Evaluation of the haemostatic potential of factor VIII‐heparin cofactor II hybrid proteins in a mouse model

Summary.  We constructed factor VIII‐heparin cofactor II (FVIII‐HCII) hybrid molecules, which are more readily activated by thrombin in vitro than the respective wild‐type molecules. The hybrid proteins were tested in a murine model of haemophilia A to investigate their haemostatic efficacy in vivo. Bleeding characteristics, measured using standard tail‐tip cutting techniques, were total blood loss, bleeding time and survival rate. FVIII‐HCII hybrids were found to be effective in preventing bleeding in FVIII knockout mice. While in vitro experiments showed that the chimaeric molecules had higher haemostatic functions than the wild‐type proteins, the variables analysed in vivo were similar for both proteins.