Thrombolytic Properties Of Purified Human Tissue Plasminogen Activator In A Dog Femoral Vein Thrombosis Model

1981 ◽  
Author(s):  
C Korninger ◽  
O Matsuo ◽  
R Suy ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Human Tissue ◽  
Femoral Vein ◽  
Culture Fluid ◽  
Control Group ◽  
Bleeding Tendency ◽  
Human Fibrinogen ◽  
Thrombosis Model ◽  
Tissue Plasminogen

Experimental thrombosis was produced in an isolated 4 cm section of the femoral vein in the groin region of beagle dogs using a mixture of 125I-labeled human fibrinogen (6 × 106 cpm), dog blood, thromboplastin and thrombin. Saline, 1,000,000 IU of urokinase or 100,000 Units (1 mg) of highly purified tissue plasminogen activator (isolated from the culture fluid of human melanoma cells) was infused intravenously over four hours. The extent of thrombolysis was calculated from the difference between the radioactivity introduced in the clot and that in the recovered clot six hours after the start of the infusion.In four control animals thrombolysis was 31.0 ± 3.0% (mean ± S.D.). Infusion of urokinase in 3 dogs resulted in 42.7 ± 14.3% lysis. In 5 dogs receiving plasminogen activator thrombolysis was 65.6 ± 21.6%. During infusion the blood radioactivity rose significantly (from 2.5 to 6.6% of the total) in the tissue plasminogen activator group; only a slight rise was observed in the urokinase group and a progressive decline in the control group.Neither in the controls nor in the tissue plasminogen activator treated animals significant activation of plasminogen, consumption of α-antiplasmin or fibrinogen breakdown occurred and no major bleeding was noted. Infusion of urokinase, however, resulted in systemic activation of the fibrinolytic system with extensive fibrinogen breakdown causing a significant bleeding tendency.It is concluded that in the experimental model used human tissue plasminogen activator has higher specific thrombolytic and a lower systemic fibrinogenolytic effect than urokinase.

Comparison of the Relative Fibrinogenolytic, Fibrinolytic and Thrombolytic Properties of Tissue Plasminogen Activator and Urokinase in Vitro

1981 ◽  
Vol 45 (03) ◽  
pp. 225-229 ◽  
Author(s):  
O Matsuo ◽  
D C Rijken ◽  
D Collen
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Human Tissue ◽  
Thrombolytic Agent ◽  
Blood Clot ◽  
Culture Fluid ◽  
Fibrinolytic System ◽  
Tissue Plasminogen

SummaryThe relative fibrinogenolytic, fibrinolytic and thrombolytic properties of human tissue plasminogen activator and human urokinase were compared in purified systems, in whole human plasma and in a system composed of a radioactive human blood clot (<sup>125</sup>I-fibrinogen) hanging in circulating human plasma. The human tissue plasminogen activator was highly purified from the culture fluid of a human melanoma cell line.In purified systems composed of fibrinogen or fibrin, plasminogen and α<sub>2</sub>-antiplasmin as well as in whole plasma, tissue plasminogen activator digested fibrin without degrading fibrinogen significantly. Urokinase did not have this specific fibrinolytic effect.In the circulating plasma system, the degree of fibrinolysis was proportional to the amount of activator added, tissue plasminogen activator being about 10 times more efficient than urokinase. In addition, tissue plasminogen activator appeared to cause negligible fibrinogen degradation. Tissue plasminogen activator still induced significant thrombolysis at a concentration of 10 IU per ml whereas no effect of urokinase was observed at 20 IU per ml. Infusion of 100 IU (1 (μg) of tissue plasminogen activator per ml resulted in moderate activation of the fibrinolytic system as judged from a decrease of plasminogen and α<sub>2</sub>-antiplasmin to 40-50 percent. Nevertheless, extensive fibrinolysis (50 to 80 percent of radioactivity released after 12 hrs) and only very limited fibrinogenolysis were observed. An equivalent amount of urokinase (100 IU per ml) only induced approximately 15 percent lysis in 12 hrs. At higher concentrations of urokinase (260 IU per ml or more) extensive activation of the fibrinolytic system was obtained as evidenced by a depletion of plasminogen, α<sub>2</sub>-antiplasmin and fibrinogen. This was associated with extensive fibrinolysis (approximately 60 percent after 12 hrs). It is concluded that human tissue plasminogen activator is a more specific and effective fibrinolytic-thrombolytic agent than human urokinase.

Inhibition Of Human Tissue Plasminogen Activator By Human Plasma : No Evidence For A Specific Antiactivator

1981 ◽  
Author(s):  
C Korninger ◽  
D Collen
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Rate Constant ◽  
Human Tissue ◽  
Gel Filtration ◽  
Culture Fluid ◽  
Α2 Macroglobulin ◽  
Tissue Plasminogen ◽  
The One

Human tissue plasminogen activator (TPA) was highly purified (one-chain or two-chain form) from the culture fluid of a melanoma cell line and labeled with 125 Gel filtration of mixtures of human plasma with trace amounts of labeled and 10 to 1,000 units/ml of unlabeled TPA revealed formation of two radioactive complexes with apparent Mr of 150,000 and 800,000, which were devoid of lytic activity of fibrin plates. These radioactive complexes were precipitated (90 and 63 percent) by antisera against α2 antiplasmin (α2AP) and α2-macroglobulin (α2M) respectively, but not by antisera against other known plasma protease inhibitors. In plasma specifically depleted in α2AP formation of the complex with Mr ≃ 150,000 did not occur, whereas removal of α2M abolished formation of the complex with Mr ≃ 800,000. The initial rates of formation of these two complexes in plasma were very similar to those obtained with mixtures of TPA and 1 μM α2AP or 3.5 μM α2M respectively. Complex formation was completely abolished by blocking the active site serine of TPA.In purified systems TPA was inhibited by α2AP with a rate constant of 140 M-1s-1 and by α2M with a rate constant of 30 M-1s-1. These rate constants correlate well with the rate of formation in plasma of the Mr ≃ 150,000 complex and the Mr ≃ 800,000 complex respectively.All these data indicate that TPA is slowly inhibited in human plasma by α2AP (tl/2 ≃ 60') and by α2M (tl/2 ≃ 120'). We found no evidence for the existence of another significant inhibitor in plasma. Both the one-chain and two-chain forms of TPA behaved very similarly in all experiments.

