A faster-acting and more potent form of tissue plasminogen activator.

Keyt, B. A.; Paoni, Nicholas F.; Refino, CJ; Berleau, Lea T.; Nguyen, Hung Van; Chow, Alice M.; Lai, Juan; Peña, Luisa; Pater, Cheryl; Ogez, John R.

doi:10.1073/pnas.91.9.3670

Cited by 324 publications

(226 citation statements)

References 34 publications

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“…A newer type of rTPA called tenecteplase was designed to be more resistant to inhibition by PAI‐1 to overcome the high level of inhibition 22. This product has been used in a single horse in combination with a DNase with a successful outcome 23…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a tentative treatment protocol is proposed: consider administration of IPFT if the pleural effusion remains above the level of the drain or is trapped in fibrin loculations 24 h after the placement of indwelling chest drains. Tenecteplase could be used in preference to alteplase, based on better theoretical performance in septic effusions 22. If using alteplase, 2–10 mg per dose q12–24 h for 3 days, with a dwell‐time of approximately 4 h is a recommended treatment course.…”

Section: Discussionmentioning

confidence: 99%

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The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Tomlinson

Byrne

Pusterla

et al. 2015

Veterinary Internal Medicne

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BackgroundInformation about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited.Hypothesis/ObjectivesDescribe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally.AnimalsHorses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally.MethodsRetrospective multicenter case series from 2007–2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes.ResultsThirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375–20,000 μg/hemithorax) was administered 1–4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow‐up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge.Conclusions and clinical importanceTreatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Tomlinson

Byrne

Pusterla

et al. 2015

Veterinary Internal Medicne

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“…A TNK-tPA dosage of 0.53 m a g was selected as the most appropriate for the ASSENT-2 trial!. l 6 ASSENT-2 was a Phase 111 trial that randomized 16,949 patients with AM1 and ST-segment elevation presenting within 6 h to a weight-optimized TNK-tPA regimen or t-PA.I7. Ix The study was designed to demonstrate equivalence between the drugs.…”

Section: Assent-2: An Equivalence Trialmentioning

confidence: 99%

Issues in the assessment of the safety and efficacy of tenecteplase (TNK‐tPA)

Gibson

Marble

2001

Clinical Cardiology

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Summary:While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety ofalteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 Ib) without an increased risk of ICH or death. Furthermore, the results ofTNK-tPA clinical trials showed that even at the highest weight-optimized dosage of50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.

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“…The molecule also possesses 14-fold enhanced fibrin specificity than t-PA but comparable fibrin-binding affinity and plasma clot lysis activity in vivo. 89 Clinical trials showed no difference between t-PA and TNK-tPA in reducing infarct mortality during AMI, however, there was a decrease in major bleeding rate in comparison with t-PA. 92 In the TIMI 10B (Thrombolysis in Myocardial Infarction) trial a single bolus administration of TNK-tPA (40 mg) produced the same patency rate at 90 min of thrombolytic therapy as the accelerated regimen of alteplase. 93 In the ASSENT-1 (Assessment of Safety and Efficacy of a New Thrombolytic agent) trial, a single bolus (30 to 50 mg) administration of tenecteplase was found to be as safe as the accelerated alteplase administration regimen in the treatment of patients with AMI.…”

Section: Third Generation Plasminogen Activatorsmentioning

confidence: 99%

“…5 (ii) Tenecteplase (TNK-tPA) It is a variant of t-PA with 3 point mutations {(i) Thr 103 with Asn, (ii) Asn 117 with Gln and (iii) Lys 296 -His 297 -Arg 298 -Arg 299 each replaced with alanine} and a molecular weight of 65 kDa (527 residues). 89 The first mutation at position 103 introduces a glycosylation site while the second mutation deletes the glycosylation site within the kringle 1 domain which also prolongs its half-life to about 10-24 min since it is partly responsible for t-PA elimination. 90 Owing to its slow clearance rate, a single bolus regimen can be administered simplifying its application outside of a hospital setting.…”

Section: Third Generation Plasminogen Activatorsmentioning

confidence: 99%

The evolution of recombinant thrombolytics: Current status and future directions

Adivitiya

Khasa

2016

Bioengineered

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Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

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A faster-acting and more potent form of tissue plasminogen activator.

Abstract: Current treatment with tissue painogen activator (tPA) requires an Intravenous infusion (1.5-3 h) became the clearance of tPA from the circulation is rapid (t1/2 6 min).

Cited by 324 publications

References 34 publications

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Issues in the assessment of the safety and efficacy of tenecteplase (TNK‐tPA)

The evolution of recombinant thrombolytics: Current status and future directions

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