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Volume 4 Issue 1 August 2013
Stago Newsle er
2
INSIDE THIS ISSUE:
STA Liatest D-Dimer Plus 2
STA Liquid Fib 3
STA Rivaroxaban Cals and QC 4
iHemOStasis 5
2013 Stago Catalogue 6
STA ImmunoDef VIII and IX 7-8
Dates to remember 9
Apixaban Cals and QC 9
STA Liatest® D-Dimer Plus D-Dimer is a routine test for most laboratories across the world. As a marker of fibrinolysis, it can be raised in various situations and play an important role in a diagnosis scheme, particularly when associated with other parameters and/or included in a clinical score (eg Wells score) determination. However, as of today, the main clinical uses of D-Dimer remain Deep Venous Thrombosis (DVT)/Pulmonary Embolism (PE) Exclusion and Disseminated Intravascular Coagulation (DIC) monitoring and diagnosis due to the prevalence and incidence of these diseases and well documented use of D-Dimer in these two diagnostic work-ups.
Criteria for selecting a good D-Dimer assay are influenced by international recommendations emanating from laboratory and clinical scientific societies, health authorities or state-of-the-art (eg. publications).
When selecting a D-Dimer assay, laboratories would therefore consider several aspects:
• Claimed and validated clinical performances for the main D-Dimer clinical indication (exclusion of DVT/PE)
• Analytical performances for reliable results
• Operational performances (practicability) for a use adapted to laboratories’ constraints and expectations.
STA Liatest® D-Di is widely used by laboratories across the world since its launch in 1998 and has been recognised for its excellent operational and analytical performances together with its well published and recognised clinical performances in VTE exclusion as well as in other indications.
Interferences with human antibodies present in patient samples are a commonly known issue that can be encountered when performing
immunoassays for diagnostic testing. The prevalence of such interfering agents is difficult to assess as it may vary considerably. Heterophilic antibodies, in particular Human Anti-Mouse Antibodies (HAMA) and Rheumatoid Factors (RF) are known to interfere with D-Dimer assays by over-elevating the result.
As this interference can lead to false positives and misdiagnosis – particularly in VTE exclusion – this issue has been reported in literature and customers have requested D-Dimer assay providers to identify and address this limitation when it exists.
As part of Stago’s continuous improvement commitment, The STA Liatest® D-Di PLUS has been designed as an evolution of the STA Liatest® D-Di specifically to address this need. With the addition of a blocking agent in the reaction buffer, STA Liatest® D-Di PLUS eliminates interferences associated with RF up to 1000 IU/ml and minimises interferences from heterophilic antibodies and HAMA, whilst keeping all other existing performances of STA Liatest® D-Di.
The same packaging, the same test setups, the same antibodies and latex, fully automated on Stago analysers, same 15 day on-board stability, same controls (00526 STA Liatest® Control N+P, and same rapid turn around time for results (< 7 minutes). In 2013, 00662 STA Liatest® D-Di PLUS will start to replace 00515 STA Liatest® D-Di. The identical and excellent performances of both assays will make for an easy transition for our customers.
If you would like to know more please contact us at [email protected]
3
may lead to bleeding and/or thrombosis . Traditionally, fibrinogen assays have been required in the investigation of haemorrhagic states .
The Clauss assay is considered as the reference method . A high concentration of thrombin is added to diluted test plasma and the clotting time is measured (Clauss, 1957). The test result is compared with a calibration curve prepared by clotting a series of dilutions of a reference plasma sample of known concentration, and a result in g/l is obtained.
Stago are pleased to announce a new reagent, the STA®-Liquid Fib , which is intended to replace both STA®-Fibrinogen 5 and STA®-Fib 2.
It features the following:
- a liquid format for an improved ease of use
- an extended stability to improve the
STA® Liquid Fib
Fibrinogen functions in primary haemostasis in support of platelet aggregation and in secondary haemostasis in the formation of an insoluble fibrin clot . It is the final clotting factor activated in the coagulation cascade.
