newsletter from all eights iii.pdf · newsletter from all eights announcing launching of evolution...

Newsletter from All Eights

� Announcing Launching of

Evolution Expert Series and ABX

Pentra DX120+SPS Evolution

Newsletter from All Eights

� Review of Haemos

& Workshop

� Haemostasis Workshop: Questions

and Answers

� Validation of INR and Calibration of

PT/INR

� Comparison of a

commercial Pool Norm

Announcing Launching of STA-R

Expert Series and ABX

Pentra DX120+SPS Evolution

Review of Haemostasis Symposium

Haemostasis Workshop: Questions

of INR and Calibration of

Comparison of a home made and a

commercial Pool Norm

Editor’s Editor’s Editor’s Editor’s columncolumncolumncolumn

Dear readers,

Warm greetings and a hearty welcome to the Guide to Haemostasis Newsletter. We trust that the

information contained in this edition will be just as interesting as the previous editions.

Recently, we concluded the Haemostasis Symposium & Workshop held on 24 – 25 June 2009 at

the Shangri-La Hotel, Kuala Lumpur. Collaborated between Hemophilia Society of Malaysia,

Diagnostica Stago and All Eights, the event had renowned local and overseas presenters shared

their views on Paediatric Haemostasis. The workshop was conducted by experts in the field of

Accreditation and Quality Assurance. We are happy that the event was a great success and have

included highlights in this issue.

In the section on application, the workshop leaders present and answer questions posed during

the sessions. Dr Wan Zaidah Abdullah from Hospital Universiti Sains Malaysia wrote an excellent

paper on validation of INR and calibration of PT/INR. Prof Madya Dr Leong Chooi Fun shared

some of the questions asked during the workshop. From the Info Counter, our specialist

answered some frequently asked questions that you may find it helpful when handling your STA

line coagulation analyzer. There is also a Bulletin Corner which includes our Application Team

activities.

Lastly, we are proud to announce that All Eights will be organizing the launching of Stago high-

end coagulation analyzer – the STA-R Evolution Expert Series. We will be launching the system

together with Horiba Medical Hematology analyzer – ABX Pentra DX120 + SPS Evolution. The

event will be held at Sheraton Imperial Hotel, Kuala Lumpur on 19 November 2009.

We hope you all will enjoy this newsletter as much as we have enjoyed making it. We would like

to extend our deepest gratitude to both Dr Wan Zaidah Abdullah and Prof Madya Dr Leong Chooi

Fun for making both the workshops and our newsletter a success.

Best wishes,

Editorial team

Focus

Review of Haemostasis Symposium & Workshop

Application

Validation of INR and Calibration of PT/INR

Questions and Answers from the Haemostasis Workshop

Info Counter

Bulletin Corner

Information Update

STA-R Evolution – Expert Series

Launching of STA-R Evolution

Monitoring Heparin Therapy

ContentsContentsContentsContents

Review of Haemostasis Symposium & Workshop

Calibration of PT/INR

Questions and Answers from the Haemostasis Workshop

Information Update

Expert Series

R Evolution

Monitoring Heparin Therapy

ContentsContentsContentsContents

2

6

Questions and Answers from the Haemostasis Workshop 10

13

14

16

17

19

Focus 2

The Haemophilia Society of Malaysia, All Eights (Malaysia) Sdn Bhd and

Diagnostica Stago, France, jointly collaborated to organize a Haemostasis

Symposium & Workshop on the 24th

and 25th

June 2009 at the Shangri-La

Hotel, Kuala Lumpur.

It is a fact that children and adults do not share the same normal ranges for

haemostasis. The symposium introduced the participants to methods used

to establish paediatric ranges as well as some clinical haemostasis

disorders in children. Another important topic covered in the workshop is

accreditation for laboratory haemostasis investigations. As we strive to

achieve ISO 15189 Standards, we must look beyond accreditation for

clinical chemistry and hematology disciplines to include accreditation for

haemostasis testing as this topic also plays a vital role in the steps and

protocols towards ISO 15189.

More than 140 delegates from more than 50 institutions / organizations

participated in the symposium and workshop. Both local and international

speakers were invited to present during the 2-day event. Renowned

presenters include Cik Faridah Bt Md Afandi, Head of Haemostasis Unit at

the National Blood Centre; Dr Nicole Schlegel from Robert Debré Hospital

in Paris; Dr Jameela Sathar, Consultant Haematologist at Hospital Ampang;

Dr Vera Ignjatovic, Head of Laboratory Research Department of Clinical

Haematology at the Royal Children’s Hospital, Melbourne, Australia; and Dr

Patricia Roger, Reagent Product Manager from Diagnostica Stago, France.

The workshop facilitators were Prof Madya Dr Leong Chooi Fun, Consultant

Haematologist from Pusat Perubatan Universiti Kebangsaan Malaysia; Dr

Wan Zaidah Abdullah, Haematologist from Hospital Universiti Sains

Malaysia; Pn Aini-Ardena Mustapha from Pusat Perubatan Universiti

Kebangsaan Malaysia and Pn Wan Soriany Bt Wan Md Zain from Hospital

Universiti Sains Malaysia.

President of Haemophilia Society of Malaysia, Dato’ Dr Faraizah Bt Dato’ Hj

Abdul Karim, launched the symposium with a heart-felt welcome speech.

