Comparison of Plasmin With Recombinant Tissue-Type Plasminogen Activator in Lysis of Cerebral Thromboemboli Retrieved From Patients With Acute Ischemic Stroke

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Abstract
Plasmin is a direct-acting thrombolytic with a better safety profile than recombinant tissue-type plasminogen activator (rtPA) in animal models. With the application of retrieval devices for managing acute ischemic stroke, extracted thromboemboli are available for ex vivo examination. We ask whether such thrombi are amenable to plasmin thrombolysis and whether such activity is different with rtPA. Thromboembolic fragments (total 29) were retrieved from the intracranial carotid artery system of 15 patients with acute ischemic stroke and randomly assigned to ex vivo thrombolysis with plasmin or rtPA. After an initial 2-hour exposure, residual material was exposed to the other agent for an additional 2 hours. Thrombolysis was quantified by change in thrombus area and released d -dimer. Plasmin induced significant ex vivo thrombolysis of cerebral arterial thromboemboli, decreasing area by 45.9%±29.4% and 69.2%±52.5% and inducing median d -dimer release of 108 180 μg/L (range, 16 780 to 668 050 μg/L) and 16 905 μg/L (range, 240 to 403 085 μg/L) during the first and second 2-hour incubation periods, respectively. These changes were not different from those obtained with rtPA, which decreased area by 34.7%±57.8% ( P =0.63) and by 68.4%±26.9% ( P =0.97) and induced median d -dimer release of 151 990 μg/L (range, 9870 to 338 350 μg/L; P =0.51) and 34 520 μg/L (range 3794 to 325 400 μg/L; P =0.19) during the first and second 2-hour incubations. Retrieved human cerebral thromboemboli were amenable to ex vivo lysis by plasmin, the rate and degree of which was not different than that achieved with rtPA.

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