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Prepublished online as a Blood First Edition Paper on July 31, 2003July 24, 2003; DOI 10.1182/blood-2003-05-1519. This Article Full Text (PDF) All Versions of this Article: 2003-05-1519v1 2003-05-1519v2 102/12/4006    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yaravoi, H. Articles by Poncz, M. Search for Related Content PubMed PubMed Citation Articles by Yaravoi, H. Articles by Poncz, M. Social Bookmarking                   What's this? Submitted May 16, 2003 Accepted July 7, 2003 Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment Helen Yaravoi, Dubravka Kufrin, Don E Eslin, Michael A Thornton, Sandra L Haberichter, Qizhen Shi, Hua Zhu, Rodney Camire, Steve S Fakharzadeh, M Anna Kowalska, David A Wilcox, Bruce S Sachais, Robert R Montgomery, and Mortimer Poncz* Department of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Department of Hematology, Medical College of Wisconsin, Milwaukee, WI, USA Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA * Corresponding author; email: poncz{at}email.chop.edu. Activated platelets release their granule content in a concentrated fashion at sites of injury. We examined whether ectopically expressed Factor VIII in developing megakaryocytes would be stored in -granules and whether its release from circulating platelets would effectively ameliorate bleeding in a Factor VIIInull mice model. Using the proximal Glycoprotein 1b promoter to drive expression of a human Factor VIII cDNA construct, transgenic lines were established. One line had detectable human Factor VIII that colocalizes with von Willebrand Factor in platelets. These animals had platelet Factor VIII levels equivalent to 3-9% plasma levels, although there was no concurrent plasma human FVIII detectable. When crossed onto a Factor VIIInull background, whole blood clotting time was partially corrected in Line #38, equivalent to a 3% correction level. In a cuticular bleeding time study, these animals also had only a partial correction, but in a FeCl3 carotid artery thrombosis assay, correction was equivalent to a 50-100% level. These studies show that Factor VIII can be expressed and stored in platelet -granules. Our studies also suggest that platelet-released Factor VIII is at least as potent as an equivalent plasma level and perhaps even more potent in an arterial thrombosis model. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Pan, T. Liu, J.-Y. Kim, D. Zhu, C. Patel, Z.-H. Cui, X. Zhang, J. O. Newgren, A. Reames, D. Canivel, et al. Enhanced efficacy of recombinant FVIII in noncovalent complex with PEGylated liposome in hemophilia A mice Blood, September 24, 2009; 114(13): 2802 - 2811. [Abstract] [Full Text] [PDF] R. Blue, M. A. Kowalska, J. Hirsch, M. Murcia, C. A. Janczak, A. Harrington, M. Jirouskova, J. Li, R. Fuentes, M. A. Thornton, et al. 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