APS ACTION Investigators.
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ARTICLE SUMMARY FOR PATIENTS by the lead author, Dr. Elena Gkrouzman
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications in patients with “persistently positive” antiphospholipid antibodies (aPL). “Persistently positive” is defined as positive aPL at two occasions at least 12 weeks apart based on the APS classification criteria.
Diagnosis of APS is confirmed by the measurement of aPL in the blood using one of the following tests: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein-I antibodies (aβ2GPI). The assessment of aPL profile (the combination of positive aPL tests as well as the levels of these tests) during evaluation of aPL-positive patients is critical. Persistently positive aPL are more likely to have important clinical implications, while transiently positive aPL, especially of low level may be a result of infections or medications. Certain aPL profiles, such as LA positivity, high titer aCL/aβ2GPI, or triple-aPL positivity (LA, aCL, and aβ2GPI), are strongly associated with aPL-related clinical events, although traditional risk factors also need to be taken into account while evaluating aPL-positive patients.
The course of aPL positivity (whether persistently positive aPL tests continue to remain positive in the long term) is important in the risk stratification and management of APS patients; however, there are limited prospective data on the course of aPL tests over time. The goal of this APS ACTION study was to better understand this course, along with its clinical and laboratory associations. For this purpose, an international cohort of patients with persistently positive aPL tests with or without APS was utilized (APS ACTION Registry).
Using data from 472 patients, it was determined that approximately 80% of our international cohort with clinically meaningful aPL profile at baseline (defined as positive LA test and/or aCL/aβ2GPI IgG/M levels > 40 U) maintain such at an average follow-up of five years. Triple aPL-positivity at registry recruitment increased the chance of a stable, clinically meaningful aPL profile over time. Presence of another autoimmune disease such as lupus and use of medications such as hydroxychloroquine did not affect the chances of aPL profile stability. Moderate-to high levels (> 40 U) of aPL tests, positive LA, and two or more positive aPL tests at baseline were more likely to be associated with a stable, clinically meaningful aPL profile.
These results will guide future validation studies of aPL profiles in stored blood samples of patients in the APS ACTION Registry, bypassing issues of aPL test heterogeneity among different laboratories across the world, and interference of blood thinner use at time of LA testing. Stability of a clinically meaningful aPL profile over time may have further implications in the risk assessment for clinical events (blood clots or pregnancy complications), which will be studied in subsequent projects. Finally, this study may also inform frequency of aPL testing at follow up in clinical practice as certain aPL profiles are more likely to remain stable over time.
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PUBMED INFORMATION
Abstract
Objective: APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine a) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and b) predictors of unstable aPL profiles over time.
Methods: Clinically meaningful aPL profile was defined as positive lupus anticoagulant (LA) test and/or anticardiolipin (aCL)/anti-β2 glycoprotein-I (aβ2GPI) IgG/M ≥40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis.
Results: Of 472 patients with clinically meaningful aPL profile at baseline (median follow up: 5.1 years), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable; and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (p=0.906) and multivariable analysis (p=0.790). Baseline triple aPL positivity decreased (Odds Ratio [OR] 0.25, 95% Confidence Interval [CI] 0.10-0.64, p=0.004) and isolated LA test positivity increased (OR 3.3, 95% CI 1.53-7.13, p=0.002) the odds of an unstable aPL profile over time.
Conclusion: Approximately 80% of our international cohort patients with clinically meaningful aPL profile at baseline maintain such at a median follow-up of five years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.
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