Local application of recombinant active-site inhibited human clotting factor VIIa reduces thrombus weight and improves patency in a rabbit venous thrombosis model.
OBJECTIVE
To study whether locally administered recombinant inactivated human coagulation factor VIIa (FFR-rFVIIa) would reduce the thrombus formation and improve patency in an experimental venous thrombosis model without inducing systemic changes in the coagulation.


METHODS
Experimental double-dummy randomised study.


METHODS
In 20 healthy New Zealand White rabbits both jugular veins were exposed under general anaesthesia.


METHODS
The thrombi were induced in a 10 mm long jugular vein segment with a combination of chemical destruction of the intima and a restriction of the bloodflow. Each segment was treated with either FFR-rFVIIa or placebo injected directly into the vein.


RESULTS
1.5 mg topically applied FFR-rFVIIa significantly reduced the thrombus weight (p < 0.001). The 30 and the 120 min patency tests were significantly improved (p < 0.05 and p < 0.001, respectively) Plasma analyses (APTT, dilute-TF time, FVII protein) were evaluated as baseline, 3 min after declamping and at sacrifice. No prolongation of the clotting times were seen. FFR-rFVIIa protein was detected in minute amounts (ng/ml); however, this was not enough to prolong the dilute-TF time.


CONCLUSIONS
Local application of recombinant active-site inhibited human FVIIa reduced both thrombus weight and improved patency significantly in an experimental venous thrombosis model without affecting the systemic clotting times.
Holst
J
J
Dept. of Surgery, Helsingborg Hospital, Sweden.
Kristensen
A T
AT
Kristensen
H I
HI
Ezban
M
M
Hedner
U
U
D000768:Anesthesia, General; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D003251:Constriction, Pathologic / Q000150:complications; D004195:Disease Models, Animal; D004311:Double-Blind Method; D015942:Factor VIIa / Q000008:administration & dosage / Q000032:analysis / Q000037:antagonists & inhibitors*; D006801:Humans; D007275:Injections, Intravenous; D007601:Jugular Veins / Q000293:injuries; D010314:Partial Thromboplastin Time; D010919:Placebos; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins; D012039:Regional Blood Flow; D013925:Thromboplastin / Q000032:analysis; D013927:Thrombosis / Q000517:prevention & control*; D017539:Tunica Intima / Q000293:injuries; D014654:Vascular Patency / Q000187:drug effects*
D010919:Placebos; D011994:Recombinant Proteins; D013925:Thromboplastin; D015942:Factor VIIa