The morning session was chaired by Dr Roshida Bt Hassan, Head of

Hematology Unit from Hospital Kuala Lumpur. She introduced the first

speaker, Cik Faridah Md Afandi who gave a presentation on “Review of

current Haemostasis and Thrombosis in Malaysia”. She explained the role

of the Haemostasis Laboratory at the National Blood Centre as a referral

centre for the diagnosis of bleeding disorders and thrombophilia screening

in Malaysia and covered some statistics for haemorrhagic disorders.

Haemostasis Symposium & Workshop

Dr Nicole Schlegel shared her views and experiences in Thrombosis and Thrombophilia in children.

She briefly discussed about the causes, acquired or inherited or both, which may be associated

with the development of Venous Thromboembolism (VTE) in the paediatric population.

After the morning tea refreshment, Dr Jameela Sathar presented “Haemostasis in Neonates”.

According to Dr Jameela Sathar, physiologically immature haemostatic system in the newborn

may contribute to significant morbidity in the sick and premature infant. In order to manage the

haemostasis disorders in newborn, it is important to understand the changing patterns of

coagulation parameters during fetal development and to know how the normal values at birth

differ from adults.

“Haemostasis reference ranges are age-dependent, changing constantly immediately post-birth

and throughout early childhood”, says Dr Vera Ignjatovic in her talk on ‘The Importance of Age

Appropriate Haemostasis Reference Ranges”. In her research, Dr Vera Ignjatovic has established

reference ranges for healthy neonates and children in Australian population. These results

confirmed that population, reagent and analyzer specific testing are critical for adequate clinical

decision making.

The afternoon session was chaired by Professor Cheong Soon Keng from International Medical

University, Malaysia. Dr Nicole Schlegel continued with a second presentation on “Platelet

disorders in children” which are the consequences of different mechanisms, either acquired or

inherited. She stated that most common platelet disorder in children is thrombocytopenia. This

was followed by Dr Vera Ignjatovic’s presentation on “Heparin Therapy in Children”. She discussed

about the importance of monitoring Unfractionated Heparin (UFH) therapy due to its relatively

narrow therapeutic window. The American College of Chest Physicians (ACCP) produced evidence-

based recommendations regarding the management of anticoagulant therapy, including UFH.

Focus 3

Focus 4

As anticoagulation therapy is used extensively nowadays, Dr Patricia Roger presented on

“Outpatient Management of Anticoagulant Therapy” during the symposium. The current

mainstays of treatment are heparin or heparin-like drugs and oral warfarin. Stago offers a

wide range of adapted reagent to monitor this treatment such as Anti-Xa assays and PT

determination. The symposium ended by having a feedback forum with All Eights and Stago.

The second day event began with some short-morning lectures. Dr Jamilah Baharom gave a

lecture on ISO 15189, and brief explanation regarding the requirements. She highlighted a

few points to ensure the quality of test performance and the reliability of patients’ test

results. Dr Jamilah Baharom emphasized the importance to improve continuously in order to

achieve the objectives of quality management system. Dr Patricia Roger gave a short

presentation on Laboratory Diagnosis of Lupus Anticoagulant. She introduced and explained

on Stago reagents for LA testing and Pool Norm for mixing study. Besides the LA diagnosis,

she also talked on the role of IQC and EQA in laboratory performance.

The primary objective of the workshops is to understand and implement the methods

required for validation of PT/INR systems and APTT sensitivity to coagulation factors and

heparin (UFH). Its secondary objective is to recommend the strategies and actions needed

following the results obtained from the validation procedure. There were 4 workshop

stations, each fully armed with 4 units of STA-Compact, fully automated coagulation analyzer

and 4 experienced Technical Application Specialists to assist the workshop facilitators.

This symposium and workshop was a great opportunity for the participants to further their

knowledge and experience in haemostasis. The success of this symposium and workshop

warranted the need for more similar events in near future.

Team work

Team work

Validation of INR and Calibration of PT/INR

Dr Wan Zaidah Binti Abdullah, Hospital Universiti Sains Malaysia

This article describes one approach for validation and

calibration of INR test based on approved guideline

from Clinical and Laboratory Standards Institute (CLSI).

There are probably other methods (or modified

methods) that can reliably be used to verify/calibrate

the PT/INR test based on experience or other different

guidelines.

The importance of performing a “checking system” on

INR/PT test is mainly due to safety issue related to

therapeutic ranges for patients on vitamin K antagonist

(VKA) and to reliably report the results of haemostatic

status of the patients. There are two main guidelines

from CLSI (see references 1 and 2 below) addressing the

procedures to guide all medical laboratories to achieve

the acceptable practice of quality assurance activities

related to PT/INR test. In the Specific Criteria 2 from ISO

15189 document on clause 5.6 for assuring quality of

examination procedures, there is a statement:

“..programme for calibration of measuring systems and

verification of trueness shall be designed and

performed…….” This statement is applicable to the

verification of INR in order to prove the test system is at

the acceptable standard.

There are a few important glossaries3 in the

understanding of INR validation/verification procedure

as noted below:

The basic formula for INR calculation:

�� ISI

� Calibration plasmas (CP) or certified plasmas:

plasmas to which INR values have been assigned

using an approved method. CP can be used for

verification and also for calibration of ISI/INR test.

� Calibration: The process of establishing a

relationship between values as measured by the

system in question and values determined using a

standard, applied here for the process of

calibrating a test system for an ISI.

