797-4 Comparative Effects of Heparin, Aspirin, and Hirudin on Thrombus Growth on Fresh Mural Thrombus: Deaggregation of Mural Thrombus by Specific Thrombin Inhibition

Abstract

The presence of residual mural thrombus (MT) predisposes to recurrent thrombotic vessel occlusion. To compare the benefits of different antithrombotic and anti platelet agents we studied the growth of thrombus on a preexisting mural thrombus in a well characterized porcine perfusion system in which a fresh mural thrombus was formed by perfusing severely injured arterial wall with porcine blood for 5 min at a shear rate of 1690/s (corresponding to a moderate coronary stenosis). Thrombus formation was measured by morphometric analysis. The average mural thrombus achieved in 5 min was 0.135 mm 2 /mm (n = 17). To quantify the growth of thrombus, MT was perfused with whole blood of control and treated animals at the same flow conditions. Thrombus growth on MT was evaluated in pigs treated with Placebo, Aspirin (ASA, 5 mg/kg iv), Heparin IHep, 100 IU/kg/h) plus ASA iv, high-dose Hep (250 IU/kg/h iv), and r-Hirudin (1 mg/kg/h iv) as a probe for thrombin. Anticoagulation was evaluated by aPIT (sec). Results expressed as thrombus area (TA mm 2 /mm, ± SEM) and % growth of thrombus (GT) on MT were compared by Anova: Placebo ASA Hep + ASA Hep 250 r-Hir n 28 13 6 14 13 TA 0.29 ± 0.01 0.28 ± 0.02 0.20 ± 0.02 * 0.15 ± 001 * 007 ± 0.01 * , # , † %GT +119 ± 14 +110± 11 +48 ± 12 * +13 ± 5 * -48 ± 2 * , # , † apTT 31 ± 3 32 ± 5 46 ± 2 >300 68 ± 3 p < 0.05: * vs Placebo # vs hep250 † vs MT These data suggest that by directly inhibiting thrombin activity, r-hirudin completely inhibits growth of thrombus and is more effective al lower levels of anticoagulation than the highest does of heparin. Specific thrombin inhibition also leads to an overall reduction of the mural thrombus at shear rates typical of a moderate coronary stenosis indicating deaggregation of a pre-existing mural thrombus.