Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 20;1(1):62-68.
doi: 10.1002/rth2.12006. eCollection 2017 Jul.

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

Gary W Moore  1 , James C Maloney  1 , Naomi de Jager  1 , Clare L Dunsmore  1 , Dervilla K Gorman  1 , Richard F Polgrean  1 , Maria L Bertolaccini  2
Affiliations

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

Gary W Moore et al. Res Pract Thromb Haemost. .

Abstract

Background: Gold 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.

Objectives: To investigate discrepancies from applying different algorithms to a common data set.

Methods: Diagnostic 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.

Results: Initial 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.

Conclusions: The 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.

Keywords: activated partial thromboplastin time; antiphospholipid syndrome; diagnostic algorithms; dilute Russell's viper venom time; lupus anticoagulant.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Lupus anticoagulant diagnostic algorithms. Numbers of the 311 samples classified as LA‐positive or –negative by dRVVT and/or dAPTT are shown for the junctures of each algorithm.
See this image and copyright information in PMC

References

    1. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295–306. - PubMed
    1. Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost 2014;40:163–71. - PubMed
    1. Pengo V, Tripodi A, Reber G, et al. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2009;7:1737–40. - PubMed
    1. Keeling D, Mackie I, Moore GW, Greer IA, Greaves M; British Committee for Standards in Haematology . Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012;157:47–58. - PubMed
    1. CLSI . Laboratory testing for the lupus anticoagulant; approved guideline. CLSI document H60‐A. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.

LinkOut - more resources