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Title: Laboratory detection of the antiphospholipid syndrome via calibrated automated thrombography
Authors: Devreese, Katrien ×
Peerlinck, Kathelijne
Arnout, Jozef
Hoylaerts, Marc # ×
Issue Date: Jan-2009
Publisher: F.K. Schattauer
Series Title: Thrombosis and Haemostasis vol:101 issue:1 pages:185-196
Abstract: Lupus anticoagulants (LAC) consist of antiphospholipid antibodies, detected via their anticoagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the antiphospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n = 30) and LAC patient plasma (n = 48 non-anticoagulated, n = 12 on oral anticoagulants), diluted 1:1 with a normal plasma pool. The anti-beta2-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 microg/ml). At variance, LAC patient 1:1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio, and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time, diluted Russell's viper venom time and silica clotting time, measured in 1:1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 microg/ml), spiked in the 1:1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence, the normalized thrombin generation-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants.
URI: 
ISSN: 0340-6245
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Biomedical Sciences Group Management - miscellaneous
× corresponding author
# (joint) last author

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