Background/Purpose: Antiphospholipid antibody syndrome (APS) is a common cause for acquired thrombophilia. The group termed ‘seronegative’ APS has not made any headway in the revised APS ACR 2023 criteria as no new antibodies were included. Increased levels of Plasminogen activation inhibitor -1 (PAI-1) has been observed in patients with connective tissue disease. It may account for the increased risk of thrombotic events in APS the form of a second hit or function independently as a risk factor for thrombosis. We assessed the role of PAI-1 in antiphospholipid syndrome in relation to the presence of criteria antiphospholipid antibodies (aPL).

Methods: A case control study was done at a tertiary level Rheumatology centre in North India between September 2022 and 2024. The primary objective was to compare PAI-1 levels between those with APS (aPL+ APS), patients with thrombosis or obstetric morbidity but with antibody profile not satisfying criteria as put forward by the modified Sapporo criteria (aPL- APS) and healthy controls. An SLE group without APS or aPL was also included. Adults (age > 18 years) who had clinical features of APS as per the Modified Sapporo criteria were enrolled. Plasma levels of PAI-1 was estimated by sandwich ELISA. To obtain a power of 0.99 and a confidence interval of 0.95, a sample size of 24 was required in each group. Plasma tPA levels were also estimated in each group. Comparison between the 4 groups was done by ANOVA. Analysis was done using IBM SPSS statistics for windows [Version 26.0].

Results: Sixty-three cases of APS (females 84%) with mean age 35.2 (±8.9) were included. This included 38 aPL+APS and 25 aPL-APS cases (Table 1). Twenty-five SLE cases and 27 healthy controls were also included. Plasma PAI-1 levels were higher in aPL+APS compared to healthy controls (16.3 vs 10.6 ng/ml; p-0.03). The PAI-1 levels were similar among aPL-APS group, SLE controls and healthy controls. No specific aPL antibody (anticardiolipin, anti-β2GP1 or lupus anticoagulant) showed any association with PAI-1 levels. PAI 1 level was a positive predictor of thrombosis [OR 1.11 (1.01 – 1.22); p – 0.03]. This association remained significant after adjusting for age, gender, BMI, presence of SLE, presence of antiphospholipid antibodies and prednisolone intake (Table 2). There was no dichotomy in risk for arterial or venous thrombosis. Those with recurrences did not have higher PAI-1 levels [OR 1.07 (95% CI 0.98 – 1.17), p 0.09]. Higher PAI-1 levels reduced the risk of obstetric APS (n= 20) [OR 0.90 (0.82- 0.99). p =0.03]. Plasma tPA was higher in both antiphospholipid groups and SLE compared to healthy controls. It did not have any effect on thrombosis. There was a poor correlation between tPA and PAI-1 levels (r-0.11).

Conclusion: Plasminogen activation inhibitor 1 is an independent contributor of thrombosis in APS. Targeting PAI-1 directly or by drug repurposing may improve outcomes in APS.

Table 1. Clinical characteristics of the antibody positive and antibody negative antiphospholipid syndrome groups

Table 2. PAI-1 as a predictor of vascular and obstetric antiphospholipid syndrome

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasminogen-activator-inhibitor-1-increases-thrombotic-risk-in-antiphospholipid-syndrome/