Can APC inhibition by lupus anticoagulants indicate antibody thrombogenicity?

Introduction Lupus anticoagulans is the most important factor in the detection of antiphospholipid syndrome (APS). APS is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL) that nonspecifically affect hemostasis. The effect is due to their binding to phospholipid surfaces, thereby prolonging screening coagulation tests such as aPTT, but this does not correlate with the incidence of thrombotic complications in APS. This situation is clarified by the theory that the main target of antibodies is the activated protein C (APC) system, the elimination of which may manifest as thrombotic complications.

Method The aim of this study was to determine the thrombogenicity of lupus anticoagulans antibodies using a modified thrombin generation assay inhibited by protein C (TGA) in a cohort of 90 samples with suspected APS. TGA was measured with/without APC and the ratio of the two measurements (as for APC resistance) was evaluated, with a cut-off of ≤4.5 (90th percentile) calculated using 21 patients with factor V Leiden heterozygous mutation (FV Leiden heterozygote).

Results The cohort was divided according to the prevalence of lupus anticoagulans into low, intermediate and high titers. The results of the modified TGA test showed that the incidence of patients with low TGA ratio did not depend on lupus anticoagulans antibody titer (low titers 35 %, intermediates titers 27 % and high 30 %), but at the same time it correlates very well with the clinical manifestation of APS in these patients ([Fig. 1]).

Fig. 1  Thrombogenicity lupus anticoagulans antibodies.

Conclusion Performing TGA may help us to identify patients in all groups who are at risk of thrombotic and pregnancy complications. For this reason, it appears beneficial to include thrombogenicity determination by the modified TGA test in all positive lupus anticoagulans antibody detections.

Supported by grant LF-2022-001 a MH CZ - DRO (FNOl, 00098892)

Publication History

Article published online:
20 February 2023