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Blood, 1 July 2006, Vol. 108, No. 1, pp. 57-62. Prepublished online as a Blood First Edition Paper on March 23, 2006; DOI 10.1182/blood-2005-02-0788. This Article Full Text (PDF) All Versions of this Article: 2005-02-0788v1 108/1/57    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 Lovejoy, A. E Articles by Nugent, D. J Search for Related Content PubMed PubMed Citation Articles by Lovejoy, A. E Articles by Nugent, D. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 25, 2005 Accepted February 9, 2006 Safety and pharmacokinetics of recombinant Factor XIII-A2 administration in subjects with Factor XIII deficiency Amy E Lovejoy*, Tom C Reynolds, Jennifer E Visich, Michael D Butine, Guy Young, Melissa A Belvedere, Rachelle C Blain, Susan M Pederson, Laura M Ishak, and Diane J Nugent Department of Hematology, Children's Hospital of Orange County, Orange, CA, USA ZymoGenetics, Inc., Seattle, WA, USA * Corresponding author; email: alovejoy{at}chsd.org. Congenital Factor XIII (FXIII) deficiency is associated with a severe bleeding tendency, spontaneous abortion, and a high rate of spontaneous intracranial hemorrhage. This phase I escalating dose study was developed to evaluate the safety and pharmacokinetics of a single administration of human recombinant Factor XIII-A2 homodimer in adults with congenital FXIII deficiency. Pharmacokinetics and activity of recombinant FXIII (rFXIII) as well as changes in endogenous B subunit levels were assessed. Recombinant FXIII-A2 homodimer complexed with endogenous FXIII-B subunits to form a FXIII-A2B2 heterotetramer with a half-life of 8.5 days, similar to endogenous FXIII. The median dose-response was a 2.4% increase in FXIII activity per U/kg rFXIII administered. After administration of rFXIII-A2, clot solubility normalized as measured by clot lysis in urea. Clot strength and resistance to fibrinolysis, as assessed by thromboelastography, also improved. Safety reviews were conducted prior to each dose escalation and no serious adverse events, including bleeding or thrombosis, were noted during the study. In addition, there was no evidence of generation of specific antibodies to rFXIII or yeast proteins. Recombinant FXIII appears to be a safe and potentially effective alternative for factor XIII replacement in deficient subjects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-P. Fermand Initial Therapy for Multiple Myeloma: Role of Stem Cell Transplantation ASCO Educational Book, January 1, 2008; 2008(1): 375 - 379. [Abstract] [Full Text] [PDF] M. Attal, P. Moreau, H. Avet-Loiseau, and J.-L. Harousseau Stem Cell Transplantation in Multiple Myeloma Hematology, January 1, 2007; 2007(1): 311 - 316. [Abstract] [Full Text] [PDF]

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