alexa Platelet and endothelial expression of clotting factors for the treatment of hemophilia.
Nephrology

Nephrology

Journal of Nephrology & Therapeutics

Author(s): Montgomery RR, Shi Q, Montgomery RR, Shi Q

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Abstract Hemostasis is achieved by the coordinate interaction of plasma, platelets, and vascular endothelium. Coagulation factors circulate in plasma with synthesis in liver and in endothelium. Interaction between Factor VIII (FVIII) and von Willebrand factor (VWF) in plasma is critically important, but there remains some question about whether this relationship is first established within the endothelial cell or in plasma. When FVIII is expressed with VWF in a cell that stores VWF, FVIII will also be stored and released. The manuscript will summarize some studies in which gene therapy exploits this relationship between VWF and FVIII to achieve hemostasis even in the presence of circulating inhibitory antibodies to FVIII. VWF is critical to this efficacy in the presence of inhibitors. Since FIX expression in platelets is effective for hemophilia B, efficacy in the presence of inhibitory antibodies to FIX was not achieved and emphasized the importance of VWF to the efficacy of platelet FVIII expression. These approaches have been studied in murine models but will need further study before this approach can be attempted clinically. Copyright © 2012. Published by Elsevier Ltd.
This article was published in Thromb Res and referenced in Journal of Nephrology & Therapeutics

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