Abstract Number: PB1644
Meeting: ISTH 2020 Congress
Background: Many mechanisms are involved in thrombotic processes that contribute to morbidity in patients with systemic lupus erythematosus (SLE). Global coagulation tests may be valuable to evaluate SLE hypercoagulable state.
Aims: To characterize the prothrombotic state by Rotational Thromboelastometry (ROTEM®) and Calibrated Automated Thrombogram (CAT®) in SLE not mediated by antiphospholipid antibodies (aPL).
Methods: 32 patients with SLE without aFL and 88 healthy controls were recruited after signing the informed consent. Experimental protocol was approved by La Paz University Hospital Ethics Committee. Kinetic clot formation was determined by ROTEM®. Platelet activation markers, exposure of phosphatidylserine (PS) and caspase activities were determined by flow cytometry. To generate neutrophil extracellular traps (NETs) neutrophils from controls or SLE patients were stimulated with 100 nM PMA and cocultivated with PRP from healthy controls adjusted to 105 platelets/µL with/without corn trypsin inhibitor (CTI) to block contact phase. Thrombin generation associated to NETs and to microparticle’s (MPs) content of tissue factor (TF) was measured by CAT. Plasma levels of cfDNA and of PAI-1 were also determined. Statistical analysis was performed by Prism-Graphpad.
Results: ROTEM® showed a procoagulant profile in SLE patients (Fig 1 A). Plasma PAI-1 was increased in SLE patients (Fig.1B) and its levels correlated with several ROTEM parameters (Fig. 1C). SLE patients showed a basal platelet activation and a higher PS exposure (Fig.1D) that was not due to an enhanced apoptosis and an increased thrombin generation associated to TF content of MPs, to cfDNA and to NETs (Fig.2). cfDNA- and NETs- associated thrombin generation were prevented by CTI.
Conclusions: ROTEM® detected a hypercoagulable state in SLE patients that might be linked to increased plasma PAI-1, basal platelet activation with a consequent enhanced exposure of PS, augmented TF-containing MPs and cfDNA. Moreover, neutrophils from SLE patients seemed more prone to form NETs than those from healthy controls.
To cite this abstract in AMA style:Monzón Manzano E, Fernández Bello I, Robles Marhuenda Á, Justo Sanz R, Acuña Butta P, López Longo FJ, Álvarez Román MT, Jiménez Yuste V, Butta Coll N. Characterization of the Hypercoagulable State and NETosis in Systemic Lupus Erythematosus [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/characterization-of-the-hypercoagulable-state-and-netosis-in-systemic-lupus-erythematosus/. Accessed January 23, 2022.
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