The Inflammatory Link of Rheumatoid Arthritis and Thrombosis: Pathogenic Molecular Circuits and Treatment Approaches

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation that primarily affects the joints but can also involve extra-articular organs. Its multifactorial etiology remains incompletely understood, necessitating further investigation into its underlying mechanisms. The primary therapeutic goal in RA management is to achieve disease remission or maintain low RA activity to prevent long-term morbidity. RA therapies aim to mitigate joint damage, reduce disability, and prevent systemic complications such as cardiovascular diseases. In addition to pharmacological treatments, non-pharmacological interventions-including physiotherapy, occupational therapy, and lifestyle modifications such as smoking cessation, regular exercise, and adherence to a balanced diet-play a crucial role in managing the disease. Beyond joint inflammation, RA has been strongly associated with an increased risk of thrombosis, contributing significantly to both morbidity and mortality. The link between RA and thrombotic events arises from a complex interplay of inflammatory pathways, endothelial dysfunction, and coagulation abnormalities. This review provides an in-depth analysis of the mechanisms driving the association between thrombo-inflammatory manifestations and the incidence of RA, the impact of RA treatment on thrombosis prevalence, and potential therapeutic strategies for managing both conditions concurrently. By integrating recent advancements in rheumatoid arthritis (RA) pathophysiology and thrombo-inflammatory research, this paper provides a comprehensive resource on the inflammatory link between RA and thrombosis while discussing and comparing current and emerging treatment approaches. Further investigation into these mechanisms could facilitate the development of targeted therapies that reduce the risk of thrombosis in patients with RA.

Keywords: DMARDs; anti-rheumatic drugs; anticoagulants; antithrombotic therapy; autoimmune diseases; inflammation; rheumatoid arthritis; thrombosis; venous thromboembolic events.

Figure 1

Thrombosis affiliation with rheumatoid arthritis (parts of this figure were obtained from https://smart.servier.com/, accessed on 10 December 2024).

Figure 2

Arterial and venous thromboembolic disorders (parts of this figure were obtained from https://smart.servier.com/, accessed on 11 December 2024).

Figure 3

Molecular mechanisms involved in thromboembolism (parts of this figure were obtained from https://smart.servier.com/, accessed on December 11 2024).

Figure 4

Role of platelets in thrombosis (parts of this figure were obtained from https://smart.servier.com/, accessed on 11 December 2024).

Figure 5

Mechanisms and risk factors of rheumatoid arthritis (parts of this figure were obtained from https://smart.servier.com/, accessed on 10 December 2024).

Figure 6

Virchow’s pyramid in patients with rheumatoid arthritis (parts of this figure were obtained from https://smart.servier.com/, accessed on 11 December 2024).

Figure 7

Commonly-used conventional synthetic, targeted synthetic, and biologic DMARDs (molecular structures were obtained from https://molview.org/, accessed on 12 December 2024, while schematic representations of antibodies were obtained from https://smart.servier.com/, accessed on 12 December 2024).