title: Admission fibrinolytic profile predicts clot lysis resistance in stroke patients treated with tissue plasminogen activator.
abstract: Endogenous fibrinolysis inhibitors may be involved in t-PA resistance, decreasing stroke thrombolysis benefits. We aim to determine the impact of pretreatment levels of plasminogen activator inhibitor (PAI-1), lipoprotein(a), thrombin-activatable fibrinolysis inhibitor (TAFI) and homocysteine on arterial recanalization and outcome. Forty-four consecutive patients with acute proximal middle cerebral artery occlusion were studied, including assessment of transcranial Doppler artery patency. The neurological status was determined by NIH Stroke Scale (NIHSS) and long-term outcome with modified Rankin Scale (mRS). Patients who recanalized after t-PA infusion had lower PAI-1 levels than those who remained occluded. Similarly, patients who achieved dramatic clinical recovery at 12 hours exhibited significantly lower PAI-1 levels as those independent (mRS< or =2) at third month. We observed a trend towards lower lipoprotein p(a) in patients who achieved recanalization at 1 hour, whereas no relation was found between TAFI or homo-cysteine levels and recanalization. After a regression model was applied the only independent predictor of thrombolysis resistance was baseline PAI-1>34 ng/ml, such that high PAI-1 levels interfere with tPA-induced recanalization in stroke, predicting a higher susceptibility towards clot-lysis resistance and poor out-come.
authors.affiliation: Neurovascular Unit Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, 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: José
authors.initials: J
authors.lastname: Alvarez-Sabín
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004351:Drug Resistance; D005260:Female; D005342:Fibrinolysis; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator