Screening Assays for the Diagnosis of Lupus Anticoagulant (LA) - NewHemosILTM - Enhance LA Screening with
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New HemosIL TM
Screening Assays for the Diagnosis of Lupus
Anticoagulant (LA)
Hemostasis
Enhance LA Screening with a
Complete Panel of Fully
Automated Assays
Innovation. Leadership. Commitment.
Screening Assays for the Diagnosis of Lupus Anticoagulant (LA)
Antiphospholipid Syndrome (APS)
APS is an autoimmune disorder in which The in vitro effect of LA is based on the formation
antiphospholipid (aPL) antibodies are associated of complexes between the auto-antibodies and
with venous and arterial thrombosis, recurrent proteins. The formation of these complexes is
fetal loss, repeated unexplained spontaneous enhanced in the presence of phospholipids.
abortion or premature birth.
For this reason, LA testing is mainly based on the
The laboratory criteria used to support the prolongation of clotting times of different assays
diagnosis of APS are based on the presence such as diluted PT and APTT, dRVVT or KCT.
of LA, Anticardiolipin antibody (aCL) or
anti-β2-Glycoprotein-I antibody. These assays use very low phospholipid
concentrations, which makes them sensitive
LA is a class of auto-antibodies which may be to anti-phospholipid antibodies. Due to the
directed toward different human proteins: heterogeneity of plasma auto-antibodies and
β2-glycoprotein-I and Prothrombin primarily, the variable sensitivity of assays, the approach
but also Protein C, Protein S and Annexin V. to LA diagnosis is based on multiple tests.
LA Testing
Laboratory diagnosis of LA is a complex To demonstrate phospholipid dependence, the
procedure, based on the following criteria: most recent SSC-ISTH recommendations on LA
require the use of two different phospholipid-
• Prolongation of phospholipid-dependent assays dependent clotting assays, based on different
• Exclusion of Factor deficiencies methodologies.
• Phospholipid-dependence
• No effect from Factor inhibitors
General Screening
LA may be detected by performing general In addition, prolongation of clotting times
screening assays, such as PT and APTT. above the normal range may have many causes,
However, PT and APTT reagents are generally including the presence of Factor deficiencies,
not designed to be sensitive to all types of LA, Factor inhibitors or anticoagulants. Samples
and because of the variety and heterogeneity of demonstrating prolonged clotting time should
plasma anti-phospholipid antibodies, they cannot be thoroughly assessed before proceeding with
be used alone for the diagnosis of LA. LA investigation.
Normal
PT
Abnormal: Warfarin? Factor deficiencies?
Citrated Inhibitors to coagulation factors?
Plasma
Normal
APTT
Abnormal: Heparin? Factor deficiencies?
Inhibitors to coagulation factors?
Abnormal: Heparin
TT (most likely)
Normal
Silica Clotting Time
Screen (low phospholipid concentration) and Confirm
(high phospholpid concentration) in the same kit
Liquid formulation, easy to use, fully automated
Suitable for mixing studies and oral
anticoagulant-treated patient samples
Sensitive to LA
β2 -Glycoprotein-I antibodies
Sensitive to anti-β
LAC Screen and LAC Confirm
Based on dRVVT, is the most common Screening
and Confirmatory test for LA in the laboratory
Easy to use, fully automated
SCT and LAC Screen/Confirm
Cover the maximum spectrum of antiphospholipid
antibodies
Results for both are expressed as Normalized Ratio
In accordance with the most recent SSC-ISTH
recommendations on LA screening
The combination of SCT and LAC Screen and Confirm
are more informative and more likely to differentiate
LA from anti-FVIII inhibitors, than either test alone
The combination of SCT and LAC Screen and
Confirm had the highest sensitivity in the detection
of LA in patients who met the clinical criteria for APS
Screening Algorithm for LA with HemosIL Assays
The use of both SCT and LAC Screen and Confirm assays The charts below, demonstrate the major analytical steps in
enhances the identification of LA patient samples, due to the diagnosis of LA.
their different sensitivities to anti-phospholipid antibodies.
Silica Clotting Time (SCT) Screening and confirmatory APTT-based assays
performed using SCT Screen and SCT Confirm
reagents, containing low and high concentrations
of phospholipids respectively.
LAC Screen and Confirm Screening and confirmatory dRVVT-based assays
performed using LAC Screen and Confirm reagents,
containing low and high concentrations of
phospholipids respectively.
LA Investigation
Platelet- LA Screening
Free
Plasma SCT Screen and LAC Screen
LA Confirmatory LA Confirmatory
SCT Confirm LAC Confirm
NOTE:
- Exclude the effect due to the presence
of Factor deficiencies or Factor
* N.R < cut-off: SCT (-) * N.R > cut-off: SCT (+) * N.R < cut-off: LAC(-) * N.R > cut-off: LAC(+) inhibitors on the Normalized Ratios.
