• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.6-12
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• 2009

Background: The efficacy of several thrombolytic agents for treating massive pulmonary thromboembolism (PTE) has been reported to be similar. However, the difference of the bleeding complications caused by two commonly used thrombolytic agents in PTE patients is not well known. The aim of this study was to compare the therapeutic efficacy and the bleeding complications between urokinase and recombinant tissue-type plasminogen activatior (rt-PA, alteplase) in a Korean medical center. Methods: We retrospectively reviewed the clinical data of the patients who were treated with thrombolytic agents (urokinase and alteplase) because of massive PTE. Results: A total of 40 patients were included: 16 (40%) treated with urokinase and 24 (60%) with alteplase. The patients treated with alteplase showed a shorter duration of using vasopressor agents than did the patients who were given urokinase, but the duration of mechanical ventilation, the length of the ICU stay and the hospital stay were not different between the thrombolytic agents. Five patients treated with urokinase and eight patients treated with alteplase died (p=0.565): One patient in the urokinase group and four patients in the alteplase group died due to pulmonary thromboembolism. Bleeding complications after thrombolysis were observed in 3 patients (7.5%) treated with urokinase and in 11 (27.5%) patients treated with alteplase (p=0.079). Major bleeding complication occurred in 2 patients who were treated with alteplase. Conclusion: Urokinase seems to have fewer bleeding complications with an equivalent efficacy, as compared to alteplase, in Korean patients who suffer with massive pulmonary thromboembolism.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• Tuberculosis and Respiratory Diseases
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• v.87 no.3
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• pp.378-385
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• 2024

Background: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. Methods: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. Results: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean±standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. Conclusion: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

• BMB Reports
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• v.44 no.1
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• pp.34-39
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• 2011

Resistance to PAI-1 is a factor which confers clinical benefits in thrombolytic therapy. The only US FDA approved PAI-1 resistant drug is Tenecteplase$^{(R)}$. Deletion variants of t-PA have the advantage of fewer disulfide bonds in addition to higher plasma half lives. A new variant was developed by deletion of the first three domains in t-PA in addition to substitution of KHRR 128-131 amino acids with AAAA in truncated t-PA. The specific activity of this new variant, $570\;IU/{\mu}g$, was found to be similar to those found in full length t-PA (Alteplase$^{(R)}$), $580\;IU/{\mu}g$. A 65% and 85% residual activity after inhibition by rPAI-1 was observed for full length and truncated-mutant form, respectively. This new variant as the first PAI-1 resistant truncated t-PA may offer more advantages in clinical conditions in which high PAI-1 levels makes the thrombolytic system prone to re-occlusion.