A COMPARISON BETWEEN FIBRINOLYSIS OF FRESH AND AGED CLOTS OR THROMBI BY rt-PA IN VIVO, EX VIVO AND IN VITRO
In view of the therapeutic applications of rt-PA it is of interest to investigate whether there is any difference in the lysability between fresh and aged thrombi. The efficiency of fibrinolysis by rt-PA was studied in 3 different ways: In vivo, by measuring the thrombus weight of fresh (1 h) or aged (24 h) thrombi in the carotid artery of rabbits which had been treated with rt-PA (0.4 mg/kg) or saline for 1 h. Ex vivo, by measuring I125-release of in vivo fresh (1 h) and aged (24 h) thrombi (labelled with I125-fibrinogen) suspended in vitro in plasma containing rt-PA (1 μg/ml) ; the thrombi were formed in the jugular vein and the carotid artery of each rabbit. In vitro, by measuring I125-release of fresh (1 h) and aged (6 or 24 h) human native whole blood clots, PPP-clots, PRP-clots and squeezed PPP-clots which were formed and lysed in vitro with rt-PA (1 μg/ml) . In vivo as well as ex vivo rt-PA lysed fresh (1 h) thrombi much better than aged (24 h) thrombi. This difference was more pronounced immediately after the onset of fibrinolysis, but decreased with time. However, in vitro relatively little difference was observed in fibrinolysis efficiency between fresh (1 h) and aged (6 or 24 h) clots; fibrinolysis of these clots was decreased (PPP > whole blood > PRP) with increasing clot retraction, which was almost complete within 1 h. This result was also confirmed when PPP-clots were “retracted” by simply squeezing them just before lysis. Therefore we conclude that a considerable difference in lysis efficiency between fresh and aged thrombi was only observed when thrombi were formed and aged in vivo. This difference was less pronounced with increasing fibrinolysis time.