X � Antilog �� /"#

� Mean normal PT (MNPT): The geometric mean of

the PTs of the healthy adult population (for

practical purposes, the geometric mean of PT is

calculated from 20 samples from healthy

individuals, including both sexes, is reliable for

approximation of MNPT). It is important to stress

that the recommended calculation for MNPT is

done by using geometric mean and not by the

usual arithmetic mean. The skewness of PT values

can be compensated for by using the geometric

mean. The correct MNPT is critical in determining

the accuracy of INR. The calculation can be easily

done by using statistic calculator available from

the website or by computer-based statistical

programme. The mathematical formula for

geometric mean as shown below:

� International sensitivity index (ISI): A quantitative

measure/mathematical indicator of the

responsiveness of a PT testing system to the

defect induced by VKA therapy/warfarin. There

are two types of ISI: Generic ISI (not specific for PT

reagent-instrument type) and reagent-instrument

specific ISI.

� Verification/validation: A secondary procedure to

confirm a calibrated value, this is considered as

necessary within the process of generating valid

ISI and MNPT values.

Although some manufacturers provide assigned ISI

values for specific PT reagents and instrumentation, it

is still recommended practice that laboratories check

or locally validate these ISIs, as well as determine

laboratory own MNPT based on the local population

being tested. Local ISI may vary from the

manufacturer determined thromboplastin/instrument

specific ISI because ISI values often vary between

instruments and between models even of the same

brand 2.If generic ISI from PT reagents is used, the

validation procedure is strongly recommended as

stated in the CLSI guideline.

Application 6

Current recommendations suggest the use

plasma (CP) calibration sets to verify the ISI of PT

reagents and for calibration procedure

further verification checks should be performed prior

to acceptance of ISI and MNPT estimates generated

from commercial CP sets. The methods

verification and calibration are described below.

There are a few steps to follow on this verification and

calibration procedure. Although the methods outlined

in the guidelines provide a promise for reliable INR

results, the process does not compromise the need to

enroll in the inter-laboratory comparison exercise

external quality assurance (EQA) programme.

The first step in the verification process is to verify the

ISI values given by the manufacturer are correct for the

laboratory reagent-instrument system (for both types

of generic and specific ISI). This can be achieved by

using the CP. Usually a set of CP from four different

levels of INRs are used for this purpose. By using the

laboratory own MNPT and PT results from the reagent

and ISI value from the manufacturer, the INR can be

generated for this set of CPs. The INRs obtained should

be within acceptable ranges (ie +/- 15% of the assigned

CPs’ INRs) for all the levels. If this INR obtained locally

does not fall within this range, a next step is to

calibrate the system and develop the laboratory own

ISI value for INR calculations. Whilst if the INRs

obtained for the CPs are within the ranges mentioned

above (+/- 15% of the assigned CPs’ INRs), there is no

need to do local calibration of ISI. Hence, the ISI

provided by the manufacturer and laboratory own

MNPT value are acceptable for use of INR calculation

and valid for reporting. The INR results should be

monitored continuously together with participation in

EQA to ensure provision of correct results are

sustainable.

When the CPs’ INR results are not within 15% of the

assigned CPs’ INR (for all CPs), the laboratory should

review the value of MNPT used to calculate INR. The

MNPT should be correctly calculated as described

above. If the value of MNPT is correctly assigned then

calibration of the system is required. In this calibration

step, CP set is alternatively used to calculate a local

(laboratory own) ISI. When one CP

provide/calibrate an ISI estimate, and sometimes also

an estimate for MNPT, such estimates must be verified

Application

suggest the use of certified

to verify the ISI of PT

reagents and for calibration procedure. However,

further verification checks should be performed prior

to acceptance of ISI and MNPT estimates generated

The methods for the

verification and calibration are described below.

on this verification and

calibration procedure. Although the methods outlined

in the guidelines provide a promise for reliable INR

romise the need to

laboratory comparison exercise4 or

external quality assurance (EQA) programme.

The first step in the verification process is to verify the

ISI values given by the manufacturer are correct for the

instrument system (for both types

of generic and specific ISI). This can be achieved by

P from four different

levels of INRs are used for this purpose. By using the

laboratory own MNPT and PT results from the reagent

and ISI value from the manufacturer, the INR can be

generated for this set of CPs. The INRs obtained should

15% of the assigned

CPs’ INRs) for all the levels. If this INR obtained locally

does not fall within this range, a next step is to

calibrate the system and develop the laboratory own

ISI value for INR calculations. Whilst if the INRs

ned for the CPs are within the ranges mentioned

15% of the assigned CPs’ INRs), there is no

need to do local calibration of ISI. Hence, the ISI

provided by the manufacturer and laboratory own

MNPT value are acceptable for use of INR calculation

and valid for reporting. The INR results should be

monitored continuously together with participation in

EQA to ensure provision of correct results are

When the CPs’ INR results are not within 15% of the

laboratory should

review the value of MNPT used to calculate INR. The

MNPT should be correctly calculated as described

above. If the value of MNPT is correctly assigned then

In this calibration

used to calculate a local

CP set is used to

an ISI estimate, and sometimes also

an estimate for MNPT, such estimates must be verified

(validated) after determination of the local ISI

a different lot of CP set

manufacturer2. Calibration and validation must never

be performed by using the same manufacturer lot of

and it is also be preferable to use an alternative

manufacturer product

remember that validation of the newly assigned ISI by

the laboratory must be done separately.

