Summary
Lupus anticoagulants (LAC) consist of antiphospholipid antibodies, detected via their
anticoagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid
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-β2-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 μg/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 μg/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.
Keywords
Thrombosis - α
2-glycoprotein I - lupus anticoagulants - prothrombin - antibodies