Abstract WP336: Impact of Anti-Hypertensive Interventions for Treatment of Acute Ischemic Stroke in Patients Receiving Tissue Plasminogen Activator

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jeffrey Leya ◽  
Elisabeth Donahey ◽  
Megan Rech
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Primary Endpoint ◽  
Univariate Analysis ◽  
Control Group ◽  
Poor Outcome ◽  
Tissue Plasminogen

Introduction: Early treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset is associated with neurologic improvement. A risk of rtPA is hemorrhagic conversion, which has a higher incidence in patients with elevated blood pressure at presentation. Current literature supports the use of blood pressure goals (<185/110 mm Hg) in patients qualifying for rtPA, but the effects of anti-hypertensive (anti-HTN) medications within the first 24 hours of AIS on outcomes has not been evaluated. Hypothesis: AIS patients requiring anti-HTN medications (anti-HTN group) before rtPA have a poorer outcome at 90 days compared to those that do not need anti-HTN medications (control group). Methods: This was a retrospective cohort study of patients >18 years diagnosed with AIS from January 2011 through December 2015 who received one or multiple anti-HTN medication(s) prior to rtPA administration, compared to control patients who did not. Primary endpoint was poor outcome at 90 days, defined as a modified Rankin Scale (mRS) of ≥3. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Multivariate analysis was conducted. Results: Of 235 patients evaluated for AIS, 145 (61.7%) were included. Baseline demographics were well matched, though more patients in the anti-HTN group had a history of HTN (86.7% vs. 62.5%, p<0.01), diabetes (33.3% vs. 17.5%, p=0.04) and chronic kidney disease (20% vs. 7.5%, p=0.04). There was no difference in the primary endpoint of poor outcome (mRS ≥3) between groups who received blood pressure medication versus those who did not (37% anti-HTN group vs. 30% control, p=.374). There was no difference in hemorrhagic conversion (13.3% anti-HTN group vs. 6.3% control, p=.187). Mortality at 90 days did not differ between groups (11% who received anti-HTN vs. 7.5%, p=.508). Conclusion: No difference was observed in poor outcomes, hemorrhagic conversion, or 90-day mortality in patients receiving anti-HTN medications prior to rtPA compared to those that did not. These results suggest that aggressive blood pressure management should be used to control hypertension in AIS who may qualify for rtPA, though larger, randomized trials are needed to confirm this finding.

Abstract 168: Outcomes of Intra-Arterial Tissue Plasminogen Activator Rescue Therapy During Stroke Thrombectomy-Insights From the STAR Collaboration

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eyad Almallouhi ◽  
Sami Al kasab ◽  
Ali Alawieh ◽  
Reda M Chalhoub ◽  
Mohammad Anadani ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Functional Outcomes ◽  
Mechanical Thrombectomy ◽  
Rescue Therapy ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Arterial Tissue ◽  
Tissue Plasminogen

Introduction: Intra-arterial tissue plasminogen activator (IA-tPA) can be used as rescue therapy during mechanical thrombectomy for stroke patients, mostly in the setting of distal occlusion. The outcomes of IA-tPA has not been assessed in large-scale multi-center studies yet. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which included prospectively maintained databases of 11 thrombectomy-capable stroke centers in the US, Europe, and Asia. We compared the baseline characteristics, procedural metrics, rate of symptomatic intracranial hemorrhage (sICH), and long-term functional outcomes between thrombectomy patients who received rescue IA-tPA and a control group of thrombectomy patients with matched age, National Institute of Health stroke scale (NIHSS) on presentation, location of occlusion and IV-tPA receipt. Results: A total of 2827 thrombectomy patients were included in the STAR registry. Out of those, 205 patients received IA-tPA. We matched 191 patients from the IA-tPA group with a control group of 191 patients (table 1). No difference was seen in age, sex, race, vascular risk factors, or Alberta Stroke Program Early CT (ASPECT) score between both groups. In addition, procedural metrics, including onset to groin time, the procedure duration, and rate of successful recanalization (modified Thrombolysis in Cerebral Infarction score≥2b) were similar. Finally, similar outcomes were noted in both groups, including the rate of sICH and good 90-day functional outcome (modified Rankin scale≤2). Conclusion: The use of IA-tPA as an adjunctive treatment to mechanical thrombectomy was safe but did not result in a higher rate of successful recanalization or good long-term functional outcomes.

Cloning and Expression of a Human Tissue Plasminogen Activator Variant:K2S in Escherichia coli

2007 ◽  
Vol 10 (6) ◽  
pp. 946-949 ◽  
Author(s):  
Hamid Mir Mohammad S ◽  
Kianoush Dormiani ◽  
Yahya Khazaie ◽  
Mohammad Rabbani ◽  
Fatemeh Moazen
Keyword(s):  
Escherichia Coli ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Human Tissue ◽  
Cloning And Expression ◽  
Tissue Plasminogen
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