The calculation on how to

(usually 4 different INRs) can be done easily by using

the software for ISI measurement. Alternatively ISI can

be calculated by using manual graphical analysis.

Manufacturer of CP products could help in the ISI

calculation by using the software as this is best

explained by hands-on practical session. The method of

calculating ISI has been modified from the original

WHO recommendation. In the last Haemostasis

Workshop for STAGO users, ISI calculation from this CP

set was demonstrated. The manufacturers of PT

reagents also provide ‘helps’ to their customers to

calculate the ISI and/or MNPT (if required). The

example of the template (using software) for ISI

calibration and its calculation is shown in figure 1.

Participation in EQA is also included as part of the

verification process to ensure the INRs determine by

the laboratory own ISI/ PT system are accurate and

sustainable.

When the INR calculation using laboratory own ISI

value are in agreement with the assigned INRs of the

CP set, ie within of the assigned CPs’ INRs, the ISI

determined by the laboratory is valid for reporting of

INR. On the other hand, if the new estimate ISI fails

(not within +/- 15% of the assigned INR), the ISI is not

valid for reporting the INR. It should be

that for verification of the ISI estimated by the

laboratory, the CP set for verification should be

different from the one used for the local calibration of

ISI. Causes of failure of local ISI calibration need to be

sought out immediately a

experts are required. Summary on the recommended

actions to take when failed to establish local ISI are

described below.

after determination of the local ISI by using

set or using CP from another

Calibration and validation must never

using the same manufacturer lot of CP

also be preferable to use an alternative

if available. It must be

remember that validation of the newly assigned ISI by

the laboratory must be done separately.

The calculation on how to derive ISI from a set of CP

(usually 4 different INRs) can be done easily by using

the software for ISI measurement. Alternatively ISI can

be calculated by using manual graphical analysis.

Manufacturer of CP products could help in the ISI

ing the software as this is best

on practical session. The method of

calculating ISI has been modified from the original

WHO recommendation. In the last Haemostasis

Workshop for STAGO users, ISI calculation from this CP

ted. The manufacturers of PT

reagents also provide ‘helps’ to their customers to

calculate the ISI and/or MNPT (if required). The

example of the template (using software) for ISI

calibration and its calculation is shown in figure 1.

also included as part of the

verification process to ensure the INRs determine by

the laboratory own ISI/ PT system are accurate and

When the INR calculation using laboratory own ISI

value are in agreement with the assigned INRs of the

et, ie within of the assigned CPs’ INRs, the ISI

determined by the laboratory is valid for reporting of

INR. On the other hand, if the new estimate ISI fails

15% of the assigned INR), the ISI is not

valid for reporting the INR. It should be stressed again

that for verification of the ISI estimated by the

laboratory, the CP set for verification should be

different from the one used for the local calibration of

ISI. Causes of failure of local ISI calibration need to be

sought out immediately and further advice from the

experts are required. Summary on the recommended

actions to take when failed to establish local ISI are

7

The procedures discussed above are outlined in a few

steps below:

1. Perform PT test on CP set (usually consist of four CPs

with different INRs).The routine procedure for PT

test should be followed which include checking the

internal quality control plasmas and instrument

standard operating procedure.

2. It is recommended to perform PT testing on CP in

duplicate over three sessions and determine the

mean INR from the three sessions on all CPs. Use the

ISI provided by the manufacturer PT reagent (as an

interim ISI) and the laboratory own MNPT for INR

calculation. If the mean INR for all CPs are within +/-

15% of the assigned INRs (provided by manufacturer)

the ISI and MNPT are valid to be used for calculation

of INR. The INR test has been verified and ISI

calibration is not required.

3. If the mean INR of the CP is not within +/- 15% of

assigned INR on all CPs, validate the MNPT and re-

establish a new MNPT and perform the step number

2 above following the new MNPT value.

4. If MNPT is valid, and the INR is still not within the

acceptable range (+/- 15% from the assigned INR as

in step 2), perform local ISI calibration by using CP set

and establish the local ISI value (different value from

the manufacturer assigned ISI). ISI can be determined

by using specific software. The calculation for ISI

using this software requires the PT of the CPs (in

seconds) measured locally by the laboratory PT

reagent and assigned INR values from the respective

CPs (provided by the manufacturer). Alternatively ISI

can be calculated using modified log-log graph,

usually provided by manufactures of CP.

5. Another INR verification step is needed if a new

locally established ISI value is obtained from the

calibration procedure above (step 4) by using

different lot of CP set or from different

manufacturer. Determine the mean INR again as in

step number 2 above. If the mean INR is within +/-

15% of the assigned INR on all CPs, implementation

of locally calibrated ISI value is then valid. Use the ISI

obtained from the local calibration procedure to

report INR.

6. If the mean INR is not within +/-15% of assigned INR

on all CPs tested, locally calibrated ISI is not valid to

be used to calculate INR. The next step is to refer to

further actions under failure of local ISI calibration

and get advice from the experts.

Steps to take in the event of failure to estimate

laboratory own local ISI:

1. Evaluate the instrument function

2. Test the system using different thromboplastin

3. Perform local PT/INR calibration using a different

set of certified plasmas

4. Contact the manufacturer of the CP used for

verification and calibration and follow their

recommendations.