- Exclude the effect of Heparin
on the Normalized Ratios.
See package insert for details
on Heparin interference.
SCT and LA Results Analysis - Samples from oral anticoagulant-
treated patients may affect the
Normalized Ratios.
No LA SCT (-) and LAC (-)
SCT (+) and LAC (+)
SCT (+) and LAC (-) If none of the conditions above apply, LA
is highly probable.
SCT (-) and LAC (+)
*N.R.: Normalized Ratio. See package insert for instructions on calculating N.R.HemosIL Silica Clotting Time and LAC Screen and Confirm
Silica Clotting Time (SCT) LAC Screen and Confirm
Part number 0020004800 0020008000 and 0020008200
Stability 2-8 C 20 Days 48 Hours
Stability on-board 5 Days 3 Days
Results Screen Ratio Screen Ratio
Normalized SCT Ratio = Normalized LAC Ratio =
Confirm Ratio Confirm Ratio
Precision Mean CV% CV% Mean CV% CV%
(N. Ratio) Within run Total (N. Ratio) Within run Total
Normal ~1.5New HemosILTM
Screening Assays for the Diagnosis of Lupus Anticoagulant (LA)
Reagent Part Kit
Number Configuration
Silica Clotting Time (SCT) 0020004800 SCT Screen 3 x 5 mL
SCT Confirm 3 x 5 mL
SCT CaCl2 3 x 10 mL
LAC Screen 0020008000 10 x 2 mL
LAC Confirm 0020008200 10 x 2 mL
References Europe, America and Pacific Rin
1. Horbach DA, Van Oort E, Donders RCJM, Derksen RHWM, De Groot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients
with systemic lupus erythematosus – Comparison between different assays for the detection of antiphospholipid antibodies. Thromb Haemost 1996; 76:916 - 24.
2. Whal DG, Guillemin F, de Maistre E, Perret C, Lecompted T, Thibaut G. Risk of venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus.
Lupus 1997; 6: 467 - 73.
3. Galli M. Which antiphospholipid antibodies should be measured in the antiphospholipid syndrome? Haemostasis 2000; 30 (Suppl. 2) 57 - 62.
4. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement
on preliminary classification criteria for definite antiphospholipid syndrome: report of international workshop. Arthritis Rheum 1999; 42: 1309 - 11.
5. Brandt JT, Triplett DA, Alving B, Sharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995; 74: 1185 - 90.
6. Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost 2001; 86: 83 - 91.
7. Chantarangkul V, Tripodi A, Arbini A, Mannucci PM. Silica Clotting Time (SCT) as a screening and confirmatory test for detection of lupus anticoagulants. Thromb Res 1992; 67: 355 - 65.
8. Chantarangkul V, Tripodi A, Clerici M, Bressi C, Mannucci PM. Laboratory diagnosis of lupus anticoagulants. Thromb Haemost 2002; 87:854 - 8.
9. Dragoni F, Minotti C, Palumbo G, Faillace F, Redi R, Bongarzoni V, Avvisati G. As compared to kaolin clotting time, silica clotting time is a specific and sensitive method for
detecting lupus anticoagulant. Thromb Res 2001; 101: 45 - 51.
10. Galli M. Dlott J, Norbis F, Ruggeri L, Cler L, Triplett DA, Barbui T. Lupus anticoagulants and thrombosis: clinical association of different coagulation and immunological tests.
Thromb Haemost 2000; 84: 1012 - 6.
11. Montaruli B, Vaccarino A, Foli C, Rus C, Agnes C, Saitta M, Bazzan M. Lupus Anticoagulant: Performance of a New, Fully Automated Commercial Screening and Confirmation Assay.
Clin Chem 2005; 6: 1031-1033.
12. Tripodi A, Mancuso ME, Chantarangkul V, Clerici M, Bader R, Meroni PL, Santagustino E, Mannuci PM. Lupus Anticoagulants and their Relationship
with the Inhibitors against Coagulation FVIII: Considerations on the differentiation between the 2 Circulating Anticoagulants. Clin Chem 2005; 10: 1883-1885
13. Grypiotis P, Ruffati A, Pengo V, Tonello M, Biasiolo A, Zamboni D, Cavazzana A, Todesco S. Use of a New Silica Clotting Time for Diagnosing
Lupus Anticoagulant in Patients Who Meet the Clinical Criteria for Antiphospholipid Syndrome. Journal of Clinical Laboratory Analysis 2006; 20: 15-18
14. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).J Thromb Haemost. 2006 Feb;4(2):295-306.
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Applications/tests listed may not yet be approved by the regulatory authorities in every country.
IL product specifications are subject to modification to assure the highest quality performance.
Some of the IL sites may still be in the process of completing ISO.
HemosIL and ACL are trademarks of Instrumentation Laboratory. HemosIL reagents are not available in all countries
© Instrumentation Laboratory 2006
p/n 98091-24 EU Rev. 0
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