A Cell-based Model of Hemostasis
Maureane Hoffman, Dougald M. Monroe III
Pathology and Laboratory Medicine Service, Durham VA and Duke University Medical Centers, Durham, NC, USA, and Division of Hematology/Oncology, Department of Medicine, The University of North Carolina, Chapel Hill, NC, USA
Summary Based on our work and that of many other workers, we have developeda model of coagulation in vivo. Many workers have demonstratedmechanisms by which cells can influence the coagulation process.Nonetheless, the prevailing view of hemostasis remains that the proteincoagulation factors direct and control the process with cells servingprimarily to provide a phosphatidylserine containing surface on whichthe procoagulant complexes are assembled. By contrast, we propose amodel in which coagulation is regulated by properties of cell surfaces.This model emphasizes the importance of specific cellular receptors forthe coagulation proteins. Thus, cells with similar phosphatidylserinecontent can play very different roles in hemostasis depending on theircomplement of surface receptors. We propose that coagulation occursnot as a “cascade”, but in three overlapping stages: 1) initiation, whichoccurs on a tissue factor bearing cell; 2) amplification, in which plateletsand cofactors are activated to set the stage for large scale thrombingeneration; and 3) propagation, in which large amounts of thrombin aregenerated on the platelet surface. This cell based model explains someaspects of hemostasis that a protein-centric model does not.