title: Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies.
abstract: Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i.e. the classical first wave of hemostasis). These three waves of hemostasis, in the event of atherosclerotic plaque rupture, may turn pathogenic, and cause uncontrolled vessel occlusion and thrombotic disorders (e.g. heart attack and stroke). Current anti-platelet therapies have significantly reduced cardiovascular mortality, however, on-treatment thrombotic events, thrombocytopenia, and bleeding complications are still major concerns that continue to motivate innovation and drive therapeutic advances. Emerging evidence has brought platelet adhesion molecules back into the spotlight as targets for the development of novel anti-thrombotic agents. These potential antiplatelet targets mainly include the platelet receptors glycoprotein (GP) Ib-IX-V complex, β3 integrins (αIIb subunit and PSI domain of β3 subunit) and GPVI. Numerous efforts have been made aiming to balance the efficacy of inhibiting thrombosis without compromising hemostasis. This mini-review will update the mechanisms of thrombosis and the current state of antiplatelet therapies, and will focus on platelet adhesion molecules and the novel anti-thrombotic therapies that target them.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada ; Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong People's Republic of China.
authors.forename: Xiaohong Ruby
authors.initials: XR
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada ; Canadian Blood Services, Toronto, ON Canada.
authors.forename: Naadiya
authors.initials: N
authors.lastname: Carrim
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada.
authors.forename: Miguel Antonio Dias
authors.initials: MA
authors.lastname: Neves
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: McKeown
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada.
authors.forename: Tyler W
authors.initials: TW
authors.lastname: Stratton
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada.
authors.forename: Rodrigo Matos Pinto
authors.initials: RM
authors.lastname: Coelho
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada ; Canadian Blood Services, Toronto, ON Canada.
authors.forename: Pingguo
authors.initials: P
authors.lastname: Chen
authors.affiliation: CCOA Therapeutics Inc, Toronto, ON Canada.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: Lee's Pharmaceutical holdings limited, Shatin Hong Kong, China ; Zhaoke Pharmaceutical co. limited, Hefei, Anhui China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Dai
authors.affiliation: Lee's Pharmaceutical holdings limited, Shatin Hong Kong, China ; Zhaoke Pharmaceutical co. limited, Hefei, Anhui China ; Hong Kong University of Science and technology, Hong Kong, China.
authors.forename: Benjamin Xiaoyi
authors.initials: BX
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada ; Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada ; Canadian Blood Services, Toronto, ON Canada ; CCOA Therapeutics Inc, Toronto, ON Canada ; Department of Medicine and Department of Physiology, University of Toronto, Toronto, ON Canada.
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
keywords: Anfibatide; GPIbα; GPVI; Hemostasis; Integrins; P-selectin; Stroke; Thrombosis; αIIbβ3