It is important to emphasize again on continuous

monitoring of the test system by participation in EQA

programme and to repeat verification of INR regularly or

when required for example in the event of changing

reagents and etc.

References:

1. CLSI H47-A2: One stage PT test and APTT; Approved

Guideline

2. CLSI CLSI H54 A: Procedures for validation of PT/INR

systems: Approved guideline

3. Standardization of the INR: How good is your lab’s

INR and can it be improved: Emmanuel J Favaloro

and Dorothy M Adcock. Sem in throm and haemos

2008, vol 34; (7):593-603.

4. Time to think outside the box? Prothrombin time,

international normalised ratio, international

sensitivity index, mean normal PT and measurement

of uncertainty: a novel approach to standardisation.

EmmanuelJ Favaloro, Sayed Hamdam, Jane

McDonald, Wendy McVicker and Violeta

Ule.Pathology (April 2008) 40 (3): 277-287.

5. Guidelines on preparation, certification and use of

certified plasamas for ISI calibration and INR

determination. AMHP Van Den Besselaar et al. J of

Throm Haemost 2004, 2: 1949-1953.

Application 8

Dr Wan Zaidah Binti Abdullah, Haematologist at

Hospital Universiti Sains Malaysia (HUSM), Kubang

Kerian, Kelantan; Lecturer in Hematology at School

of Medical Sciences, Universiti Sains Malaysia

(USM), Kubang Kerian, Kelantan; Honorary Lecturer

at School of Health Sciences of USM, Kubang

Kerian, Kelantan & Advanced Medical and Dental

Institute of USM, Bertam, Pulau Pinang.

Email: [email protected]

Figure 1: Example of the template for ISI calibration by specific software

* Note: calculated ISI is obtained from the calibration using CP set (level A, B, C and D), refer to step 4 in the text

Venue : Date :

Instrument : Serial number :

PT Reagent Calibrated Plasma

Name : Lot number :

Exp. Date :

Laboratory MNPT (sec) 12.6Neoplastine ISI theoretical value (refer to package flyer) 1.24

INR (refer to package flyer) Result (sec)Level A 1.05 0.021189 13.5 1.130334Level B 2.1 0.322219 23.3 1.367356Level C 3.3 0.518514 33.4 1.523746Level D 6.9 0.838849 57.3 1.758155

Calculated ISI 1.30 % Difference -5%1.117855

Calculated MNPT 13.1 % Difference -4%

STA NEO CI PLUS101677Nov-09

AK-CalibrantOU63001Dec-09

ISI VERIFICATION

19-11-2008STA COMPACT A

MAKMAL HEMATOLOGI, HUSM

0.1

1

10

1 10 100

INR

sec

Application 9

Following the recent Hemostasis workshop that was

held at Hotel Shangri-La, we have gathered some of

the questions asked during the workshop and wished

to share with everyone. The questions were as

followed:

1. How frequent do we need to do the local system

verification for PT/INR test?

Local system verification should be done in all the

laboratories under similar conditions for the

establishment of the reference interval for the

PT. This verification should be performed if there

is :

a. change in reagents,

b. change in reagent lot number,

c. change of instrument

d. major instrument repair

e. major changes in quality control

f. major discrepancies in external

quality programs

g. no major changes occur, at least once

a year.

2. If more than one APTT reagents used in a

laboratory, how to describe the APTT sensitivity

to factors or APTT therapeutic range for

heparin?

For the determination of the sensitivity of APTT

reagents towards factor deficiency, a separate

determination test has to be done for separate

APTT reagents as we are testing the sensitivity of

a particular APTT reagent towards factor

deficiency and the sensitivity of each reagent has

to be described separately.

As for the APTT therapeutic range for heparin

therapy, the APTT therapeutic range for different

APTT reagents have to be done separately and

reported differently as well, it means that the

therapeutic range is reagent dependent.

Haemostasis Workshop:

Questions & Answers

Prof Madya Dr Leong Chooi Fun, Pusat Perubatan Universiti Kebangsaan Malaysia

3. Regarding APTT therapeutic range for UFH, since

it is difficult to get patients' sample with Heparin

concentrations ranging from very low to high, is

the spiked sample results acceptable for ISO15189

accreditation?

According to the College of American Pathologists

as well as Clinical and Laboratory Standards

Institute, determination of APTT therapeutic range

for heparin should be performed on blood samples

obtained from patients actually receiving heparin

(ex-vivo blood samples). Spiking of normal plasma

with heparin is not recommended because the in-

vitro spiked samples do not behave the same as ex-

vivo samples.

For the MS ISO 15189 accreditation, it does not

strictly prohibit the use of spiked samples for

determination of Heparin therapeutic range, we

need to prove that we are at the stage of collecting

real patients’ samples (Patients’ sample that are

processed within 2 hours of collection, double spun

and frozen can be used) to be used to run the

therapeutic range later.

4. How to interpret the sensitivity of APTT reagents

toward factor deficiency?

During the workshop, we have also identified that

the interpretation of sensitivity of APTT reagent

towards factor deficiency is rather confusing.

According to NCLI guidelines, an APTT reagent is

said to be sensitive for factor deficiency must

have the sensitivity within 30 to 45%.

