Intravascular recovery of VWF and FVIII following intraperitoneal injection and differences from intravenous and subcutaneous injection in mice. Haemophilia 2012 Jul;18(4):639-46
Date
01/10/2012Pubmed ID
22221819Pubmed Central ID
PMC3323668DOI
10.1111/j.1365-2516.2011.02735.xScopus ID
2-s2.0-84863193826 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Intravenous infusion studies in humans suggest that both von Willebrand factor (VWF) and factor VIII (FVIII) remain intravascular in contrast to other coagulation proteins. We explored whether infusion of VWF and FVIII by either intraperitoneal (i.p.) or subcutaneous (s.c.) injection would result in efficient absorption of these large proteins into the vascular circulation. FVIII(null) or VWF(null) mice were infused with plasma-derived or recombinant VWF and/or FVIII by i.p., s.c., or intravenous (i.v.) injection. Both VWF and FVIII were absorbed into the blood circulation after i.p. injection with a peak between 2 and 4 h at levels similar to those observed in mice infused intravenously. In contrast, neither VWF nor FVIII was detected in the plasma following s.c. injection. Although i.v. injection achieved peak plasma levels quickly, both human VWF and FVIII rapidly decreased during the first 2 h following i.v. injection. Following both i.v. and i.p. infusion of VWF, the multimeric structure of circulating VWF was similar to that observed in the infusate. These results demonstrate that both VWF and FVIII can be efficiently absorbed into the blood circulation following i.p., but not s.c. injection, indicating that i.p. administration could be an alternative route for VWF or FVIII infusion.
Author List
Shi Q, Kuether EL, Schroeder JA, Fahs SA, Montgomery RRAuthors
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinQizhen Shi MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsFactor VIII
Injections, Intraperitoneal
Injections, Intravenous
Injections, Subcutaneous
Mice
Mice, Inbred C57BL
von Willebrand Factor
