An engineered factor Va prevents bleeding induced by anticoagulant wt activated protein C.

ABSTRACT:

Objective

An increased risk of bleeding is observed in patients receiving activated protein C (APC), which may be a limiting factor for the application of novel APC therapies. Since APC's therapeutic effects often require its cytoprotective activities on cells but not APC's anticoagulant activities, an agent that specifically antagonizes APC's anticoagulant effects but not its cytoprotective effects could provide an effective means to control concerns for risk of bleeding. We hypothesized that superFVa, an engineered activated FVa-variant that restores hemostasis in hemophilia could reduce APC-induced bleeding.

Approach and results

SuperFVa was engineered with mutations of the APC cleavage sites (Arg506/306/679Gln) and a disulfide bond (Cys609-Cys1691) between the A2 and A3

SUBMITTER: von Drygalski A 

PROVIDER: S-EPMC4134195 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature