Low extracellular vesicle–associated tissue factor activity in patients with persistent lupus anticoagulant and a history of thrombosis

Abstract

Lupus anticoagulants (LA) are a heterogeneous group of antiphospholipid antibodies (aPLAs) that promote thrombosis. Tissue factor (TF)–bearing extracellular vesicles (EVs) might contribute to the prothrombotic state of patients with persistent LA and a history of thrombosis. To investigate if EV-associated TF activity is elevated in a well-defined group of LA-positive patients with a history of thrombosis in comparison to that of healthy controls. Adult patients (n = 94, median age 40.1 years, interquartile range (IQR) 29.9–53.4; 87% females) positive for LA and a history of thrombosis (78% venous thrombosis, 17% arterial thrombosis, 5% venous thrombosis and arterial thrombosis) and healthy age- and sex-matched controls (n = 30, median age 42.9 years, IQR 38.6–45.8, 77% females) were included in this study. EV-TF activity was determined with a factor Xa generation assay and anti-β2-glycoprotein (anti-β2GPI) and anticardiolipin (aCL) antibodies by enzyme-linked immunoassays. EV-TF activity did not differ between 94 LA-positive patients with a history of thrombosis (median 0.05 pg/mL, IQR 0.00–0.14) and 30 healthy controls (median 0.06, IQR 0.00–0.11, p = 0.7745). No correlation was found between EV-TF activity and lupus-sensitive activated partial thromboplastin time (aPTT-LA) (rho = 0.034), Rosner index (rho = − 0.056), anti-β2GPI IgG (rho = 0.05), anti-β2GPI IgM (rho = − 0.08), aCL IgG (rho = 0.12), and aCL IgM (rho = − 0.11) in LA-positive patients. We found low EV-TF activity levels in LA-positive patients and a history of thrombosis and no correlation with analyzed aPLAs. Our data indicate that circulating TF-bearing EVs do not contribute to the prothrombotic state of patients with LA.

Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction

“…We measured functional extracellular vesicle-associated tissue factor (EV-TF) activity as previously described [22, 28]. We opted for measuring EV-TF instead of sole TF due to the higher reliability of the assay [24].…”

Extracellular Vesicles and Antiphospholipid Syndrome: State-of-the-Art and Future Challenges

“…Studies that examined platelet or monocyte EVs are inconsistent; while some studies found increased levels of platelet EVs in APS patients compared to HBDs [66,[68][69][70]72], others did not [67,71,73], and some reported increased levels of monocyte EVs [67,72], while others did not [68,71] (Table 1). In addition, it is known that aPL induce TF expression on endothelial cells and monocytes, but it is not clear whether this is accompanied by the release of TF + EVs [67,68,74] or not [69,71,75] (Table 1). The only study that investigated the presence of sEVs, that is, EVs of smaller size (<200 nm), in the plasma of APS patients found that their levels were significantly elevated compared to HBDs [76] (Table 1).…”

Implementation of a Risk-Stratified Anticoagulation Protocol Increases Success of Lower Extremity Free Tissue Transfer in the Setting of Thrombophilia

“…Lupus anticoagulant may be transiently present in the setting of certain medications (anticoagulants) or infections. 44,45 The relative infrequency of adverse events lowered our ability to identify independent predictors of flap outcomes in this study. In addition, the senior author's refined microsurgical expertise, despite technical consistency, may also partially account for improved flap success rates over time; however, the higher salvage rates and decreased postoperative thrombotic events support the benefit that implementation of a risk-stratified AC algorithm provides in thrombophilic patients undergoing LE free flap reconstruction.…”