Here, we would like to illustrate the sensitivity of 3

different APTT reagents towards Factor VIII using

the graphs plotted below. Assuming the APTT

reagents used were Reagent A, B and C. The APTT

results are plotted against the Factor VIII

concentration on the graphs below.

Application 10

10.0

100.0

1.0 10.0 100.0

AP

TT

(se

c)

FVIII (%)

Reagent A

Predetermined upper reference range for

APTT Reagent A : 36.4 sec

Sensitivity of reagent A to factor FVIII is

18%.

It means that Reagent A is able to show

prolonged APTT results only for samples

with factor levels below 18%. It is NOT

SENSITIVE enough for detection of factor

FVIII deficiency with factor VIII levels

above 18% but below 30% (mild

Hemophilia A)

In conclusion, this reagent is NOT

SENSITIVE and gives FALSE NEGATIVE

RESULTS for factor FVIII deficiency. Some

cases with mild FVIII deficiency may be

missed.

Reagent B

10.0

100.0

1.0 10.0 100.0

AP

TT

(se

c)

FVIII (%)

Predetermined upper reference range for

APTT Reagent B : 31.7 sec

Sensitivity of reagent B to factor FVIII is

38%.

It means that Reagent B is able to show

prolong APTT results for samples with

factor levels below 38%. It is sensitive

enough for detection of factor FVIII

deficiency with factor VIII levels upto 38%.

In conclusion, this reagent is SENSITIVE

and good for factor FVIII deficiency

detection. It can detect cases suspicious of

mild factor deficiency of FVIII levels up to

38%.

Application 11

36.4

38.0%

31.7

18.0%

Reagent C

10

100

1 10 100

AP

TT

(se

c)

FVIII (%)

Predetermined upper reference range for APTT Reagent C : 37.5 sec

Sensitivity of reagent C to factor FVIII is 60.0%.

It means that Reagent C showing prolonged APTT results for samples with factor levels up to

60%. It is OVER-SENSITIVE for detection of factor FVIII deficiency. It means that the patient’s

sample with normal factor VIII levels from 50-60% will be detected as APTT prolonged and subject

patients for unnecessary investigations of factor VIII deficiency.

In conclusion, this reagent is OVER-SENSITIVE for factor FVIII deficiency detection and giving

FALSE POSITIVE RESULTS.

Application 12

60.0%

37.5

Prof Madya Dr Leong Chooi Fun, Associated Professor in Department of

Pathology, Faculty of Medicine, National Universiti of Malaysia; Head of

Blood Bank Unit, Specialised Haemostasis Unit & Stem Cell Laboratory and

Consultant Haematologist, Pusat Perubatan Universiti Kebangsaan

Malaysia.


Application

Some frequently asked questions on the handling of Stago STA line analyzers.

Q1 What are the benefit of Neoplastine CI Plus?

- Neoplastine CI Plus reagent contains a specific heparin inhibitor. Therefore, the

prolongation of the PT time is related to a real deficiency of the prothrombin complex.

This reagent is insensitive to unfractionated heparin levels up to 1 IU/ml and to low

molecular weight heparin levels up to 1.5 anti

Q2 If you find that the reporting

programme, you can investigate the following:

- Did you establish MNPT for your current lot of Neoplastine CI Plus? The MNPT is key in

as ‘Reference Time’ on the STA Compact / STart in calibration menu for validation

purpose.

- However, if you are using different analyzer (such as STart or etc.) you need

the ISI value manually. The ISI value is auto

Q3 What can I do when the control value is outside the stated range?

- Check the assay conditions, operators’ procedure, reagents, integrity of the QC plasmas

(in term of preparation & stability).

Q4 What is the report unit for D.Dimer on STA

- D.Dimer level is expressed as initial fibrinogen equivalent units (FEU). FEU is the quantity

of fibrinogen initially present that leads to the observed level of D.Dimer.

quantity of D.Dimer is approximately half of an FEU. For example, a value of 0.50µg/ml

FEU is approximately 0.25 µg/ml D.Dimer unit.

Some frequently asked questions on the handling of Stago STA line analyzers.

What are the benefit of Neoplastine CI Plus?

Neoplastine CI Plus reagent contains a specific heparin inhibitor. Therefore, the



molecular weight heparin levels up to 1.5 anti-Xa IU/ml.

that the reporting of PT INR is high in the patient result or

programme, you can investigate the following:-

Did you establish MNPT for your current lot of Neoplastine CI Plus? The MNPT is key in


However, if you are using different analyzer (such as STart or etc.) you need

the ISI value manually. The ISI value is auto-update on STA-Compact.

What can I do when the control value is outside the stated range?

Check the assay conditions, operators’ procedure, reagents, integrity of the QC plasmas

reparation & stability).

What is the report unit for D.Dimer on STA-Compact?

D.Dimer level is expressed as initial fibrinogen equivalent units (FEU). FEU is the quantity

of fibrinogen initially present that leads to the observed level of D.Dimer.


FEU is approximately 0.25 µg/ml D.Dimer unit.

