Summary
Recombinant tick anticoagulant peptide (r-TAP) is a potent and specific inhibitor
of activated coagulation factor X which effectively interrupts in vivo arterial thrombosis
during treatment. It is, however, uncertain if it also affects thrombosis after treatment
is stopped. This was tested in a baboon model of arterial thrombosis where platelet
deposition onto Dacron vascular graft segments, inserted as extensions into permanent
femoral arteriovenous shunts, was measured. The baboons were intravenously treated
with 10 μg/kg/min (low dose, aPTT = 39 ± 1 s) and 25 μg/kg/min (high dose, aPTT =
58 ± 2 s) r-TAP for two hours. During treatment the r-TAP inhibited thrombin formation
and dose-dependently interrupted platelet deposition onto the graft segment. This
effect lasted for up to two hours after treatment with the low dose. Following treatment
with the high dose, the graft segments were kept in place for 53 h. After treatment
was stopped, platelets again deposited, but at a much lower rate than in control studies.
Maximum deposition was approximately 38% lower than in the control studies. Total
platelet deposition over 55 h, calculated as the area under the deposition curve,
was approximately 40% (p <0.05) less than in the control studies. A significant shortening
in the mean platelet life span and an approximately 15-fold increase in thrombin-antithrombin
III complexes during the first 31 h indicated that the thrombus surface remained thrombogenic
and that the effect of r-TAP was transient. We have shown that 2 h of treatment with
a full antithrombotic dose of r-TAP markedly reduced both the rate of platelet deposition
after treatment was stopped and the total number of platelets deposited over 55 h.
This was in spite of the finding that the antithrombotic effect of r-TAP was transient.
