The contribution of platelets to the pathogenesis of Raynaud's phenomenon and systemic sclerosis

Raynaud's phenomenon (RP) describes the excessive vascular response of the digital vessels in response to cold exposure and emotional stress. It is typically the earliest manifestation of systemic sclerosis (SSc), a multisystem disease of unknown aetiology characterised by vasculopathy, inflammation and fibrosis. The biological actions of platelets are known to extend beyond primary haemostasis with a growing appreciation of their contribution to vascular function, inflammation and wound repair. This has led to a considerable body of work evaluating associations between platelet function analysis and RP/SSc. This review provides a conceptual framework upon which the potential contribution of platelets to vascular dysfunction, autoimmunity and tissue remodelling in RP and SSc is considered. We describe the existing evidence to support excessive platelet activation in RP and SSc, ranging from the early studies of platelet aggregability and circulating platelet-derived mediators, to the important findings of the recent work that has begun to explore the potential direct pathogenic role of platelets in established murine models of SSc. We shall describe and critically appraise the findings of previous therapeutic studies evaluating the use of anti-platelet agents in RP and SSc, along with their implications for future therapeutic intervention in these conditions.