13

Neoplastine CI Plus reagent contains a specific heparin inhibitor. Therefore, the



PT INR is high in the patient result or in your EQC

Did you establish MNPT for your current lot of Neoplastine CI Plus? The MNPT is key in


However, if you are using different analyzer (such as STart or etc.) you need to change

Check the assay conditions, operators’ procedure, reagents, integrity of the QC plasmas

D.Dimer level is expressed as initial fibrinogen equivalent units (FEU). FEU is the quantity

of fibrinogen initially present that leads to the observed level of D.Dimer. The actual


Stago ApplicationStago ApplicationStago ApplicationStago Application SupportSupportSupportSupport

Stago International Application Manager – Mr Hubert Delabaere-

visited Malaysia on 8 – 11 September 2009. The purpose of Stago

Application visit is to update and monitor All Eights Stago application

team activities in Malaysia. We also made a few customer field visits in

Klang Valley (Hospital Kuala Lumpur, Pusat Perubatan Universiti

Kabangsaan Malaysia and Hospital Ampang) and out-station (Hospital

Universiti Sains Malaysia, Kubang Kerian, Kelantan and Hospital Raja

Perempuan Zainab II). We would like to extend our sincere

appreciation to our value customers in making the meetings with Stago

Representative a success.

"After visiting various laboratories in Malaysia, I was impressed by the

commitment and dedicated involvement by these laboratories in

achieving excellence in accreditation. This has caused a change in our

perspective that the quality in Malaysia is comparable with France and

other western countries. For a company like Diagnostica Stago, where

we are very actively involved in the accreditation process, we are

proud that Malaysia has achieved a new level in international

accreditation and believe that our teaching programs and the high

level of support from All Eights towards their customers played a

pivotal role towards this. Thank you to All Eights Malaysia for making

the Stago dream a reality.” – by Hubert Delabaere, International

Application Manager, STAGO.

Application 14

STA Compact STA Compact STA Compact STA Compact

Family Member…Family Member…Family Member…Family Member… Up to date, we have completed 14

user refreshing training for our

users throughout Malaysia and 4

new user training. On the other

hand, we are glad to have few

new installations in September -

Hospital Likas, Hospital Miri and

Hospital Tumpat. Warmest

welcome to new members in

joining our Stago family and let’s

give a big hug to them. We are

always promise ‘quality products

with a commitment for customer

service.’

Exclusively for STA-Compact users

Don’t miss the Don’t miss the Don’t miss the Don’t miss the

chance…chance…chance…chance… STA-QCE 200-3 & 4 is available in

October. To those who wish to

join this cycle, please do not miss

this chance. Please contact:

Ms Yunnie Tan (012-3735391)

When Expertise enhances When Expertise enhances When Expertise enhances When Expertise enhances

Information Update

When Expertise enhances When Expertise enhances When Expertise enhances When Expertise enhances PerformancePerformancePerformancePerformance

High throughp

sample capacity

Exclusive Viscosity

System

Easy to use

Windows® XP software

Complete Traceability

to support compliance with Good

Laboratory Practice and

Accreditation

The most flexible solution to

interface Haem

automated robotic lines

Total management of reagents with

70 positions on board reagent

put with 215 on-board

sample capacity

Viscosity-Based Detection

and versatile new

software

Traceability management

to support compliance with Good

Laboratory Practice and

he most flexible solution to

Haemostasis with

automated robotic lines

16

Total management of reagents with

70 positions on board reagent

DATE : 19

TIME : 2pm

VENUE : Sherat

(High

In conjunction with our launch, we have organized this puzzle and attractive prize to be won.

Step 1: Answer the following questions:

1. How many pathway are there in Haemostasis?

2. What is the last digit for on

3. Thrombin is also known as Factor _?

Please remember the answer in the sequence of the

Step 2: Attend the launching seminar.

Step 3: Use the number sequence acquired from the questions to solve the puzzle at the

launching seminar.

See you there!See you there!See you there!See you there!

Information Update

The unveiling of next step in Haemostasis & Hematology

Pentra

As Malaysia moves forward into the next step in Haemostasis and Hematology,

is proud to present the highest end of the STAGO and HORIBA family

Evolution Expert Series and the ABX Pentra DX 120 SPS Evolution.

19th

November 2009 (Thursday)

2pm – 6pm

Sheraton Imperial Hotel, Kuala Lumpur

(High-Tea is served)


: Answer the following questions:

are there in Haemostasis?

What is the last digit for on-board sample number on STA-R Evolution Expert Series

also known as Factor _?

Please remember the answer in the sequence of the questions asked.

: Attend the launching seminar.

: Use the number sequence acquired from the questions to solve the puzzle at the

See you there!See you there!See you there!See you there!


Pentra 120 SPS Evolution

Evolution Expert Series

As Malaysia moves forward into the next step in Haemostasis and Hematology,

proud to present the highest end of the STAGO and HORIBA family

Evolution Expert Series and the ABX Pentra DX 120 SPS Evolution.


R Evolution Expert Series?

: Use the number sequence acquired from the questions to solve the puzzle at the

17


SPS Evolution

Expert Series

As Malaysia moves forward into the next step in Haemostasis and Hematology, All Eights

proud to present the highest end of the STAGO and HORIBA family – the STA-R

LAUNCHING OF

STA-R EVOLUTION

AND

PENTRA DX120 + SPS EVOLUTION

LAUNCHING OF STA-R EVOLUTION AND PENTRA DX120 + SPS EVOLUTION

Time: 2.00pm

Date: 19 November 2009

Venue: Sheraton Imperial Hotel, Kuala Lumpur

Prefix : Prof / Dr / Mr / Mrs / Ms

Full Name : ____________________________________________________________________________________

Designation : ____________________________________

Organization : ____________________________________________________________________________________

Address : ____________________________________________________________________________________

____________________________________________________________________________________

Tel (Office) : ________________________

E-mail : _____________________________________________________

Please select:

Yes, I will be attending the event.

