Platelets, leukocytes, and coagulation.
Considerable data now support the hypothesis that platelets actively regulate the propagation of coagulation by (1) expressing specific, high-affinity receptors for coagulation proteases, zymogens, and cofactors; (2) protecting the bound coagulation enzymes from inactivation/inhibition; (3) restricting coagulant activity to the site of vascular injury; and (4) amplifying the initiating stimulus to lead to explosive thrombin generation. Thrombin generation is sustained at the site of vascular injury by the recruitment of circulating monocytes and neutrophils to the growing thrombus via the interaction of PSGL-1, which is constitutively expressed by leukocytes, with P-selectin, which is expressed by activated platelets. Unique among cells, monocytes can provide the appropriate membrane surface for the assembly and function of all the coagulation complexes required for tissue factor-initiated thrombin production. More studies are required to further delineate the roles of neutrophils and lymphocytes in the procoagulant response. This review will discuss the recent investigations and controversies regarding the various mechanisms by which platelets and leukocytes function in, and regulate, thrombin generation.
Bouchard
B A
BA
Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405-0068, USA. bbouchar@zoo.uvm.edu
Tracy
P B
PB
D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D046911:Macromolecular Substances; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology; D015539:Platelet Activation; D013917:Thrombin / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D046911:Macromolecular Substances; D013917:Thrombin