Activated platelets in multiple sclerosis: Immunoinflammatory mechanisms and the therapeutic controversy of acetylsalicylic acid.
TL;DR
A narrative review explores how platelet activation may contribute to MS through blood-brain barrier dysfunction, immune-cell recruitment, oxidative stress, demyelination, and neurodegeneration, and critically examines acetylsalicylic acid (ASA) as a potential platelet-targeted strategy.
Abstract
Platelets have emerged as participants in immune and inflammatory processes in multiple sclerosis (MS), extending their role beyond hemostasis. This narrative review explores how platelet activation may contribute to MS through blood-brain barrier (BBB) dysfunction, immune-cell recruitment, oxidative stress, demyelination, and neurodegeneration, and critically examines acetylsalicylic acid (ASA) as a potential platelet-targeted strategy. Evidence from experimental autoimmune encephalomyelitis (EAE) indicates that ASA may inhibit cyclooxygenase-1 (COX-1)-dependent thromboxane A₂ (TXA₂) synthesis, reduce platelet activation and neuroinflammatory signaling, influence T-cell responses, and support remyelination. Human evidence remains limited and heterogeneous, although observational studies support altered platelet activation and platelet-related biomarkers in MS, while small interventional studies suggest possible symptomatic effects of ASA on fatigue and exercise-associated thermoregulation. However, ASA may increase bleeding risk, including intracranial bleeding and may adversely affect mitochondrial function and oxidative balance. By integrating mechanistic, preclinical, and clinical findings, this review highlights the therapeutic controversy surrounding ASA and identifies key uncertainties regarding dose, patient selection, MS phenotype, and safety that require clarification in future clinical studies overall.