TY - JOUR

T1 - Local application of recombinant active-site inhibited human clotting factor VIIa reduces thrombus weight and improves patency in a rabbit venous thrombosis model

AU - Holst, J.

AU - Kristensen, A. T.

AU - Kristensen, H. I.

AU - Ezban, M.

AU - Hedner, U.

PY - 1998

Y1 - 1998

N2 - 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 systematic changes in the coagulation. Design: Experimental double-dummy randomised study. Materials: In 20 healthy New Zealand White rabbits both juguIar 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 systematic clotting times.

AB - 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 systematic changes in the coagulation. Design: Experimental double-dummy randomised study. Materials: In 20 healthy New Zealand White rabbits both juguIar 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 systematic clotting times.

KW - FVIIa

KW - Inactivated FVIIa

KW - Patency

KW - TF

KW - TF-FVII-dependent coagulation

KW - Venous thrombosis

UR - http://www.scopus.com/inward/record.url?scp=0031876354&partnerID=8YFLogxK

U2 - 10.1016/S1078-5884(98)80112-3

DO - 10.1016/S1078-5884(98)80112-3

M3 - Journal article

C2 - 9659887

AN - SCOPUS:0031876354

VL - 15

SP - 515

EP - 520

JO - European Journal of Vascular and Endovascular Surgery

JF - European Journal of Vascular and Endovascular Surgery

SN - 1078-5884

IS - 6

ER -