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Acute coronary syndromes
Published in Henry J. Woodford, Essential Geriatrics, 2022
If fibrinolysis is the better option, then this should be given within ten minutes of diagnosis, which can be pre-hospital. Contraindications to thrombolysis include prior intracerebral haemorrhage (ICH), ischaemic stroke in the last six months or a gastrointestinal bleed in the last month. A half-dose of tenecteplase should be considered for people aged over 75 due to lower risk of ICH.12 Anticoagulation and transfer to a PCI centre are often recommended following fibrinolysis. Early angiography (within 24 hours) or rescue PCI can be considered if there is no evidence of cardiac reperfusion (i.e. ST-segment resolution < 50% or clinical deterioration). Aspirin and clopidogrel are usually started around the same time.12
Pulmonary Embolism
Published in Stephen M. Cohn, Alan Lisbon, Stephen Heard, 50 Landmark Papers, 2021
Jennifer Lynde, Ana M. Velez-Rosborough, Enrique Ginzburg
For submassive high risk to massive PE, anticoagulation in addition to thrombolysis or thrombectomy may be indicated. Patients that have normal systolic blood pressure but show signs of right ventricular dysfunction may benefit from thrombolysis to avoid hemodynamic decompensation (Goldhaber). Thrombolytic agents such as Tenecteplase can provide rapid resolution of emboli. However, prior to fibrinolysis, patients must undergo extensive bleeding risk assessment as use of thrombolytics has significant bleeding complications. The PEITHO trial demonstrated great efficacy at preventing hemodynamic compromise but does increase the risk of intracranial hemorrhage and major bleeding events, especially for patients over the age of 75. There is some thought that half the standard dose of Tenecteplase may decrease bleeding risks; however, more research is needed (Meyer). For massive PE or patients that require aggressive intervention for PE but are at high risk for bleeding should be considered for catheter or surgical thrombectomy. Catheter-directed thrombolysis (CDT) has shown to be effective with low bleeding risks. However, randomized controlled trials are needed to compare directly with anticoagulation or systemic thrombolytics (Bloomer). In short, treatment beyond anticoagulation requires a thorough bleeding risk assessment and discussion with the patient regarding the risks and benefits of each procedure.
Haemostasis: Normal Physiology, Disorders of Haemostasis and Thrombosis
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Elizabeth Jones, Russell David Keenan
Fibrinolytic agents (i.e. streptokinase, tenecteplase, urokinas) all act by promoting plasmin indirectly and thus mediating clot breakdown. They are short acting and all potentially give a high bleeding risk. They are most commonly used in the acute management of stroke and myocardial infarction. In the event of serious bleeding, use of tranexamic acid and FFP or fibrinogen concentrates is indicated with other treatment guided by coagulation tests.
Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy: a narrative review
Published in Expert Opinion on Pharmacotherapy, 2023
Muath Alobaida, Gregory Y H Lip, Deirdre A Lane, Dimitrios Sagris, Andrew Hill, Stephanie L Harrison
Although, alteplase remains the standard-of-care in IVT, tenecteplase may be a safe and effective alternative in patients undergoing both IVT and EVT[13]. One small randomized controlled trial including 202 patients with anterior and basilar ischemic stroke eligible for EVT showed higher recanalization rate, borderline association with better functional outcomes, and similar proportions of sICH in patient treated tenecteplase compared to alteplase[19]. Further, pooled subgroup analysis of two randomized controlled trials demonstrated higher rates of recanalization and functional outcomes in patient treated with tenecteplase compared to alteplase[20]. Accordingly, a meta-analysis of post-hoc pooled subgroup analysis of randomized controlled trials based on non-clinical primary outcomes showed better functional outcomes (modified Rankin Scale; mRS, 0–2) with tenecteplase compared to alteplase (OR: 2.09, 95% CI: 1.16–3.76)[13].
Mechanical thrombectomy – is time still brain? The DAWN of a new era
Published in British Journal of Neurosurgery, 2018
Naveed Kamal, Neil Majmundar, Nitesh Damadora, Mohammad El-Ghanem, Rolla Nuoman, Irwin A. Keller, Steven Schonfeld, Igor Rybinnik, Gaurav Gupta, Sudipta Roychowdry, Fawaz Al-Mufti
Research in stroke has been reinvigorated, more so after the findings of the 5 landmark trials and the DAWN trial. The only approved intravenous thrombolytic in the US is alteplase, and its use is limited to the 3 hour time window. However, due to its limited efficacy in reperfusing large vessels and its short half-life, other thrombolytic agents have been investigated. Tenecteplase is a potential therapy for acute ischemic stroke, particularly because it is 15 times more specific for fibrin and has a longer half-life.59 This could lead to a reduced need to maintain an infusion of thrombolytics after the initial bolus. In addition, it is more resistant to plasminogen activator inhibition.60 This has led to its adoption as the preferred thrombolytic in acute ST-elevation myocardial infarction.61 A study by Parsons et al. found that tenecteplase given at a dose of .25 mg/kg was superior to alteplase in reperfusion and clinical outcomes.62 In addition, the NOR-TEST investigators announced that tenecteplase was associated with functional outcomes and safety similar to alteplase. Currently, several multicenter RCTs are underway comparing tenecteplase to alteplase (TEMPO-2, TIAS, TASTE, and EXTEND IA TNK).63
Improving fibrinolysis in venous thromboembolism: impact of fibrin structure
Published in Expert Review of Hematology, 2019
Different variants of alteplase have been developed subsequently with the aim of increasing the fibrin-specificity of the agent and decreasing the plasma clearance of the molecule so that the agent could be given as a bolus. Reteplase and desmoteplase have been compared with rtPA in acute PE, showing no improvement in hemodynamic parameters [89]. Tenecteplase, developed by Genentech Inc., is the most successful alteplase variant that is given as a single bolus and is more fibrin-specific than alteplase, which is associated with a lower risk of non-intracranial bleedings (tenecteplase < alteplase < streptokinase) [90]. Tenecteplase that was evaluated in patients with intermediate-risk PE has the efficacy similar to rtPA [91]. None of these agents is approved for use in PE.