No, I will not be attending the event.

(Register before 19 October 2009)

�

Information Update

R EVOLUTION

SPS EVOLUTION

Participation

R EVOLUTION AND PENTRA DX120 + SPS EVOLUTION

2.00pm – 6.00pm (High-Tea is served)

19 November 2009

Sheraton Imperial Hotel, Kuala Lumpur

Prof / Dr / Mr / Mrs / Ms

____________________________________________________________________________________

____________________________________ Department: _________________________________

____________________________________________________________________________________

____________________________________________________________________________________

____________________________________________________________________________________

________________________ Tel (HP) : ______________________ Fax

____________________________________________________________________________________

No, I will not be attending the event.

Please return this form to:

ALL EIGHTS (M) SDN BHD

Tel: 03

Fax: 03

Contact person: Ms Poh Hui Yong


R EVOLUTION AND PENTRA DX120 + SPS EVOLUTION

____________________________________________________________________________________

_________________________________

____________________________________________________________________________________

____________________________________________________________________________________

____________________________________________________________________________________

Fax: ______________________

_______________________________


Tel: 03-5633 4988 Fax: 03-5633 0261

Contact person: Ms Poh Hui Yong


18

Unfractioned Heparin

anticoagulants widely used for the prevention and the treatment of venous

thromboembolism disease. Characterized by different pharmacological features

and clinical indications, UFH or LMWH may require labor

clinical cases.

To measure the

reagents, calibrators

THE METHOD OF CHOICE: anti

Enables the patient to reach the therapeutic range quicker.

Adjusting UFH using the anti-Xa assay results in fewer monitoring tests and dosage changes.

Specific test, insensitive to certain variables (preanalytical, a

TO COMPLY WITH THE INTERNATIONAL RECOMMENDATIONS: dedicated calibrators

For UFH calibration curve: → STA®

For LMWH calibration curve: → STA®

TO FURTHER THE EVOLUTION OF

Unique and single hybrid curve calibration UFH

heparin: → STA®-Hybrid Hep Calibrator (Cat.# 00687)

TO MONITOR FONDAPARINUX: specific calibrators and controls

Most suitable solution: →STA®

→STA®

A COMPREHENSIVE RANGE FOR

MONITORING HEPARIN THERAPY

A DEDICATED SOLUTION FOR YOUR

LABORATORY REQUIREMENTS

Information Update

Unfractioned Heparin (UFH) and Low Molecular Weight Heparin (LMWH) are



and clinical indications, UFH or LMWH may require laboratory monitoring in certain

clinical cases.

To measure the anti-Xa activity, Stago provides a comprehensive range of

calibrators and quality controls to meet your needs.

THE METHOD OF CHOICE: anti-Xa assay

Enables the patient to reach the therapeutic range quicker.

Xa assay results in fewer monitoring tests and dosage changes.

Specific test, insensitive to certain variables (preanalytical, analytical or physiological).


→ STA®-Hepanorm®H (Cat.# 00684)

→ STA®-Calibrator LMWH (Cat.# 00685)

TO FURTHER THE EVOLUTION OF THE LABORATORY PRACTICE: the hybrid curve

Unique and single hybrid curve calibration UFH-LMWH to monitor anti-Xa activity of both types of

Hybrid Hep Calibrator (Cat.# 00687)

TO MONITOR FONDAPARINUX: specific calibrators and controls

→STA®-Fondaparinux Calibrator (Cat. # 22354)

→STA®-Fondaparinux Control (Cat. # 00355)





(UFH) and Low Molecular Weight Heparin (LMWH) are



atory monitoring in certain

, Stago provides a comprehensive range of

to meet your needs.

Xa assay results in fewer monitoring tests and dosage changes.

nalytical or physiological).


THE LABORATORY PRACTICE: the hybrid curve

Xa activity of both types of





19

Are you interested to

contribute in this newsletter

publication?

If you have any technical or clinical experience in this

field that you wish to share with everybody, please do

not hesitate to contact us directly. As a token for your

contribution, we would like to award the contributor

with RM100 gift voucher on publication.

Any comment or input, please send to:

Marketing Department


45, Jalan TS 6/10A, Subang Industrial Park,

47610 Subang Jaya, Selangor Darul Ehsan,

Malaysia.

Tel: 603-5633 4988

Fax: 603-5633 0261


Website: www.alleights.com.my

ALL EIGHTS (M)

45, Jalan TS 6/10A, Subang Industrial Park, 47610 Subang Jaya,

Tel: (603) 5633 4988


6, Harper Road, #03

Tel: (65) 6288 6388 Fax: (65) 6284 9805




Selangor Darul Ehsan, Malaysia.

Tel: (603) 5633 4988 Fax: (603) 5633 0261

[email protected] Website: www.alleights.com.my

ALL EIGHTS (S) PTE LTD

6, Harper Road, #03-02 & #06-07 Leong Huat Building,

Singapore 369674

Tel: (65) 6288 6388 Fax: (65) 6284 9805

Email: [email protected] Website: www.alleight.com


ts.com.my

07 Leong Huat Building,

Website: www.alleight.com

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