Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: The Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy

Serebruany, Victor L.; Malinin, Alex I.; Callahan, Kevin P.; Binbrek, Azan S.; Werf, Frans Van de; Alexander, John H.; Granger, Christopher B.; Gurbel, Paul A.

doi:10.1067/mhj.2003.210

Cited by 33 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This underscores the importance of delivery of this compound in scenarios where stroke patients are unable to receive treatment under the current stipulated 3-hour time limit. Efficacy of TNK-tPA has also been demonstrated in various clinical trials and has shown reduced mortality among patients receiving late treatment and decreased incidence of noncerebral hemorrhages (Armstrong et al, 2003;Van de Werf et al, 2001;Serebruany et al, 2003).…”

Section: The Role Of New Thrombolytic Agentsmentioning

confidence: 99%

The Neurotoxicity of Tissue Plasminogen Activator?

Kaur

Zhao

Klein

et al. 2004

J Cereb Blood Flow Metab

240

185

View full text Add to dashboard Cite

Abstract:Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. Besides clot lysis per se, tPA may have pleiotropic actions in the brain, including direct vasoactivity, cleaveage of the N-methyl-Daspartate (NMDA) NR1 subunit, amplification of intracellular Ca ++ conductance, and activation of other extracellular proteases from the matrix metalloproteinase (MMP) family, e.g. MMP-9. These effects may increase excitotoxicity, further damage the BBB, and worsen edema and cerebral hemorrhage. If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain. Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed.

show abstract

Section: The Role Of New Thrombolytic Agentsmentioning

confidence: 99%

The Neurotoxicity of Tissue Plasminogen Activator?

Kaur

Zhao

Klein

et al. 2004

J Cereb Blood Flow Metab

240

185

View full text Add to dashboard Cite

show abstract

“…More specifically, tenecteplase is a genetically engineered plasminogen activator with reduced risk for causing major bleeds due to restricted lytic activity to the plasmin on the fibrin surface that avoids the breakdown of fibrinogen, factor V, factor VIII and a2-antiplasmin [22]. Compared to other thrombolytic regimens, tenecteplase is not affected by other drugs such as nitrates, it has more robust anti-platelet effects and exerts higher thrombolytic potency even when given more than 4 hours after the onset of symptoms [9,21,23]. More than 25000 patients have been so far recruited in clinical trials that used tenecteplase as a potential therapeutic regimen making the use of this drug evidence based.…”

Section: Discussionmentioning

confidence: 99%

“…The first clinical trials, ASSENT2 [9] and ASSENT3 [10] proved tenecteplase equally safe and efficient to alteplase, while the latest clinical trial highlighted its role in comparison to PCI [8,11].…”

Section: Introductionmentioning

confidence: 99%

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Tseliou¹,

Ntalianis²,

Diakos³

et al. 2016

J Transl Sci

View full text Add to dashboard Cite

Thrombolysis remains the treatment of choice in patients who are far from the catheterization laboratories. Although full dose is advisable low dose has not been preclinically tested. Here we tested the hypothesis that low dose tenecteplase, a recombinant fibrin-specific plasminogen activator can induce efficient thrombolysis even in lower doses than the hitherto indicated, compared to full-dose thrombolytic therapy for ST-segment myocardial infarction. Farm pigs (30-35 kg, n=23) were imposed in a clinically relevant model of thrombosis. We used both the common carotid arteries (CA) and the left anterior descending artery (LAD) below the first diagonal. The vessels were initially externally injured (application of pressure by forceps) followed by an appropriate for the vessel dose of thrombin (100 IU for the LAD and 190 IU for CA). Occluding thrombi was achieved in 80% for the LAD and 57% for the CA. Ten minutes post occlusion the animals were allocated under continuous electrocardiogram and ultrasonic flow meter monitoring to one of the following groups: Group A) half-dose tenecteplase (2000 IU); Group B) Full dose tenecteplase (5000 IU); Group C) saline only. All animals received 60IU heparin and antiplatelet agents. The follow-up was 120 minutes post therapy administration. Sixty minutes after lytic drug administration recanalization occurred in 58% of the occluded arteries in Group A, in 85% in Group B and in 20% in Group C (P=0.028). Both tenecteplase regimens were effective for treating carotid artery thrombosis (71% Group A vs. 75% in Group B vs. 33% in Group C, P=0.286), but low dose was significantly less effective in reestablishing flow in proximally occluded LADs (25 % in Group A vs. 100% in Group B vs. 0% in Group C, P=0.015). All vessels with restored flow at 60 minutes remained patent at least for 1 hr. In Group A, at 60 minutes after tenecteplase administration, flow velocity in LAD reached 30% of the baseline value and 45% in carotids, while in Group B flow was 160% and 55% respectively, suggesting restoration of larger lumen diameter in the treated vessels. Post reperfusion ventricular arrhythmias that required treatment occurred equally in all groups. No differences in hemodynamic tested parameters were observed between the groups. In conclusion, we developed a clinically relevant model useful for testing the efficacy of different thrombolytic regimens. Our data demonstrate that low dose tenecteplase can be successfully used for treating thrombosis of larger diameter vessels, such as the carotids, but appears inadequate for treating LAD thrombotic occlusions.

show abstract

“…3). The current localization of the MA-33B8 epitope is distinct from the proposed vitronectin binding site (residues 55,101,105,109,110,120,122,123,136,138,139) [186][187][188], which is in agreement with the previously made observation that this ligand does not interfere with the MA-33B8/PAI-1 interaction [175]. Recently, the determination of the threedimensional structure of the somatomedin B/PAI-1 complex confirmed that somatomedin B (the bindingsite for PAI-1 on vitronectin) binds across the E and F helices of PAI-1 [189].…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

“…Large clinical trials have demonstrated equivalence in the mortality and intracranial hemorrhage between TNKase® and alteplase. However, it was also shown that TNKase® leads to lower rates of bleeding complications especially among high-risk patients [116][117][118][119][120].…”

Section: Pai-1 and Cardiovascular Diseasementioning

confidence: 99%

Plasminogen Activator Inhibitor-1

Gils¹,

Declerck

2004

CMC

View full text Add to dashboard Cite

Plasminogen activator inhibitor-1 (PAI-1) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type and urokinase-type plasminogen activator. Consequently, PAI-1 plays an important role in cardiovascular diseases (mainly through inhibition of t-PA) and in cell migration and tumor development (mainly through inhibition of u-PA). As a member of the serpin superfamily, PAI-1 shares important structural properties with other serpins. However, PAI-1 also exhibits unique conformational and functional properties. The current paper provides an overview of the knowledge on PAI-1 gathered since its discovery two decades ago. We are discussing (a) its structural properties and their subsequent association with the functional properties, (b) its role in a wide variety of (patho)physiological processes and (c) a number of strategies to interfere with its functional properties eventually aiming at pharmacological modulation of this risk factor.

show abstract

Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: The Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy

Cited by 33 publications

References 36 publications

The Neurotoxicity of Tissue Plasminogen Activator?

The Neurotoxicity of Tissue Plasminogen Activator?

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Plasminogen Activator Inhibitor-1

Contact Info

Product

Resources

About