Mainly synthesised in the liver , human fibrinogen is the product of three closely linked genes , each specifying the primary structure of the α, β and γ polypeptide chains, located on chromosome 4.
Inherited and acquired disorders can alter the quantity (afibrinogenemia and hypofibrinogenemia) and function (dysfibrinogenemia) of plasma fibrinogen.
Hypofibrinogenemia is generally asymptomatic , but afibrinogenemia and dysfibrinogenemia
laboratory efficacy
• The STA®-Liquid Fib is a high quality reagent that contributes to Stago's Premium Routine Line .
• Clauss method - Gold standard
• Working range 0.4 to 12 g/l - Covers all clinical situations, no need to re-test low QC with lower dilution (rare cases)
• Liquid format - Ready to use, no reconstitution steps
• Pre-calibrated, Time saving: no calibration required (Calibration is possible) and fully automated
• Barcoded reagents - Ensures traceability, Ease of use, confidence and security of results
• Extended stability - 10 days on board; 2 months at 2~8°C
• STAT compliance
- reagent available 24/7
- results available in a few minutes
• Optimized packaging/stability to enable no waste of reagent
Diagnostica Stago ANZ will be rolling this reagent out to our customers over the next 12 months.
If you would like to know more please contact us at [email protected]
00673 STA®-Liquid Fib
available soon
4
STA® Rivaroxaban QC and Calibrators
Rivaroxaban is a new oral
an�coagulant, direct factor Xa
Inhibitor, developed by Bayer
HealthCare and sold under the
trade name Xarelto®.
It is approved in three indica�ons in
Europe:
· preven�on of stroke and
systemic embolism in adult pa�ents
with non-valvular atrial fibrilla�on
(AF) with one or more risk factors
· treatment of deep vein
thrombosis (DVT) and preven�on of
recurrent DVT and pulmonary
embolism (PE) following an acute
DVT in adults
· preven�on of VTE in adult
pa�ents undergoing elec�ve hip or
knee replacement surgery.
In the US, Xarelto is approved for
stroke preven�on in AF pa�ents and
preven�on of VTE in hip or knee
surgery.
In April 2012, the TGA approved
Xarelto® for the preven�on of stroke
and systemic embolism in pa�ents
with non-valvular atrial fibrilla�on
(NVAF) and at least one addi�onal
risk factor for stroke, and treatment
of deep vein thrombosis (DVT) and
preven�on of recurrent DVT and
pulmonary embolism in Australia.
In total, Rivaroxaban is approved in
more than 110 countries worldwide.
This makes Rivaroxaban a future
major player in the world of
an�coagulants.
Rivaroxaban is contraindicated in
renal impairment (crea�nine
clearance <15mL/min), moderate
and severe hepa�c impairment with
elevated INR, or with azole
an�fungals or HIV-protease inhibi-
tors. These increase blood levels of
Rivaroxaban and therefore bleeding
risk.
The Stago STA®-Rivaroxaban
Calibrator & Control, is a new
solu�on for the determina�on of
Rivaroxaban concentra�on required
to support the examina�on of
pa�ents in different clinical
situa�ons.
This solu�on uses the an�-Xa
method (00311 STA®-Liquid
An�-Xa), is insensi�ve to analy�cal
and biological variables, and has a
wide working range.
00704 STA® Rivaroxaban Calibrator
(3 vials x 4 levels x 1ml)
00706 STA® Rivaroxaban Control
(3 vials x 2 levels x 1ml)
Email [email protected]
fax +61 3 9855 8999 or
phone 1800 4 78246 Australia
0508 4 78246 New Zealand
5
Stago are pleased to announce the release of our iPad application iHemOStasis . This application, available free of charge from the Apple App Store worldwide, is the first high-level educational tool exclusively dedicated to the in-depth study of Hemostasis and Thrombosis.
