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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4674-4676. Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-12-4701.
Submitted December 13, 2004
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA * Corresponding author; email: poncz{at}email.chop.edu.
We have previously reported that ectopically expressed Factor (F) VIII is stored within platelets and is released upon platelet activation. Studies in various cell lines by others have suggested that having Von Willebrand Factor (VWF) coexpression was necessary for FVIII granular storage and for its secretion. We tested the importance of VWF coexpression for ectopic storage of FVIII in platelets and for its bioavailability. Transgenic mice expressing platelet-specific FVIII were crossed onto a VWF-/- background. Antigenic levels of platelet FVIII in these mice were nearly unchanged whether VWF was present or not. Whole blood clotting times and FeCl3 carotid artery injury correction demonstrated that platelet FVIII demonstrably improved the bleeding diathesis in FVIIInull mice independent of the platelets' VWF status. Immunogold electron microscopy demonstrated that platelet FVIII is stored in platelet
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