Lack of desmopressin (DDAVP) response in men with hemophilia A following liver transplantation.

Abstract

Although hemophilia A, a congenital disorder caused by defective or deficient factor VIII:C (FVIII), is cured by liver transplantation, the exact site of hepatic FVIII production is unknown. Further, while intracellular co-localization of FVIII and von Willebrand factor (VWF) is required for in vitro FVIII secretion, whether it is required for in vivo FVIII secretion is not known. An ideal setting to study this problem is in individuals with hemophilia A following liver transplantation, as their FVIII is synthesized primarily in hepatic, but not extrahepatic endothelial cells, while VWF is synthesized primarily in extrahepatic vascular endothelium. Following liver transplantation for end-stage liver disease, three hemophilic men showed VWF, but no FVIII response to (DDAVP) infusion. By contrast, both VWF and FVIII increased in a non-hemophilic transplant recipient after DDAVP. These findings support a model in which intracellular co-localization of FVIII and VWF is necessary for in vivo FVIII secretion after DDAVP.

• Authors: P A Lamont, M V Ragni
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 3 Issue 10 Pg. 2259-63 (Oct 2005) ISSN: 1538-7933 [Print] England
• PMID: 16194203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• von Willebrand Factor
• Factor VIII
• Deamino Arginine Vasopressin

Topics

• Adult
• Deamino Arginine Vasopressin (administration & dosage, pharmacology)
• Factor VIII (biosynthesis, drug effects, metabolism)
• Hemophilia A (drug therapy, therapy)
• Humans
• Liver (metabolism)
• Liver Transplantation
• Male
• Middle Aged
• Protein Binding
• von Willebrand Factor (drug effects, metabolism)