Improved hemostasis in hemophilia mice by means of an engineered factor Va mutant.

ABSTRACT:

Background

Factor (F)VIIa-based bypassing not always provides sufficient hemostasis in hemophilia.

Objectives

To investigate the potential of engineered activated factor V (FVa) variants as bypassing agents in hemophilia A.

Methods

Activity of FVa variants was studied in vitro using prothrombinase assays with purified components and in FV- and FVIII-deficient plasma using clotting and thrombin generation assays. In vivo bleed reduction after the tail clip was studied in hemophilia A mice.

Results and conclusions

FVa mutations included a disulfide bond connecting the A2 and A3 domains and ones that rendered FVa resistant to inactivation by activated protein C (APC). '(super) FVa,' a combination of the A2-A3 disulfide (A2-SS-A3) to stabilize FVa and of APC-cleava

SUBMITTER: von Drygalski A 

PROVIDER: S-EPMC4161283 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature