Platelet aggregation signaling pathway

The platelet aggregation signaling pathway is a multi-step biological process critical for primary hemostasis and the maintenance of vascular integrity (StatPearls, 2023: https://www.ncbi.nlm.nih.gov/books/NBK553137/). Upon blood vessel injury, platelets are recruited to the subendothelial matrix where they undergo activation via receptors for collagen, thrombin, and ADP, leading to a conformational change in the Glycoprotein IIb/IIIa receptor (KEGG, 2024: https://www.genome.jp/kegg-bin/show_pathway?hsa04611). This change allows fibrinogen to bridge adjacent platelets, forming a stable aggregate or thrombus (Journal of Thrombosis and Haemostasis, 2015: https://doi.org/10.1111/jth.12957). Pathological over-activation of this pathway is a central mechanism in the development of acute coronary syndromes and ischemic strokes (Nature Reviews Cardiology, 2010: https://www.nature.com/articles/nrd3145). Consequently, various components of this pathway are major therapeutic targets for antiplatelet drugs, which aim to reduce thrombotic risk while balancing the potential for adverse bleeding events (PubMed, 2021: https://pubmed.ncbi.nlm.nih.gov/33616301/).

Other names

Platelet activation pathwayHemostasis signaling pathwayThrombosis signaling cascade

Antiplatelet drugs modulate this pathway by inhibiting specific signaling nodes, such as the production of thromboxane A2 by Cyclooxygenase-1, the binding of ADP to P2Y12 receptors, or the final common pathway of fibrinogen binding to Glycoprotein IIb/IIIa receptors (StatPearls, 2023: https://www.ncbi.nlm.nih.gov/books/NBK553137/).