The Role of Coagulation in Chronic Inflammatory Disorders: A Jack of All Trades

Abstract

Chronic inflammatory disorders constitute a heterogeneous group of complex and multifactorial diseases, which are often associated with increased cardiovascular morbidity and mortality, independent of the established cardiovascular risk factors. In keeping with this observation, hypercoagulability is frequently observed in patients suffering from atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis although the physiological significance of activated coagulation remained elusive. However, the identification of protease activated receptors (PAR) seem to provide a link between coagulation activation and disease progression as their activation by coagulation factors triggers a broad range of signaling pathways relevant for chronic inflammatory disorders. In experimental animal models, anticoagulation and/or genetic ablation of PAR signaling affords protection against the perpetuation of atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis. It is thus tempting to speculate that targeting the coagulation-PAR axis might have clinical relevance in the setting of chronic inflammatory disorders. In the current review, we discuss the current knowledge on coagulation activation in inflammatory disorders, we discuss the relationship between atherosclerosis, chronic obstructive pulmonary disease and rheumatoid arthritis and we review the current knowledge on PAR signaling in these disorders.

The risk of deep venous thrombosis and pulmonary embolism in giant cell arteritis: a general population-based study

“…Decreased mobility, especially during the initial period of the diagnoses before the onset of full treatment effects, may contribute to VTE through increased stasis of blood. Similarly, inflammatory conditions, like GCA, are associated with endothelial dysfunction,36 which is likely to be worse during the initial uncontrolled disease status. As inflammation, lipids and the immune system may play a role in venous thrombosis through a complex interplay, the level of inflammation may matter 37.…”

The risk of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a UK population-based outpatient cohort study

“…For example, inflammation modulates thrombotic responses by upregulating procoagulants, downregulating anticoagulants and suppressing fibrinolysis 12. Furthermore, inflammation is a key determinant of endothelial function in both arteries and veins,14 15 40 41 and chronic inflammatory disorders are associated with endothelial dysfunction,14 15 including RA 13. RA patients might have additional underlying VTE pathophysiology, such as inflammatory damage to the vessel wall due to venulitis or presence of antiphospholipid antibodies.…”

Temporal Trends of Venous Thromboembolism Risk Before and After Diagnosis of Giant Cell Arteritis

“…In certain vasculitides (e.g., Behçet's disease), venous inflammation may result in the expression of a localized prothrombotic phenotype . Under conditions in which no underlying venous angiitis is evident (e.g., rheumatoid arthritis), it is speculated that systemic inflammation not only causes widespread endothelial dysfunction, but also alters the balance between the coagulation and fibrinolytic systems, leading to generalized thrombophilic diathesis .…”