Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

Moore, Gary

doi:10.1186/1477-9560-5-12

Cited by 30 publications

(43 citation statements)

References 18 publications

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“…Although this is currently true for Textarin, preparations of Taipan and Ecarin venom for use in LA assays have been available for some years from at least one manufacturer. 38 The variation in epitope specificities, even for antibodies to domain I of β 2 glycoprotein I, 39 contributes to the fact that the dRVVT and aPTT combination alone cannot deliver diagnostic certainty. New or alternative assays are commonly evaluated against dRVVT and/or aPTT, and are thus disadvantaged because they may be sensitive to different antibody subpopulations.…”

Section: Which Screening Tests To Use and How Many To Use?mentioning

confidence: 99%

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Moore

2014

Semin Thromb Hemost

126

222

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Lupus anticoagulants (LA) are somewhat akin to subatomic particles and extrasolar planets, in that they are "detected" by inference, after exclusion of other possible causes of test findings. In the diagnostic setting, this makes LA detection both a challenge and a frustration, and guidelines from various expert groups have been published and updated over recent decades to outline current opinion on best practice. Problems such as antibody heterogeneity, reagent and analyzer variability, differing interpretation strategies, and absence of gold standards continue to conspire against generation of unequivocally ideal diagnostic strategies. Consequently, it is perhaps unsurprising that incomplete agreement exists between contemporaneous groups and their guidelines, even with some degree of author crossover. Indeed, it has been suggested that consensus guidelines on antiphospholipid antibody testing are particularly prone to The ISTH recommendation to employ only dRVVT and activated partial thromboplastin time is not mirrored in the BCSH and CLSI documents. The potential for false negatives in mixing tests is acknowledged by all panels, yet they remain mandated by ISTH as there are occasions when they are crucial to diagnostic accuracy. BCSH indicates that a negative mixing test need not exclude the presence of a LA, and CLSI reprioritizes test order to screen-confirm-mix, the latter being considered unnecessary in specific circumstances. Opinions in the guidelines differ on setting cutoff levels (i.e., 97.5th vs. 99th percentile for normally distributed data). All guidelines cover testing of anticoagulated patients, more detail being given by BCSH and CLSI, who suggest that Taipan snake venom time is a useful adjunct test in patients receiving vitamin K antagonists. Although complete agreement is not apparent, the guidelines represent significant moves toward engendering common practices.In Focus Article

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Section: Which Screening Tests To Use and How Many To Use?mentioning

confidence: 99%

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Moore

2014

Semin Thromb Hemost

126

222

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“…Recently, the reliability of mixing tests in LA detection has been questioned, with particular reference to the propensity for LA to be diluted to apparently undetectable levels . This can be a problem when, as indicated in ISTH 2009, the immediate response to an elevated screen is to perform the mixing test and use that as a decision point for whether to perform the confirm.…”

Section: Mixing Testsmentioning

confidence: 99%

“…Clinical and Laboratory Standards Institute 2014 takes this paradigm a step further and reprioritizes the order of testing to screen then confirm, and only performing the mixing test if initial testing is not clear cut. Otherwise, analytical limitations of mixing tests can lead to false‐negative reporting . Specific, concurrent criteria are given for when to omit the mixing test: Elevated LA‐screening test. Confirmatory test mathematically corrects screening test and returns into the RI, to exclude a coexistent abnormality. No evidence of other causes of elevated clotting times (i.e.…”

Section: Mixing Testsmentioning

confidence: 99%

“…It is important to consider that new or alternative assays tend to be evaluated against at least dRVVT, and commonly in conjunction with APTT. This creates a selection bias as other assays can be sensitive to subpopulations of clinically significant antibodies [7,[14][15][16][17][18]. Nonetheless, a well-performed dRVVT/APTT pairing has repeatedly been shown to be sensitive to most LA, and whilst there is a case for alternative assays in certain circumstances [2,3,7,[14][15][16][17][18], adoption of wider repertoires is probably unnecessary for all but reference laboratories or those with specific interest.…”

