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
Based on our work and that of many other workers, we have developed
a model of coagulation in vivo. Many workers have demonstrated
mechanisms by which cells can influence the coagulation process.
Nonetheless, the prevailing view of hemostasis remains that the protein
coagulation factors direct and control the process with cells serving
primarily to provide a phosphatidylserine containing surface on which
the procoagulant complexes are assembled. By contrast, we propose a
model in which coagulation is regulated by properties of cell surfaces.
This model emphasizes the importance of specific cellular receptors for
the coagulation proteins. Thus, cells with similar phosphatidylserine
content can play very different roles in hemostasis depending on their
complement of surface receptors. We propose that coagulation occurs
not as a “cascade”, but in three overlapping stages: 1) initiation, which
occurs on a tissue factor bearing cell; 2) amplification, in which platelets
and cofactors are activated to set the stage for large scale thrombin
generation; and 3) propagation, in which large amounts of thrombin are
generated on the platelet surface. This cell based model explains some
aspects of hemostasis that a protein-centric model does not.