Variability of cut‐off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study

Tripodi, Armando; Chantarangkul, Veena; Cini, Michela; Devreese, Katrien; Dlott, Jeffrey S.; Giacomello, Roberta; Gray, Elaine; Legnani, Cristina; Martinuzzo, Marta; Pradella, Paola; Siegemund, A.; Subramanian, Sitalakshmi; Suchon, Pierre; Testa, Sophie

doi:10.1111/jth.13678

Cited by 31 publications

(42 citation statements)

References 18 publications

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“…Assay cutoffs from the literature or from manufacturers' instructions were applied to the interpretation of the results, rather than locally generated reference ranges as recommended for clinical use. 12 One reagent was tested for each assay; however, a number of different reagents are commercially available for DRVVT-and aPTT-based LA assays, and emicizumab could have differential effects on assay outcomes using these different systems. Additionally, further assays exist for the assessment of LAs than those evaluated in our study; the dilute prothrombin time in particular may warrant investigation, as our previous work found a very small reduction in standard prothrombin time in the presence of emicizumab.…”

Section: Current Guidelines For the Detection Of Las Recommendmentioning

confidence: 99%

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Adamkewicz¹,

Kiialainen

Paz‐Priel³

2019

Int J Lab Hematology

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Section: Current Guidelines For the Detection Of Las Recommendmentioning

confidence: 99%

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Adamkewicz¹,

Kiialainen

Paz‐Priel³

2019

Int J Lab Hematology

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“…9 Local cut-off and reference ranges are important, as there are differences depending on the reagent and analyzer used 21 as well as the method for calculating the values. 22 In our study, following venipuncture, blood samples were double centrifuged to obtain PPP and stored at −80°C, in accordance with national and international guidelines. [3][4][5] Notwithstanding the good agreement and precision in LA testing demonstrated between four Core Laboratories in the first part of our study, it is clearly important to monitor laboratory performance, particularly if laboratories are not experienced in performing haemostasis tests.…”

Section: Discussionmentioning

confidence: 99%

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository

Efthymiou

Mackie

Lane

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Variability remains a challenge in lupus anticoagulant (LA) testing. Objective To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. Methods Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non‐anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. Results Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non‐anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non‐anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. Conclusions Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.

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“…All had Gaussian distributions and were calculated as ±2 standard deviations (SD) of the mean . The ISTH recommendation of 99th percentile cut‐offs was not applied as it has proven controversial, and lower cut‐offs have been shown to allow better detection rates …”

Section: Methodsmentioning

confidence: 99%

“…2,4,5,22,23 The ISTH recommendation of 99th percentile cut-offs was not applied as it has proven controversial, and lower cut-offs have been shown to allow better detection rates. 2,4,5,24…”

Section: Essentialsmentioning

confidence: 99%

Application of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive discrepancies in some samples

Moore

Maloney

Jager

et al. 2017

Research and Practice in Thrombosis and Haemostasis

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BackgroundGold standard lupus anticoagulant (LA) assays and reference plasmas do not exist and detection is based on inference in a medley of coagulation assays, creating potential for interpretive discrepancies when applying different algorithms.ObjectivesTo investigate discrepancies from applying different algorithms to a common data set.MethodsDiagnostic data on 311 non‐anticoagulated patients LA‐positive by dilute Russell's viper venom time (dRVVT) and/or dilute activated partial thromboplastin time (dAPTT) assays were employed to compare algorithms. Routine testing applied interpretive criteria from guidelines endorsing classification as LA‐positive despite negative mixing tests, after exclusion of other clotting abnormalities. Integrated testing without mixing tests, and the classical algorithm where negative mixing tests preclude confirm tests, were then retrospectively applied to those data.ResultsInitial testing showed 92/311 (29.6%) were LA‐positive by dRVVT only, 156/311 (50.1%) by dAPTT only, and 63/311 (20.3%) by both assays. All dAPTT‐positive plasmas remained positive with integrated testing but eight dRVVT‐positives became negative. Other data suggested they were false‐negatives. The classical algorithm altered 52/155 (33.5%) dRVVT and 111/219 (50.7%) dAPTT interpretations to LA‐negative because of normal mixing tests, most of which were apparently weak LA in undiluted plasma.ConclusionsThe classical algorithm improves diagnostic specificity and confidence but risks missing some genuine LA due to false‐negative mixing tests. Integrated testing can be diagnostically accurate and logistically efficient but oversimplifies complex cases. Performing mix and confirm in response to an elevated screen with their interpretation based on clinical data, coagulation screens and the LA‐assay design offers a potentially valuable option.

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Variability of cut‐off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study

Abstract: Summary Background

Cited by 31 publications

References 18 publications

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Effects and interferences of emicizumab, a humanized bispecific antibody mimicking activated factor VIII cofactor function, on lupus anticoagulant assays

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository

Application of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive discrepancies in some samples

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