Determination of thrombotic risk in patients with antiphospholipid syndrome using a modified thrombin generation assay

Introduction: Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL) that nonspecifically affect hemostasis. Although they prolong phospholipid-dependent coagulation in the laboratory, they are thrombogenic in vivo. One possible theory to explain this paradox is the inhibitory effect of antibodies on the hemostasis inhibition system. When, in particular, the activation protein C (APC) system requires phospholipid surfaces, its elimination may lead to an increase in thrombogenic potential and eventually to the clinical manifestation of thromboembolism [1] [2] [3] [4].

Objectives:

1. To determine thrombogenicity in a cohort of 175 patients with APS and concurrent positivity of various aPLs.

2. To determine thrombogenicity in 85 lupus anticoagulant (LA) positive patients with/without clinical manifestations of APS.

Method: We used the thrombin generation assay (TGA) modified by the addition of APC. TGA was measured with and without the addition of+APC and then we evaluated the ratio of the two measurements using a cut-off R≤4.5 (90th percentile) ([Fig. 1], [Fig. 2]).

Fig. 1  TGA: Patient at HIGH risk of thrombosis

Results: 1. We ranked the detected thrombogenicity from highest to lowest: triple positivity (LA, aCL, anti-β2GPI); single positivity (LA/ aCL/ anti-β2GPI/ anti-annexin V/ anti-PS/PT); anti-DI with simultaneous positivity of one or more other aPL (ANOVA p<0.05,<0.01,<0.001). 2. The group of patients (58) with clinical manifestations of APS showed higher thrombogenicity in 56.9% of patients, whereas the group of patients (27) who had not yet shown clinical manifestations of APS showed higher thrombogenicity in 25.9% of patients (Fisher&apos;s test p=0.0016).

Conclusion: Our findings seem to be particularly important for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.

Fig. 2  TGA: Patient at LOW risk of thrombosis

Supported by a grant from the Krajska zdravotni, a.s., KZ-2023-1-7

Publication History

Article published online:
13 February 2025

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