Dataset Information

Lupus anticoagulant test persistence over time and its associations with future thrombotic events.

ABSTRACT: Data on lupus anticoagulant (LA) test stability in patients persistently positive for LA are limited, and its implications on clinical outcomes are lacking. We investigated the rate and predictors of a negative LA test and whether experiencing a negative test affected a patient's risk of future thrombotic events or death in a prospective observational study of persistently LA+ patients. We followed 164 patients (84% women) for a median of 9.2 years and a total of 1438 follow-up visits. During the observation period, 50 thrombotic events (23 arterial and 27 venous events) occurred, and 24 patients died. Forty-six of the patients had at least 1 negative LA test during the observation period, corresponding to a 10-year cumulative incidence of a negative LA test of 28% (95% confidence interval, 20-35). The majority of patients with available follow-up after a negative LA test (n = 41) had at least 1 subsequent positive test for LA (n = 28/41, 68%). Vitamin K antagonist (VKA) treatment at baseline was associated with a negative LA test during follow-up. Using a multistate time-to-event model with multivariable adjustment, a negative LA test had no impact on a patient's prospective risk of thrombosis or mortality. We conclude that a negative LA test during observation cannot be used clinically to stratify a patient's risk for future events.

SUBMITTER: Colling ME

PROVIDER: S-EPMC9131910 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Lupus anticoagulant test persistence over time and its associations with future thrombotic events.

Colling Meaghan E ME Ay Cihan C Kraemmer Daniel D Koder Silvia S Quehenberger Peter P Pabinger Ingrid I Posch Florian F Gebhart Johanna J

Blood advances 20220501 10

Data on lupus anticoagulant (LA) test stability in patients persistently positive for LA are limited, and its implications on clinical outcomes are lacking. We investigated the rate and predictors of a negative LA test and whether experiencing a negative test affected a patient's risk of future thrombotic events or death in a prospective observational study of persistently LA+ patients. We followed 164 patients (84% women) for a median of 9.2 years and a total of 1438 follow-up visits. During th ...[more]

PMID: 35042230

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Project description:INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE. METHODS: Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n?=?31) or without (n?=?38) previous VD and from matched healthy controls (n?=?68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters. RESULTS: Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT. CONCLUSIONS: Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.

Dataset Information

Lupus anticoagulant test persistence over time and its associations with future thrombotic events.

Publications

Lupus anticoagulant test persistence over time and its associations with future thrombotic events.

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