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Urokinase, also known as urinary-type plasminogen activator (uPA), is found in urine. Clinically, UK is used as a thrombolytic drug in conditions such as pulmonary embolism, myocardial infarction, and severe deep venous thrombosis (DVT). In comparison to rtPA, SK and UK lack fibrin specificity and bind equally to circulating plasminogen and clot-bound plasminogen. On binding with plasminogen, SK forms a complex that activates plasmin, triggering a proteolytic cascade. The proteolytic cascade leads to thrombolysis (clot degradation in AIS) or extracellular matrix degradation (e.g., tissue degradation causing tissue invasion and metastasis in tumour malignancy) depending upon the physiological environment. Therefore, SK and UK have less favourable adverse event profiles than rtPA. Thrombolytic drugs can be used as (a) Intravenous, and (b) Intra-arterial. Next, we will discuss the important aspects of these thrombolytic procedures.
The idea behind combining intravenous and endovascular approaches, also called bridge therapy [136,137,138,139,140,141] or multimodal reperfusion therapy (MMRT), is to take advantage of best of both approaches by allowing fast and early access to IV-rtPA within the first 4.5 h of stroke onset, and superior recanalization rates even for delayed time windows beyond 4.5 h using endovascular therapy . Notably, the Interventional Management of Stroke (IMS) I  and II  trials were conducted to investigate the feasibility and safety of combined interventions: low dose, 0.6 mg/kg, IV-rtPA followed by intra-arterial rtPA within 3 h since stroke onset, to recanalization of AIS. The bridge IV and IA therapy were not significantly different from the IV-rtPA alone as both yielded similar proportions of ICH, rates of mortality and mRS at 90 days. The subsequent IMS III trial also found no additional benefit of bridge therapy compared with IV-rtPA alone . One of the important factors that may have played a role in these results is the time delay (approximately 32 min) between the IV-rtPA and initiation of intra-arterial therapy [121, 143]. Unlike the neutral results of IMS III trial, a recent meta-analysis reported a significantly strong association of combined intravenous-IA thrombolysis over IV fibrinolysis alone with favourable outcome, reduced mortality, and improved recanalization rates .
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