title: Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism.
abstract: BACKGROUND
  We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)-catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE).
  
  
  METHODS
  Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, α2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405).
  
  
  RESULTS
  Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT.
  
  
  CONCLUSIONS
  The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT.
authors: Louisiana State University, Health Sciences Center, New Orleans, United States of America.
authors: William B
authors: WB
authors: Stubblefield
authors: Indiana University School of Medicine, Indianapolis, United States of America.
authors: Nathan J
authors: NJ
authors: Alves
authors: University of Utah School of Medicine, Salt Lake City, United States of America.
authors: Matthew T
authors: MT
authors: Rondina
authors: Department of Emergency Medicine, and Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
authors: Jeffrey A
authors: JA
authors: Kline
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000097:blood; D016022:Case-Control Studies; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D063285:Fibrin Clot Lysis Time; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D061214:Patient Safety; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011655:Pulmonary Embolism / Q000628:therapy*; D011788:Quality of Life; D012044:Regression Analysis; D012306:Risk; D000077785:Tenecteplase; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000378:metabolism* / Q000627:therapeutic use; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase