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  • Title: Local application of recombinant active-site inhibited human clotting factor VIIa reduces thrombus weight and improves patency in a rabbit venous thrombosis model.
    Author: Holst J, Kristensen AT, Kristensen HI, Ezban M, Hedner U.
    Journal: Eur J Vasc Endovasc Surg; 1998 Jun; 15(6):515-20. PubMed ID: 9659887.
    Abstract:
    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. DESIGN: Experimental double-dummy randomised study. MATERIALS: 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.
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