title: Admission fibrinolytic profile is associated with symptomatic hemorrhagic transformation in stroke patients treated with tissue plasminogen activator.
abstract: OBJECTIVE
  Symptomatic intracranial hemorrhage (SICH) is the most feared complication after tissue plasminogen activator (tPA) stroke treatment. Endogenous fibrinolysis inhibitors play an essential role in the coagulation/fibrinolysis balance and may be involved in the bleeding process. We aim to determine the predictive value of pretreatment levels of fibrinolysis inhibitors (PAI-1, lipoprotein(a), TAFI, and homocysteine) on SICH.
  
  
  METHODS
  Consecutive tPA-treated stroke patients with middle cerebral artery occlusion were studied. Baseline blood samples were obtained just before tPA administration and fibrinolysis inhibitors were determined. A second computed tomography (CT) scan was obtained at 24 hours or when a neurological worsening occurred to rule out SICH.
  
  
  RESULTS
  Seventy-seven patients (40% women, age 75 years) were studied. Median admission National Institutes of Health Stroke Scale was 17 (range, 7 to 22) and mean time to treatment was 160 minutes. Six patients (7.9%) presented with a SICH. In analyses based on clinical and CT variables, no relation could be found with SICH. When laboratory data were analyzed, patients who experienced SICH showed lower baseline PAI-1 (21.7+/-3.5 ng/mL versus 31.8+/-12.1 ng/mL; P<0.01) and higher TAFI (216.7+/-78.4% versus 162.1+/-54.2%; P=0.03). Homocysteine and lipoprotein(a) were not related to SICH. The only factors associated with SICH were TAFI >180% (OR, 12.9; CI, 1.41 to 118.8; P=0.02) and PAI-1 <21.4 ng/mL (OR, 12.75; CI, 1.17 to 139.2; P=0.04). The combination of admission PAI-1 <21.4 ng/mL and TAFI >180% had a sensibility of 75% and a specificity of 97.6% (P<0.01) predicting SICH, with a positive predictive value of 75% and negative predictive value of 97.6%.
  
  
  CONCLUSIONS
  Baseline PAI-1 and TAFI levels predict SICH after stroke tPA therapy. In the future, these biomarkers could be used to improve thrombolysis safety.
authors.affiliation: Neurovascular Research Laboratory, Neurovascular Unit Hospital Vall d'Hebron, Barcelona, Spain. marcriboj@hotmail.com
authors.forename: Marc
authors.initials: M
authors.lastname: Ribo
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: Esteban
authors.initials: E
authors.lastname: Santamarina
authors.forename: Manuel
authors.initials: M
authors.lastname: Quintana
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers; D025901:Carboxypeptidase B2 / Q000097:blood; D002543:Cerebral Hemorrhage / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D005342:Fibrinolysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D015415:Biomarkers; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D006710:Homocysteine; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator