Comparison of local thrombolytic efficacy of plasmin and rt-PA in an in-vitro flow system; a pilot study.

Plasmin, a directly acting thrombolytic agent, demonstrated a very favorable safety profile upon intra-arterial delivery to the clot site; however, its thrombolytic efficacy remains to be further assessed. In this study, differences in thrombolysis between clots exposed to equimolar concentrations of plasmin and recombinant tissue-type plasminogen activator (rt-PA) after partial vessel recanalization were tested in a model system. Model blood clots were prepared in glass chambers enabling direct observation by dynamic optical microscopy. The incubation of clots with plasmin (2.4mg/ml) or rt-PA (2.63mg/ml), allowing for the initial biochemical clot degradation, was followed by flushing' the clots with tangentially directed plasma flow devoid of a thrombolytic agent, mimicking blood flow after partial vessel recanalization. The acquired images were analyzed for nondissolved blood clot area as a function of time. With both thrombolytic agents, the relative clot area decreased rapidly in the first 30s after initiation of perfusion due to flushing' the degraded clot fragments (after plasmin by 0.26 +/- 0.22 and after rt-PA by 0.34 +/- 0.21, P=0.60). In the following minutes, the clot size showed a linear time dependence: after incubation with plasmin the clot size did not change substantially any more, whereas after incubation with rt-PA the clot size continually decreased. The slopes of the regression lines differed significantly (r(pl)=-8.9 10(-3) vs. r(rtPA)=-44.110(-3)/min, P<0.01). In conclusion, the thrombolytic action of plasmin was terminated rapidly by contact with flowing blood plasma, whereas the thrombolytic action of rt-PA was prolonged. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.