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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-04-1224.

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2003-04-1224v1
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Submitted April 18, 2003
Accepted June 6, 2003

Biosynthetic origin and functional significance of murine platelet factor V

Tony L Yang, Steven W Pipe, Angela Yang, and David Ginsburg*

Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA

* Corresponding author; email: ginsburg{at}umich.edu.

Factor V (FV), a central regulatory protein in hemostasis, is distributed into distinct plasma and platelet compartments. Though platelet FV is highly concentrated within the platelet {alpha}-granule, previous analysis of human bone marrow and liver transplant recipients has demonstrated that platelet FV in these individuals originates entirely from the uptake of plasma FV. In order to examine further the biosynthetic origins of the platelet and plasma FV pools, we performed bone marrow transplants of Fv-null (Fv-/-) fetal liver cells (FLCs) into wildtype mice. Fractionation of whole blood from control mice demonstrated that ~14% of total blood FV activity is platelet-associated. Mice transplanted with Fv-null FLCs displayed a high degree of engraftment and appeared grossly normal, with no evidence for spontaneous hemorrhage. Though total FV levels in Fv-null FLC recipients were only mildly decreased, the FV activity within the platelet compartment was reduced to <1% of that in normal mice. We conclude that the murine platelet FV compartment is derived exclusively from primary biosynthesis within cells of marrow origin, presumably megakaryocytes, and that an intact platelet FV pool is not required for protection from spontaneous hemorrhage or bleeding following minor trauma.


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