Whole-blood coagulation and platelet dynamics identify differential prothrombotic states in patients with rheumatoid arthritis treated with JAK or TNF-ɑ inhibitors.

Authors

Alessandro Giollo, Lorenzo Di Luozzo, Mariangela Salvato, Kiren Khalid, Riccardo D'Andrea, Andrea Benetti, Chiara Samà, Roberta Ramonda, Paolo Simioni, Luca Spiezia

Published in

RMD open. Volume 12. Issue 3. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Rheumatoid arthritis (RA) is associated with inflammation-driven hypercoagulability and increased venous thromboembolic risk. Post hoc analyses of safety trials have raised concerns regarding a potential differential thrombotic risk with Janus kinase inhibitors (JAKi) compared with tumour necrosis factor inhibitors (TNFi).
To compare viscoelastic coagulation profiles and platelet reactivity in patients with RA treated with JAKi or TNFi, and in healthy controls (HC).
In this single-centre observational study, patients with RA with stable JAKi or TNFi therapy (>3 months) underwent whole-blood rotational thromboelastometry (ROTEM) and impedance aggregometry (MULTIPLATE). The primary outcomes were evaluation of: (a) whole-blood thrombogenic potential and (b) platelet reactivity. Multivariable linear regression adjusted for age, body mass index, ln-transformed Simple Disease Activity Index, treatment group and ln-transformed prednisone dose.
Sixty-one patients with RA (30 JAKi, 31 TNFi) and 34 HC were included. Compared with HC, patients with RA exhibited significantly higher maximum clot firmness (MCF) across all ROTEM assays (INTEM 63.4±4.0 vs 57.2±4.1 mm; EXTEM 66.2±4.1 vs 55.9±4.7 mm; FIBTEM 15.7±3.6 vs 12.4±3.7 mm; all p<0.001) and enhanced platelet aggregation (all p<0.001). In multivariable analyses, JAKi therapy (vs TNFi) was independently associated with higher EXTEM MCF (β=2.32, 95% CI 0.42 to 4.23; p=0.018) and FIBTEM MCF (β=1.72, 95% CI 0.07 to 3.37; p=0.041). Prednisone dose independently predicted INTEM and EXTEM MCF, while SDAI independently predicted ADP-induced aggregation (β=11.34, 95% CI 4.31 to 18.37; p=0.002).
RA is characterised by enhanced clot firmness and platelet reactivity. JAKi therapy was independently associated with higher viscoelastic clot strength compared with TNFi, while inflammatory burden and glucocorticoid exposure were key determinants of prothrombotic signatures.

PMID:
42575539
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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