title: Changes in Activated Thrombin-Activatable Fibrinolysis Inhibitor Levels Following Thrombolytic Therapy in Ischemic Stroke Patients Correlate with Clinical Outcome.
abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA).
  
  
  
  In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0-1) and unfavorable (2-6) outcomes.
  
  
  
  A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003).
  
  
  
  These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment.
authors.affiliation: Laboratory Haemostasis, Inserm UMR 1062, Inra UMR 1260, Aix Marseille University, Marseille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Christophe
authors.initials: C
authors.lastname: Gaudin
authors.forename: Philippe
authors.initials: P
authors.lastname: Grosjean
authors.forename: Valérie
authors.initials: V
authors.lastname: Martin
authors.forename: Serge
authors.initials: S
authors.lastname: Timsit
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mahagne
authors.forename: Vincent
authors.initials: V
authors.lastname: Larrue
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Mathieu
authors.initials: M
authors.lastname: Zuber
authors.forename: Raf
authors.initials: R
authors.lastname: Brouns
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.forename: Yves
authors.initials: Y
authors.lastname: Donazzolo
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Cho
authors.forename: Laurent
authors.initials: L
authors.lastname: Suissa
authors.forename: Laura
authors.initials: L
authors.lastname: Mechtouff
authors.forename: Laurent
authors.initials: L
authors.lastname: Derex
authors.forename: Pierre
authors.initials: P
authors.lastname: Suchon
authors.forename: Anna
authors.initials: A
authors.lastname: Mezzapesa
authors.forename: Norbert
authors.initials: N
authors.lastname: Nighoghossian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D025901:Carboxypeptidase B2 / Q000097:blood*; D016022:Case-Control Studies; D004185:Disability Evaluation; D005060:Europe; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator