Tenecteplase in Acute Stroke: What About the Children?

Tenecteplase is replacing alteplase as the fibrinolytic agent of choice for the acute management of ischemic stroke in many adult stroke centers due to practical and pharmacokinetic advantages in the setting of similar outcomes. Although thrombolytic use is increasing for acute childhood stroke, there is very limited experience with tenecteplase in children for any indication, and importantly, there are no data on safety, dosing, or efficacy of tenecteplase for childhood stroke. Changes in fibrinolytic capacity over childhood, pediatric pharmacological considerations such as age-specific differences in drug clearance and volume of distribution, and practical aspects of drug delivery such as availability in children’s hospitals may impact decisions about transitioning from alteplase to tenecteplase for acute pediatric stroke treatment. Pediatric and adult neurologists should prepare institution-specific guidelines and organize prospective data collection.

[1]  Y. Liu,et al.  Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial , 2023, The Lancet.

[2]  R. Deng,et al.  Population Pharmacokinetics of Tenecteplase in Patients With Acute Myocardial Infarction and Application to Patients With Acute Ischemic Stroke , 2022, Journal of clinical pharmacology.

[3]  J. Latorre,et al.  Age-specific trends in intravenous thrombolysis and mechanical thrombectomy utilization in acute ischemic stroke in children under age 18 , 2022, International journal of stroke : official journal of the International Stroke Society.

[4]  Alexander M. Fraser,et al.  Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial , 2022, The Lancet.

[5]  S. Mayer,et al.  Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke , 2022, Stroke.

[6]  H. Samion,et al.  Role of tenecteplase (rtPA) to re‐establish flow in intraprocedural stent thrombosis in infants undergoing ductal stenting for duct‐dependent pulmonary circulation—a case series , 2021, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[7]  A. Ahmed,et al.  Unusual presentation of mitral prosthetic heart valve thrombosis managed with low dose tenecteplase infusion , 2021, Cardiology in the Young.

[8]  V. Afreixo,et al.  Tenecteplase for thrombolysis in stroke patients: Systematic review with meta-analysis. , 2020, The American journal of emergency medicine.

[9]  W. Powers,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. , 2019, Stroke.

[10]  T. Steiner,et al.  Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11–13 November 2018 , 2019, European stroke journal.

[11]  J. Assmus,et al.  Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial , 2017, The Lancet Neurology.

[12]  P. Noonan,et al.  1270: Tenecteplase Use in Children with Intravascular Thrombosis , 2013 .

[13]  M. Simpson,et al.  Simultaneous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults. , 2011, Thrombosis research.

[14]  Y. Lentz,et al.  In vitro stability and compatibility of tenecteplase in central venous access devices , 2011, Hemodialysis international. International Symposium on Home Hemodialysis.

[15]  R. J. Valentine,et al.  Device and Imaging-Specific Volumetric Analysis of Clot Lysis after Percutaneous Mechanical Thrombectomy for Iliofemoral DVT , 2010, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[16]  J. Grotta,et al.  Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial , 2010, Stroke.

[17]  R. Ichord,et al.  Thrombolysis in Acute Childhood Stroke: Design and Challenges of the Thrombolysis in Pediatric Stroke Clinical Trial , 2009, Neuroepidemiology.

[18]  K. Hagspiel,et al.  Ultrasound-accelerated thrombolysis for the treatment of deep vein thrombosis: initial clinical experience. , 2008, Journal of vascular and interventional radiology : JVIR.

[19]  Chad M. Davis,et al.  Aggressive percutaneous mechanical thrombectomy of deep venous thrombosis: early clinical results. , 2007, Archives of surgery.

[20]  P. Monagle,et al.  Fibrinolytic System in Adolescents: Response to Venous Occlusion Stress Tests , 2003, Pediatric Research.

[21]  E. Braunwald,et al.  Pharmacokinetics and Pharmacodynamics of Tenecteplase: Results from a Phase II Study in Patients with Acute Myocardial Infarction , 2000, Journal of clinical pharmacology.

[22]  A. Siegbahn,et al.  Age Dependence of Blood Fibrinolytic Components and the Effects of Low-Dose Oral Contraceptives on Coagulation and Fibrinolysis in Teenagers , 1988, Thrombosis and Haemostasis.

[23]  W. Dodds,et al.  The Value of Age‐ and Sex‐Matched Controls for Coagulation Studies , 1975, British journal of haematology.

[24]  M. Manco‐Johnson,et al.  A new global assay of coagulation and fibrinolysis. , 2005, Thrombosis research.

[25]  M. Manco‐Johnson,et al.  A new euglobulin clot lysis assay for global fibrinolysis. , 2003, Thrombosis research.