title: Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke.
abstract: OBJECTIVE
  We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage.
  
  
  METHODS
  Venous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences.
  
  
  RESULTS
  Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase.
  
  
  CONCLUSIONS
  In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926.
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: Xuya
authors.initials: X
authors.lastname: Huang
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: Fiona Catherine
authors.initials: FC
authors.lastname: Moreton
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Kalladka
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: Bharath Kumar
authors.initials: BK
authors.lastname: Cheripelli
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: Rachael
authors.initials: R
authors.lastname: MacIsaac
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
authors.forename: R Campbell
authors.initials: RC
authors.lastname: Tait
authors.affiliation: From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.). keith.muir@glasgow.ac.uk.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
keywords: alteplase; cerebral hemorrhage; factor V; prothrombin time; stroke; tenecteplase; thrombolysis