Coronary thrombolysis with K1K2PU, a chimeric tissue-type and urokinase-type plasminogen activator

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Abstract
Background: K1K2PU is a recombinant chimeric tissue-type and urokinase-type plasminogen activator consisting of the two kringle domains (K, and K2) of human tissue-type plasminogen activator (t-PA) and the serine proteinase domain (Pu) of single-chain urokinase-type plasminogen activator (scu-PA). In experimental animal models of thrombosis, its thrombolytic potency has been shown to be five- to 10-fold greater than that of its parent molecules. Methods: The effect of a bolus injection of K1K2Pu on coronary thrombolysis over 30 min was evaluated in six patients with acute myocardial infarction of less than 5 h duration in whom total occlusion of the infarct-related artery was confirmed using angiography. Results: In two patients given an intravenous bolus of 10mg over 5 min, persistent coronary artery recanalization was not observed within 30 min. In two out of four patients given a second bolus of 10mg K1K2Pu, 15 min after the first, persistent coronary recanalization occurred within 30 min. The four patients without recanalization within 30 min were immediately given 100 mg t-PA over 90 min. In all patients the infarct-related artery was patent after 24 h, and the hospital course was uneventful. The bolus injections did not produce significant fibrinogen breakdown or α2-antiplasmin consumption within 30 min. The plasma K1K2Pu level increased to 2–3μg/ml after the first bolus injection and to 4–5μg/ml after the second. K1K2PU disappeared from the plasma with an initial half-life of 9 min and a clearance of approximately 50ml/min. Conclusion: A bolus injection of 20 mg K1K2PU is well tolerated and can induce clot-selective coronary thrombolysis in patients with acute myocardial infarction.

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