CO:02:4 | Whole blood hypercoagulable profiles in patients with rheumatoid arthritis

Lorenzo Di Luozzo¹, Alessandro Giollo¹, Mariangela Salvato¹, Francesca Frizzera¹, Kiren Khalid¹, Luca Spiezia², Andrea Benetti², Chiara Samà², Paolo Simioni², Andrea Doria¹. | ^1Unità di Reumatologia, Azienda Ospedaliera di Padova; ²Dipartimento di Medicina, Università di Padova, Italy

Background: Rheumatoid arthritis (RA)-associated disease activity is accompanied by abnormalities in the coagulation-fibrinolysis system, potentially increasing the risk of venous and arterial thromboembolism. The aim of this case-control study was to evaluate the hemostatic system functions in a group of RA patients by whole blood rotation thromboelastometry and impedance aggregometry.

Methods: Whole blood rotation thromboelastometry and impedance aggregometry were performed in RA patients (cases) treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and compared 1:1 with age (± 3 yrs) and sex-matched healthy individuals (controls). In each enrolled participant, global coagulation monitoring was assessed by whole blood rotational thromboelastometry (ROTEM^®, Instrumentation Laboratory-Werfen) and whole blood impedance aggregometry (Multiplate^® Analyser, Roche Diagnostics) tests. Variables assessing disease activity, demographics and cardiovascular risk were assessed. Univariate analyses (independent T-test, Pearson correlation) were performed.

Results: The study population included 30 RA patients on b/tsDMARDs and 30 controls. The cases (mean age 56.2±11.6 years, 90% female) had a mean disease duration of 17.8±9.1 years; most received methotrexate (60%) and low-dose prednisone (1.2±2.1 mg/day); NSAIDs were used by 47%. No participants were taking antiplatelet or anticoagulant medications. Disease activity and inflammatory markers were generally low (SDAI: 10.1±8, CRP 3.5±4.3 mg/L, ESR 23±18.5 mm/h). A history of VTE was reported in 7% of patients, while no previous MACE events were documented. Regarding cardiovascular risk factors: 10% were current smokers, 53% had hypercholesterolaemia, 27% had hypertension and only one patient had diabetes mellitus. Thromboelastometry and aggregometry showed excellent internal validity, as several measurements significantly and strongly correlated with inflammatory markers, disease activity, and lipids (Figure 1). In INTEM, EXTEM and FIBTEM tests, maximum clot firmness (MCF) was significantly increased in RA patients compared with controls (p<0.001 in all three comparisons) (Table 1). A significant difference in platelet aggregation was found between RA patients and healthy controls in each of the tests considered (Table 1). Patients taking glucocorticoids at the time of blood sampling had MCF in INTEM and EXTEM significantly higher than those patients who were not (p=0.011 and p=0.020, respectively; Table 2). Thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly higher in patients taking oral glucocorticoids than in those who were not (p=0.0006; Table 2). Use of NSAIDs did not affect outcomes. Analysis of data stratified by type of drug used is still in progress.

Conclusions: Hypercoagulability can be detected by whole blood thromboelastometry and impedance aggregometry in RA patients and correlates with disease activity. The clinical implication of these findings deserves further investigations.