Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the...Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. 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 phosphatidylserine- rich 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-inde- pendent 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 inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.展开更多
Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloim...Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy.Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal alloimmunization.FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage.Proper diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies.Given the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT.The aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.展开更多
基金supported in part by Canadian Institutes of Health Research(MOP 119540),National Natural Science Foundation of China-Canadian Institutes of Health Research(China-Canada Joint Health Research Initiative Program),Heart and Stroke Foundation of Canada(Ontario)supported by equipment Funds from St.Michael's Hospital,Canadian Blood Services,and Canada Foundation for Innovation
文摘Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. 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 phosphatidylserine- rich 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-inde- pendent 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 inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.
基金This work was supported by Canadian Institutes of Health Research(MOP 68986,MOP 119551,MOP 97918,and 119540)。
文摘Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy.Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal alloimmunization.FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage.Proper diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies.Given the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT.The aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.