Section: Do Other Tests Have a Role In La Detection?mentioning

confidence: 99%

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Commonalities and contrasts in recent guidelines for lupus anticoagulant detection

Moore

2014

Int J Lab Hematology

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Summary Updates to guidelines covering lupus anticoagulant (LA) detection have recently been published by the International Society on Haemostasis and Thrombosis (ISTH) and British Committee for Standards in Haematology (BCSH), in 2009 and 2012, respectively. The Clinical and Laboratory Standards Institute (CLSI) published its first LA guideline in 2014. Cross‐panel agreement exists on sample manipulation, use of dRVVT analysis, conversion of clotting times to ratios, calculations to demonstrate phospholipid dependence, mixing test interpretation and provision of interpretive reporting. Whilst ISTH restricts assay choice to just dRVVT and activated partial thromboplastin time, BCSH and CLSI consider the case for additional tests. All panels acknowledge the potential for false‐negative mixing tests, yet they remain mandated by ISTH and BCSH, the latter, however, indicating that a negative mixing test need not exclude a LA if testing on undiluted plasma is unequivocal. CLSI reprioritizes test order to screen‐confirm‐mix to reduce false‐negative reporting when antibodies are diluted to undetectable levels in mixing tests. Recommendations differ on how to derive cut‐off levels, particularly in view of the realities of relatively low donor numbers. Each guideline considers testing of anticoagulated patients, BCSH and CLSI endorsing Taipan snake venom time as a useful supplementary assay in patients on vitamin K antagonists. Although full consensus is not apparent, these publications represent significant moves towards engendering common practices.

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“…On the other hand, tests based in viper venoms like Textarin, Ecarin and Taipan has been also excluded. However Textarin/Ecarin test would be an interesting tool when a patient on oral anticoagulants is evaluated, and Taipan viper venom time when a low levels of factor V is present, due to deficiency or inhibitor against this factor, because this venom is not dependent on factor V to activate prothrombin [38][39][40]. On the other hand Textarin needs PL and factor V to act.…”

Section: Comments On Different Aspects Of the Guidelinesmentioning

confidence: 99%

Laboratory Criteria of Antiphospholipid Syndrome Need to be Updated or Strictly Followed?~!2009-09-24~!2009-09-28~!2010-03-11~!

Martinuzzo¹

2010

TOAUTOJ

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The antiphospholipid syndrome is a very relevant disease that implicates different clinical features and laboratory criteria. Regarding laboratory diagnosis, it has been established in the last consensus that tests included are lupus anticoagulant (LA), anti cardiolipin (aCL) and anti 2 glycoprotein I antibodies (anti 2 GPI) of IgG or IgM isotype at medium to high titres. There is not one unique or a gold standard test for APS, so laboratory diagnosis is one of the more important problems. Considering LA testing, new guidelines have been recently published. They include not only the selection of coagulation tests, but also important recommendations about preanalytical variables, mixing and confirmatory studies interpretation, and cut off calculations. Taking into account solid phase assays, the major problem is the low reproducibility and the high inter assays variation. This problem has been recognized early with aCL. Despite many efforts such as the introduction of polyclonal and monoclonal standards, laboratory workshops, etc, the situation is still complicated. This problem was supposed to be solved when anti 2 GPI were introduced, but many collaborative studies and quality control surveys assessment have also demonstrated a lot of problems in standardization. The need of reference materials for LA and solid phase assays has been recognized many years ago but there is no clear advance in this line. Another important aspect is the fact that none of these tests are specific for APS, so they can be present in many clinical settings. Recent advances have been done by developing assays to detect anti domain I 2 GPI antibodies that could be more specific. It is hoped that in the near future, by worldwide collaborative actions, problems on laboratory diagnosis of APS will be overcome.

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Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

Cited by 30 publications

References 18 publications

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Commonalities and contrasts in recent guidelines for lupus anticoagulant detection

Laboratory Criteria of Antiphospholipid Syndrome Need to be Updated or Strictly Followed?~!2009-09-24~!2009-09-28~!2010-03-11~!

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