Evaluation of the haemostatic potential of factor VIII-heparin cofactor II hybrid proteins in a mouse model.
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.
Schatz
Simone
S
Baxter BioScience, Biomedical Research Centre, Orth-Donau, Austria.
Turecek
Peter L
PL
Fiedler
Christian
C
Zimmermann
Klaus
K
Gritsch
Herbert
H
Voorberg
Jan
J
Schwarz
Hans Peter
HP
Dorner
Friedrich
F
Scheiflinger
Friedrich
F
D000818:Animals; D001760:Bleeding Time; D004338:Drug Combinations; D005169:Factor VIII / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D006470:Hemorrhage / Q000517:prevention & control; D006490:Hemostatics / Q000008:administration & dosage* / Q000378:metabolism; D015844:Heparin Cofactor II / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D015996:Survival Rate; D013917:Thrombin / Q000378:metabolism
D004338:Drug Combinations; D006490:Hemostatics; D011994:Recombinant Proteins; D015844:Heparin Cofactor II; D005169:Factor VIII; D013917:Thrombin