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Manfredi et al1 explore the relationship between tumour necrosis factor α (TNFα), TNFα inhibition and platelet activation in rheumatoid arthritis (RA). Using elegant systems they demonstrate that TNFα activates platelets and promotes their proinflammatory and procoagulant actions, while TNF inhibition (TNFi) prevents platelet activation. They suggest this is a potential mechanism explaining why TNFi associates with a reduction of cardiovascular (CV) events in patients with RA, as shown in some observational studies. Should we then be(come) interested in platelet biology in RA?
The potential role of platelets in the pathogenesis of RA and related comorbidities has, in fact, received much less attention than it deserves. Platelets are small (1–2 μm) anucleate cells that are intimately involved in thrombosis, angiogenesis, bone remodelling, inflammation and autoimmunity. Their bidirectional, damaging and protective roles across pathophysiological processes have been explored in several clinical and laboratory studies. The discovery of specific platelet markers and agonists, which target a range of membrane-bound receptors, has resulted in better understanding of their role. It is now clear that platelet reactivity throughout their short lifespan (8–10 days) is determined by megakaryopoiesis, which is regulated quantitatively by thrombopoietin; any chemical compound targeting the maturation of platelet precursors in the bone marrow either directly or indirectly can alter the thrombotic, immune and inflammatory potential of circulating platelets.2 ,3
Activated platelets shed highly active membranous structures—microparticles—and transform from disc-shaped to enlarged cells with pseudopods that facilitate their interaction with other platelets, neutrophils, lymphocytes and other immune cells. Circulating neutrophils, in turn, interact with activated platelets to boost their ‘thromboinflammatory’ potential.4 Circulating cellular complexes of platelets are often found in the blood stream of patients with inflammatory conditions, such as RA, and it is suggested that platelet-derived microparticles along with other biological agents play a more important role in the development …
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