It includes:
5 animations related to Hemostasis:
♦ Primary Hemostasis,
♦ Coagulation Cascade,
♦ Fibrin Formation and Fibrinolysis,
♦ Inhibitors of coagulation,
♦ Anticoagulants
Special Focus
5 information "leaflets" on specific topics:
♦ Anticoagulants,
♦ Thrombin generation,
♦ Flow cytometry,
♦ Reference values: Hemostasis and Pediatrics
♦ Reference values: Hemostasis and Pregnancy
A Quick Guide to Hemostasis:
♦ Best practices,
♦ Reference values,
♦ Definitions and Glossary
Clinical Cases to test your knowledge with some real-life cases.
The iHemOStasis App is available now for download to iPad from the Apple App Store or iTunes (https://itunes.apple.com/app/id472966966) or scan the QR code above with your iPad.
iHemOStasis App
Scan this QR Code with your iPad
6
2013 Stago Catalogue The Stago 2013 Haemostasis Catalogue is available in softcopy or hardcopy.
Please drop us a line if you would like one and specify the desired format: [email protected]
7
STA® ImmunoDef VIII and IX
Factor VIII is a plasma protein produced in
the liver and by the re�culoendothelial
system. Factor VIII acts as a cofactor in
the factor Xa-genera�ng enzyme complex
of the intrinsic coagula�on pathway. In
plasma, the factor VIII circulates in a
complexed form with the von Willebrand
factor, F. VIII/VWF. In this complex, the
factor VIII is a ached to the von
Willebrand factor by a noncovalent
linkage. The factor VIII can be ac�vated by
thrombin and factor Xa; it increases the
ac�va�on of factor X by the factor IXa in
the presence of phospholipids and
calcium.
A normal plasma ac�vity in the adult
popula�on is usually between 60 and 150
% (0.6 - 1.5 IU/mL) (1). Reference values
may differ according to the pa�ent's age,
sex as well as within ethnic groups (2).
Ranges can be established in each
laboratory according to their pa�ent
demographics and results should be
interpreted as such. It is most important
to evaluate coagula�on results based on
the popula�on tested.
Haemophilia A (factor VIII deficiency) is
the most common recessively inherited
X-linked bleeding disorder. Almost
exclusively males are affected (1 in every
10 000 births). Es�ma�ons based on the
World Federa�on of Haemophilia's (WFH)
annual global surveys indicate that the
number of people with haemophilia in the
world is approximately 400 000. (h p://
www.wO.org/en)
It is characterized by mild, moderate or
severe bleeding episodes. The severity of
haemophilia is based on factor VIII:C level:
- < 1 % (< 0.01 IU/ml): severe
haemophilia,
- 1-5 % (0.01 - 0.05 IU/ml): moderate
haemophilia,
- 5-40 % (> 0.05 - < 0.40 IU/ml): mild
haemophilia.
Treatment consists of subs�tu�on with
plasma derived or recombinant Factor VIII
(rFVIII).
Factor VIII inhibitor is the most serious
complica�on of replacement therapy with
factor VIII in children with severe
haemophilia. In that case, the factor VIII
level is decreased. It remains unclear why
it concerns only propor�on of pa�ents
with haemophilia A. Several factors are
reported: gene�c, environmental,
immunologic, treatment type.
Inhibitors are a serious medical problem
that can occur when a person with
haemophilia has an immune response to
treatment with cloQng factor
concentrates. The immune system
defends the body from harmful bacteria
and viruses. Some�mes in the case of an
inhibitor, a person’s immune system
reacts to proteins in factor concentrates
as if they were harmful foreign substances
because the body has never seen them
before. When this happens, inhibitors
(also called an�bodies) form in the blood
to fight against the foreign factor
proteins. This stops the factor
concentrates from being able to correct
the bleeding problem.
Factor IX is a vitamin K-dependent serine
protease produced in the liver. It
circulates in the plasma in its inac�ve
form. Factor IX can be ac�vated in two
different ways:
– factor XIa, in the presence of Ca++,
ac�vates factor IX to factor IXa
– �ssue factor: factor VIIa complex
ac�vates either factor X or factor IX.
