Physical Sciences and Mathematics Commons^™

Structural Characterization Of A Human/Porcine Chimeric Fviii Construct And An Improved Human Factor Viii Model And Progress Towards Determination Of The Fviii C1 Domain In Complex With Inhibitory Antibodies, Ian Smith

WWU Graduate School Collection

Blood coagulation factor VIII (FVIII) is a non-enzymatic protein cofactor, which plays a crucial role in the formation of a stable blood clot. Absence or deficiency of FVIII results in the blood disorder hemophilia A, with symptoms including internal hemorrhaging and the inability to stop bleeding from open wounds. Treatment of hemophilia A relies on replacement of FVIII with blood, plasma, or protein concentrate infusions. Unfortunately, approximately 30% of patients receiving replacement FVIII generate pathologic anti-FVIII inhibitory antibodies, which both reduce the effectiveness of the FVIII therapeutic and increase the severity of hemophilia A symptoms.

This thesis reports the determination …