing

Dr.

Nu

r

Staff

briefin

g

Dr.

Nu

r

Data

collec

tion

G

M

Data

analy

sis

G

M

Reme

dial

action

G

M

Re-

evalu

ation

G

M

Repor

t

writin

g

G

M

Planned

Actual



SMART criteria

SThalassaemic those who are on frequent transfusions will

have iron overload that causing morbility and morbidity

MBased on case records at Thalassaemia Clinic and

ongoing investigation and physical examinations.

A To make sure thalassaemic will have longer life span

RTreatment available to treat this iron involvement.

T

Health conscious and the it is the right time for intervention

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