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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-1-9
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-96
pubmed:meshHeading
pubmed-meshheading:19132207-Administration, Oral, pubmed-meshheading:19132207-Antibodies, Antiphospholipid, pubmed-meshheading:19132207-Antibodies, Monoclonal, pubmed-meshheading:19132207-Anticoagulants, pubmed-meshheading:19132207-Antiphospholipid Syndrome, pubmed-meshheading:19132207-Automation, pubmed-meshheading:19132207-Belgium, pubmed-meshheading:19132207-Blood Coagulation, pubmed-meshheading:19132207-Blood Coagulation Tests, pubmed-meshheading:19132207-Calibration, pubmed-meshheading:19132207-Case-Control Studies, pubmed-meshheading:19132207-Clinical Laboratory Techniques, pubmed-meshheading:19132207-Humans, pubmed-meshheading:19132207-Kinetics, pubmed-meshheading:19132207-Predictive Value of Tests, pubmed-meshheading:19132207-Protein C, pubmed-meshheading:19132207-Prothrombin Time, pubmed-meshheading:19132207-Sensitivity and Specificity, pubmed-meshheading:19132207-Thrombin, pubmed-meshheading:19132207-beta 2-Glycoprotein I
pubmed:year
2009
pubmed:articleTitle
Laboratory detection of the antiphospholipid syndrome via calibrated automated thrombography.
pubmed:affiliation
Coagulation Laboratroy, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.
pubmed:publicationType
Journal Article, Multicenter Study