Factor IXa forms an enzyma�c complex
with phospholipids, Ca++ and factor VIIIa;
this complex then ac�vates factor X to
factor Xa. Factor IX has usually a normal
plasma ac�vity of 60 - 150% (0.6 - 1.5 IU/
mL).
Haemophilia B (factor IX deficiency) is the
second most common recessively
inherited X-linked bleeding disorder.
Almost exclusively males are affected (1 in
every 30 000 births).
The severity of haemophilia is based on
factor IX:C level:
- < 1 % (< 0.01 IU/ml): severe
haemophilia,
- 1-5 % (0.01 - 0.05 IU/ml): moderate
haemophilia,
- 5-40 % (> 0.05 - < 0.40 IU/ml): mild
haemophilia.
Treatment consists in subs�tu�on with
plasma derived or recombinant factor IX.
Factor IX inhibitor is the most serious
complica�on and in that case, the factor
IX level is decreased.
From a clinical point of view an accurate
diagnosis for Factor VIII / IX deficiency is
essen�al to determine the haemophilia
classifica�on and assess the clinical
severity. Accurate diagnosis of
haemophilia is necessary to allow
appropriate pa�ent management.
Treatment
Prophylac�c factor replacement therapy
is a prerequisite for pa�ent-tailored
treatment strategy. Prophylaxis is the
treatment by intravenous injec�on of
factor concentrate in order to prevent
an�cipated bleeding.
In their Quality Assurance of the
manufacturing process, manufacturers
check the compliance with specifica�ons
of the factors concentrates they
produce.
Tes�ng
a. FIRST LINE COAGULATION TESTING
An APTT prolonga�on occurs for factors
deficiencies in pa�ents but it is not
sufficient for haemophilia diagnosis.
APTT Mixing study could then be
performed:
APTT measurement of mix of pa�ent
plasma + Normal plasma. In the case of
mixing study correc�on, second line co-
agula�on tes�ng should be performed.
8
STA® ImmunoDef VIII and IX cont’d
b. SECOND LINE COAGULATION TESTING
A defini�ve diagnosis depends on the
factor assay to demonstrate a deficiency
of Factor VIII or IX.
- One stage assay is preferred by most
laboratories because of its simplicity and
automa�on. CloQng assay is the most
widespread. The Factor VIII / IX assay is
based on a comparison of the ability of
dilu�ons of standard and test plasmas to
correct the APTT of a plasma known to be
totally deficient in FVIII / IX but containing
all other factors required for normal
cloQng.
- For Factor VIII, two main alterna�ves to
the one stage assay exist: Two-stage APTT
based assay and two-stage chromogenic
based assay.
Both are based around an ini�al step to
produce factor Xa in a quan�ty
propor�onal to the amount of factor VIII
present and a second step to assay the
amount of factor Xa and so, deduce the
amount of factor VIII present.
In the chromogenic based assay, the
amount of FXa is measured by its ac�on
on a highly specific chromogenic sub-
strate. Since the colour intensity
produced is directly propor�onal to the
amount of FXa, which in turn is directly
propor�onal to the amount of FVIII, the
FVIII levels may be calculated from the
absorbance of the sample at a specific
wavelength (the op�mal absorbance
wavelength for the chromophore
produced by FXa cleavage of the
chromogen, e.g. 405nm for the commonly
used S-2765 chromogen).
Clinical plasma samples are assayed
mostly by one-stage assays, but
manufacturers of concentrates use the
chromogenic method, which is the
reference method of the European
Pharmacopoeia and the Interna�onal So-
ciety on Thrombosis and Haemostasis
(ISTH). But the chromogenic method is
not easily fully automated and can be very
expensive.
From the lab point of view, what are the
expecta�ons for factor assay
measurements?
► High standard performances
� To guarantee quality results &
pa�ent safety and especially at very low
levels for diagnosis and monitoring
treatment of pa�ents with haemophilia.
