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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5242-5250.
Prepublished online as a Blood First Edition Paper on March 8, 2007; DOI 10.1182/blood-2006-06-030619.
Previous Article | Next Article 
Submitted June 26, 2006
Accepted March 1, 2007
Human platelets synthesize and express functional tissue factor
Olga Panes, Valeria Matus, Claudia G. Saez, Teresa Quiroga, Jaime Pereira, and Diego Mezzano*
Department of Hematology-Oncology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
Department of Clinical Laboratory, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
* Corresponding author; email: dmezzano{at}med.puc.cl.
The source and significance of blood-borne tissue factor (TF) are controversial. TF-mRNA, protein and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Non-stimulated, monocyte-free platelets from most individuals expressed TF-mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of Mr ~47kDa with other bands of ~35 and ~60kDa) in non-stimulated platelet membranes, which also increased post-activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by FXa generation, was induced post-activation and inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [35S]-methionine into TF proteins of Mr ~47, ~35, and ~60kDa, more intensely after activation. Puromycin, but not actinomycin D or DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) inhibited TF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane but also supply their own TF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify and provide a more coherent formulation of the current cell-based model of hemostasis.

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