Interactions of platelet subpopulations and their relevance to anti-platelet therapy

• Grant number: 14/04478-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): September 22, 2014
• Effective date (End): September 21, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Plinio Minghin Freitas Ferreira
• Supervisor: Timothy David Warner
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Queen Mary University of London, England
• Associated to the scholarship: 13/04994-0 - Smooth muscle contraction mechanisms of Epicrates chencria and Boa constrictor, BP.DD

Abstract

Aspirin, often together with a P2Y12 receptor blocker, is used as anti-thrombotic protection for patients at risk of heart attacks and strokes. However, despite these drugs many patients still have an elevated risk of thrombosis. Aspirin and the most widely used P2Y12 receptor blockers are pharmacokinetically short-lived but permanently inhibit circulating platelets. In healthy individuals platelets survive in the circulation for around 7-10 days, but this survival time is reduced in certain conditions, e.g. diabetes, in which there is a greater proportion of platelets newly released from megakaryocytes and greater risk of thrombosis. The relative significances of inhibited (circulating) and uninhibited (newly released) platelets in the formation of platelet thrombi are unexplored. This project will use a range of in vitro and ex vivo studies to understand how these different platelet populations interact in the formation of thrombi and contribute to the failure of anti-thrombotic therapy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KNOWLES, REBECCA B.; LAWRENCE, MATTHEW J.; FERREIRA, PLINIO M.; HAYMAN, MELISSA A.; D'SILVA, LINDSAY A.; STANFORD, SOPHIE N.; SABRA, AHMED; TUCKER, ARTHUR T.; HAWKINS, KARL M.; WILLIAMS, PHYLIP R.; et al. Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties. PLATELETS, v. 29, n. 2, p. 162-170, 2018. (14/04478-5)

ARMSTRONG, PAUL C.; FERREIRA, PLINIO M.; CHAN, MELISSA V.; LUNDBERG SLINGSBY, MARTINA H.; CRESCENTE, MARILENA; SHIH, CHIH-CHIN; KIRKBY, NICHOLAS S.; HOBBS, ADRIAN J.; WARNER, TIMOTHY D.. Combination of cyclic nucleotide modulators with P2Y(12) receptor antagonists as anti-platelet therapy. Journal of Thrombosis and Haemostasis, v. 18, n. 7, MAY 2020. (14/04478-5)