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.
Email: [email protected]
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
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-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
as ‘Reference Time’ on the STA Compact / STart in calibration menu for validation
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.
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.
13
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
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
as ‘Reference Time’ on the STA Compact / STart in calibration menu for validation
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
quantity of D.Dimer is approximately half of an FEU. For example, a value of 0.50µg/ml
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)
In conjunction with our launch, we have organized this puzzle and attractive prize to be won.
: 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!
The unveiling of next step in Haemostasis & Hematology
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.
In conjunction with our launch, we have organized this puzzle and attractive prize to be won.
R Evolution Expert Series?
: Use the number sequence acquired from the questions to solve the puzzle at the
17
The unveiling of next step in Haemostasis & Hematology
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
Email: [email protected]
R EVOLUTION AND PENTRA DX120 + SPS EVOLUTION
____________________________________________________________________________________
_________________________________
____________________________________________________________________________________
____________________________________________________________________________________
____________________________________________________________________________________
Fax: ______________________
_______________________________
ALL EIGHTS (M) SDN BHD
Tel: 03-5633 4988 Fax: 03-5633 0261
Contact person: Ms Poh Hui Yong
Email: [email protected]
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
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 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).
TO COMPLY WITH THE INTERNATIONAL RECOMMENDATIONS: dedicated calibrators
→ 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)
A COMPREHENSIVE RANGE FOR
MONITORING HEPARIN THERAPY
A DEDICATED SOLUTION FOR YOUR
LABORATORY REQUIREMENTS
(UFH) and Low Molecular Weight Heparin (LMWH) are
anticoagulants widely used for the prevention and the treatment of venous
thromboembolism disease. Characterized by different pharmacological features
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).
TO COMPLY WITH THE INTERNATIONAL RECOMMENDATIONS: dedicated calibrators
THE LABORATORY PRACTICE: the hybrid curve
Xa activity of both types of
A COMPREHENSIVE RANGE FOR
MONITORING HEPARIN THERAPY
A DEDICATED SOLUTION FOR YOUR
LABORATORY REQUIREMENTS
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
ALL EIGHTS (M) SDN BHD
45, Jalan TS 6/10A, Subang Industrial Park,
47610 Subang Jaya, Selangor Darul Ehsan,
Malaysia.
Tel: 603-5633 4988
Fax: 603-5633 0261
Email: [email protected]
Website: www.alleights.com.my
ALL EIGHTS (M)
45, Jalan TS 6/10A, Subang Industrial Park, 47610 Subang Jaya,
Tel: (603) 5633 4988
Email: [email protected]
6, Harper Road, #03
Tel: (65) 6288 6388 Fax: (65) 6284 9805
Email: [email protected]
ALL EIGHTS (M) SDN BHD
45, Jalan TS 6/10A, Subang Industrial Park, 47610 Subang Jaya,
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
45, Jalan TS 6/10A, Subang Industrial Park, 47610 Subang Jaya,
ts.com.my
07 Leong Huat Building,
Website: www.alleight.com