From the Guidelines
Yes, rheumatoid arthritis (RA) can cause hypercoagulability, increasing the risk of blood clots, as evidenced by the prothrombotic state mentioned in the 2012 European guidelines on cardiovascular disease prevention in clinical practice 1. This hypercoagulable state in RA patients results from chronic inflammation, which activates the coagulation system and suppresses natural anticoagulant mechanisms. Inflammatory cytokines like TNF-alpha, IL-1, and IL-6 promote tissue factor expression, platelet activation, and endothelial dysfunction, all contributing to a prothrombotic environment. Additionally, RA patients often have elevated fibrinogen levels, increased platelet counts, and higher levels of von Willebrand factor. The risk of thrombotic events is particularly elevated during disease flares when inflammation is most pronounced. Some medications used to treat RA, such as corticosteroids at higher doses, may further increase clotting risk, while others like JAK inhibitors (tofacitinib, baricitinib) carry boxed warnings about thrombosis risk. However, effective control of RA inflammation with appropriate disease-modifying antirheumatic drugs (DMARDs) like methotrexate or biologics can help reduce this hypercoagulable state by addressing the underlying inflammatory process, as supported by the 2020 lipid management in rheumatoid arthritis position paper of the European Society of Cardiology 1. Key points to consider include:
- The increased risk of cardiovascular morbidity and mortality in RA patients, with a 50% increase in cardiovascular events 1
- The potential for certain RA treatments to influence clotting risk, such as NSAIDs and cyclo-oxygenase-2 inhibitors, which may have prothrombotic effects 1
- The importance of managing cardiovascular risk factors in RA patients, including the use of statins and aspirin, as discussed in the 2014 guidelines for the primary prevention of stroke 1 Overall, the management of RA should include consideration of the potential for hypercoagulability and the implementation of strategies to reduce this risk, prioritizing the reduction of morbidity, mortality, and improvement of quality of life.
From the Research
Rheumatoid Arthritis and Hypercoagulability
- Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease, which may be related to hypercoagulability 2, 3.
- Studies have shown that patients with RA have higher levels of prothrombotic biomarkers, such as prothrombin fragment 1+2 (F1+2) and D-dimer, compared to healthy controls 4.
- The use of tumor necrosis factor (TNF)-alpha blocking agents, such as infliximab, has been shown to decrease inflammation and coagulation biomarkers in RA patients, which may help reduce the risk of thrombotic events 4.
- The chronic inflammatory state in RA is thought to contribute to accelerated atherogenesis and increased cardiovascular risk, independent of traditional risk factors 2, 5, 3.
- The role of inflammation in atherosclerosis associated with RA is supported by the involvement of common proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and TNF-alpha, in the development and progression of both RA and atherosclerosis 3.
Mechanisms and Risk Factors
- The pathogenic mechanisms underlying the increased cardiovascular risk in RA patients include pro-oxidative dyslipidemia, insulin resistance, prothrombotic state, hyperhomocysteinemia, and immune mechanisms such as T-cell activation 2.
- The use of certain medications, such as corticosteroids and antimalarials, may have beneficial or adverse effects on cardiovascular risk factors in RA patients 6.
- Statins, which are commonly used to reduce LDL-cholesterol levels, may also exert immunomodulatory effects that could be beneficial in reducing cardiovascular risk in RA patients 5.