Guidelines on the investigation and management of antiphospholipid syndrome

Greaves, Michael; Cohen, Hannah; Machin, Samuel J.; Mackie, Ian

doi:10.1111/j.1365-2141.2012.09037.x

Cited by 505 publications

(679 citation statements)

References 117 publications

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“…This is a reflection of the well‐described phenomena of antibody heterogeneity and reagent variability,2, 6, 7, 8, 10, 11, 12, 26, 27, 28, 29 which at its most extreme, can result in a given dRVVT and APTT pairing detecting a particular antibody while another pairing would not. Screen and mix ratios and ICA values were similar between the two dRVVT reagents, possibly due, at least in part, to normalizing the data reducing between reagent differences 28, 29…”

Section: Discussionmentioning

confidence: 98%

“…Without exception, MTC showed higher sensitivity than ICA in detection of known LA with every reagent. Mixing tests are recommended in all current guidelines6, 7, 8 although different approaches are advocated. The guidelines of Lupus Anticoagulant/Phospholipid‐Dependent Antibodies Subcommittee of the Scientific and Standardisation Committee (SSC) of International Society on Thrombosis and Haemostasis (ISTH) advocates performing the mixing test immediately after recognizing an elevated screening test and the results of mixing test are suggestive of LA when their clotting times or ratios are above the local cut‐off value, or when ICA is greater than the local cut‐off value 6.…”

Section: Discussionmentioning

confidence: 99%

“…The guidelines of Lupus Anticoagulant/Phospholipid‐Dependent Antibodies Subcommittee of the Scientific and Standardisation Committee (SSC) of International Society on Thrombosis and Haemostasis (ISTH) advocates performing the mixing test immediately after recognizing an elevated screening test and the results of mixing test are suggestive of LA when their clotting times or ratios are above the local cut‐off value, or when ICA is greater than the local cut‐off value 6. The British Society for Haematology (BSH) guideline also suggests performance of the mixing test in response to finding an elevated screening test and goes on to indicate the limitation introduced by the dilution effect and how LA can, in certain circumstances, be detected despite a negative mixing test 7. On the other hand, the CLSI guideline supports initial performance of screening and confirmatory assays to evidence phospholipid dependence.…”

Section: Discussionmentioning

confidence: 99%

“…While aCL and aβ2GPI assays can be calibrated to generate quantitative results in semi‐arbitrary units to aid interpretation, a medley of phospholipid‐dependent coagulation assays are employed for LA detection and the presence of LA is inferred or excluded from the result patterns obtained. This additional complexity to LA detection further complicates diagnosis and some LA guidelines with broad but not complete agreement are available to lead best practices 6, 7, 8…”

Section: Introductionmentioning

confidence: 99%

“…There is no single test to detect all LA1, 6, 7, 8 and guidelines recommend performance of two different tests that represent different assay principles, the diluted Russell's viper venom time (dRVVT) and a LA‐sensitive activated partial thromboplastin time (APTT) 6, 7, 8. The assay medley for test types involves: (i) a screening test with low phospholipid concentration to find the effect of LA, (ii) mixing test in the screening test by a 1:1 mixture of index and normal pooled plasma (NPP) to show inhibition, and (iii) recapitulation of the screening test but with high phospholipid concentration to evidence phospholipid dependence as the confirm procedure 6, 7.…”

Section: Introductionmentioning

confidence: 99%

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Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test‐specific cut‐off than index of circulating anticoagulant

Kumano

Moore

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials Various approaches are available for interpreting lupus anticoagulant mixing tests.Mixing test specific cut‐off (MTC) was compared with index of circulating anticoagulant (ICA).MTC was superior to ICA in detecting inhibition by lupus anticoagulant (LA) in multiple reagents.Detection rates of LA can be improved by the method to interpret the results. BackgroundLupus anticoagulant (LA) is classified in the antibody family that is recognized as antiphospholipid antibodies. Guidelines for LA detection recommend mixing test interpretation with either a mixing test specific cut‐off (MTC) or index of circulating anticoagulant (ICA). We previously evidenced that MTC was superior to ICA in detecting the in vitro inhibition of LA with a single dilute APTT (activated partial thromboplastin time) and dRVVT (diluted Russell's viper venom time) pairing.ObjectivesThe objective in the present study was to compare the LA diagnostic effectiveness of MTC and ICA by multiple APTT and dRVVT reagents.MethodsOne hundred‐five samples from non‐anticoagulated patients positive for LA in the dilute APTT (dAPTT) and dRVVT reagent pairing employed for diagnostic examination were performed by undiluted and in a 1:1 mix with normal pooled plasma with four additional APTT reagents and another dRVVT reagent (dRVVT B).ResultsFrequencies of MTC and ICA positivity were determined from samples LA positive in undiluted plasma. MTC positivity in mixing test were 63%, 77%, 80%, 84%, 46%, 81%, and 72% in 4 APTT, dAPTT and 2 dRVVT, respectively. ICA positivity were 47%, 67%, 58%, 54%, 42%, 47%, and 29%, respectively. There were no samples of ICA‐positive/MTC‐negative with any reagent.ConclusionsThe data indicate that MTC is superior to ICA for LA detection in mixing tests in multiple reagents and reagent types. Although mixing tests may make weak LA samples appear negative, the efficacy of LA detection can be improved by the method to interpret the results.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test‐specific cut‐off than index of circulating anticoagulant

Kumano

Moore

2018

Research and Practice in Thrombosis and Haemostasis

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Bleeding and Recurrent Thrombosis in Definite Antiphospholipid Syndrome

Ruiz‐Irastorza¹,

Khamashta²,

Hunt³

et al. 2002

Arch Intern Med

162

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The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses.

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