title: Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis.
abstract: Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet generation, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 decades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug (i.e. the first wave of hemostasis). Activated platelets can also provide negatively charged phosphatidylserinerich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation (i.e. the second wave of hemostasis). Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-independent platelet aggregation and thrombosis, and the plasma fibronectin-mediated "protein wave" of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflammation and atherosclerosis and the potential strategies to control atherothrombosis.
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.|Jilin Provincial Center for Disease Control and Prevention, Changchun, Jilin, 130062 China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.|Canadian Blood Services, Toronto, Ontario M5B 1W8, Canada.
authors.forename: Naadiya
authors.initials: N
authors.lastname: Carrim
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.|Canadian Blood Services, Toronto, Ontario M5B 1W8, Canada.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.
authors.forename: Reid C
authors.initials: RC
authors.lastname: Gallant
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, M5B 1W8, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.|Department of Medicine and Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada. nih@smh.ca.
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
keywords: fibrinogen; fibronectin; integrin αIIbβ3; platelets; thrombosis and hemostasis