► Time effec�ve & easy to use product
for an op�mal cost management
� Customers would like to op�mise the
reagents used depending on their
laboratory ac�vity.
► Standardized results between labor-
atories for pa�ent follow up
� To have a consistent correla�on with
overall system.
► Compliance with Interna�onal
guidelines
The new STA-ImmunoDef VIII and IX
reagents have iden�cal principles to the
previous STA- Deficient VIII and IX
reagents.
The factor VIII and IX tests are
chronometric method based on one stage
cloQng �me method. Immuno-depleted
plasma, with all factors in excess except
factor VIII or IX, is added to pa�ent
plasma. The coagula�on is ac�vated by
the addi�on of the APTT reagent and cal-
cium.
Composi�on
► Packaging of STA – ImmunoDef VIII
(Cat. Nr. 00728) & IX (Cat. Nr. 00734)
� 6 vials x 1 mL
� Freeze-dried reagent
� Barcoded
� Dead volume: 0.5mL (use of
microcups or pooled vials is strongly
recommended to reduce the dead
volume)
� Theore�cal tests: 6x20 tests, ie 120
tests (iden�cal to STA – Deficient VIII &
IX).
► Shelf life: 24 months aXer
manufacturing
Key features
► Enhanced on board stability
The reagent is stable 8 hours on board.
Twice the stability of the current STA-
Deficient (4h).
► Extended Working range with one
unique calibra�on curve
STA® - ImmunoDef VIII: 0.7 to 400%
STA® - ImmunoDef IX: 0.7 to 300%.
There is no requirement for a low
calibra�on curve anymore.
► Stability of calibra�on
The frequency of the calibra�on is
reduced so it is no longer recommended
to perform calibra�on for each run. New
calibra�on is recommended only when
QC results are out of the range, typically
with change of lot number.
► Robustness of calibra�on curve
No addi�onal calibra�on and rerun of
QCs is necessary to obtain a valid
calibra�on.
► Addi�on of vWF factor in STA®-
ImmunoDef VIII. This follows the
Interna�onal guidelines for Besthesda &
Nijmegen test.
► A residual ac�vity < 1 %
If you would like to know more please contact us at [email protected]
00728 STA® ImmunoDef VIII
00734 STA® ImmunoDef IX
9
Dates to Remember
September 2 - 4, 2013
AIMS National Scientific Meeting 2013
Grand Hyatt Hotel Melbourne, Australia http://www.aims.org.au ____________________________________________________________
October 19 - 23, 2013
ASTH and HAA 2013 (ASTH Workshop October 19, 2013—Gold Coast Conferen ce & Exhibition Centre) Joint Annual Scientific Meeting of the HAA (HSANZ, ANZSBT and ASTH, 2013) Gold Coast Conference & Exhibition Centre Gold Coast, Australia http://www.fcconventions.com.au/HAA2013
____________________________________________________________
Diagnostica Stago Pty. Ltd.
651 Doncaster Road
Doncaster, VIC, 3108
Australia
Phone (AUS): 1800 4 STAGO
Phone (NZ): 0508 4 STAGO
Fax: +61 3 9855 8999
www.stago.com.au
AUSTRALIA - NEW ZEALAND
At the Heart of Haemostasis
New science and the transfer of knowledge leads to new standards of care, better patient outcomes and improved quality of life for the patients we serve.
Diagnostica Stago, has long been committed to providing educational support to haemostasis testing laboratories. Our customers participate by providing feedback and program requests on specific topics that may aid them in the use of our products or provide knowledge to better serve as their institution’s haemostasis resource.
Australian and New Zealand participants can achieve APACE and CPD continuing education credits and certificates by registering and completing the activities on this site.
Please visit:
http://www.stago-edvantage.com/
Educational Website
24 hours per day 7 days per week
Welcome to Stago-EdVantage.com
Stago APIXABAN Calibrators and Controls
Coming Soon in 2013
Congratulations to James Barker from Austin Hospital
winner of the Stago Prize at RMIT University-May 2013