CO074 | WHOLE-BLOOD COAGULATION AND PLATELET DYNAMICS IDENTIFY DIFFERENTIAL PROTHROMBOTIC STATES IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH JAK OR TNFⱭ INHIBITORS

L. Spiezia, A. Giollo, L. Di Luozzo, M. Salvato, K. Khalid, R. D’Andrea, A. Benetti, C. Samà, R. Ramonda, P. Simioni | Dipartimento di Medicina, Azienda Osp. Università di Padova, Italy

Background and Aims. Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized not only by joint involvement but also by systemic manifestations, including a prothrombotic state driven by persistent inflammation. This condition is associated with increased activation of the coagulation cascade, impaired fibrinolysis, and heightened platelet activation, ultimately contributing to an elevated risk of venous thromboembolism. In recent years, post hoc analyses of randomized clinical trials and real-world safety data have raised concerns about a potentially different thrombotic risk profile between patients treated with Janus kinase inhibitors (JAKi) and those receiving tumor necrosis factor inhibitors (TNFi). Nevertheless, the precise effects of these therapeutic strategies on global coagulation dynamics in whole blood, as well as on platelet function, remain incompletely understood and warrant further investigation. The aim of this study was to compare viscoelastic coagulation properties and platelet reactivity among RA patients treated with JAK inhibitors or TNF inhibitors and to evaluate differences relative to healthy control subjects (HC) in order to better characterize treatment-related prothrombotic profiles.
Methods. This was a single-center observational study including RA patients receiving stable treatment with either JAKi or TNFi for at least three months. All participants underwent assessment of coagulation and platelet function using whole-blood rotational thromboelastometry (ROTEM^®) and impedance aggregometry (MULTIPLATE^®). The primary endpoints were the evaluation of: (a) whole-blood thrombogenic potential, assessed through viscoelastic clot parameters, and (b) platelet reactivity in response to specific agonists. Multivariable linear regression models were applied to adjust for potential confounders, including age, body mass index (BMI), natural logarithm-transformed Simplified Disease Activity Index (SDAI), treatment group, and ln-transformed prednisone dose.
Results. A total of 61 RA patients (30 receiving JAKi and 31 receiving TNFi) and 34 healthy controls were included in the analysis. Compared with healthy individuals, RA patients demonstrated significantly increased maximum clot firmness (MCF) across all ROTEM assays, including INTEM (63.4±4.0 vs 57.2±4.1 mm), EXTEM (66.2±4.1 vs 55.9±4.7 mm), and FIBTEM (15.7±3.6 vs 12.4±3.7 mm), with all comparisons reaching statistical significance (p<0.001). In addition, platelet aggregation responses were significantly enhanced in RA patients across all tested pathways (p<0.001). In multivariable analyses, treatment with JAK inhibitors, compared with TNF inhibitors, was independently associated with higher EXTEM MCF (β=2.32, 95% CI 0.42–4.23; p=0.018) and FIBTEM MCF (β=1.72, 95% CI 0.07–3.37; p=0.041). Furthermore, prednisone dose emerged as an independent predictor of increased INTEM and EXTEM MCF, while disease activity, as measured by SDAI, was independently associated with enhanced ADP-induced platelet aggregation (β=11.34, 95% CI 4.31–18.37; p=0.002).
Conclusions. RA is associated with a prothrombotic phenotype characterized by increased clot firmness and heightened platelet reactivity. Treatment with JAK inhibitors appears to be independently associated with greater viscoelastic clot strength compared with TNF inhibitors. Additionally, systemic inflammation and glucocorticoid exposure represent key determinants of coagulation activation and platelet hyperreactivity, underscoring their central role in shaping thrombotic risk in this patient population.