title: Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis.
abstract: OBJECTIVE
  Prominent fibrinogen cleavage by recombinant tissue plasminogen activator and formation of fibrinogen degradation products with anticoagulant properties was proposed to amplify the risk of thrombolysis-related bleeding complications, but supportive evidence mainly derived from studies on myocardial infarction.
  
  
  METHODS
  This study included 547 consecutive stroke patients treated with recombinant tissue plasminogen activator, who underwent repeated assessment of fibrinogen levels before and 6 hours after thrombolysis. Symptomatic intracranial hemorrhages were ascertained using National Institute of Neurological Disorders and Stroke criteria.
  
  
  RESULTS
  Intracranial hemorrhage or systemic bleeding events manifested in 47 patients (8.6%). A decrease ≥200 mg/dL in the fibrinogen level 6 hours after thrombolysis emerged as a significant and independent predictor for bleeding risk (multivariable odds ratio [95% confidence interval] 4.53 [2.39-8.60], p < 0.001). The population-attributable risk was 39.9% (95% confidence interval, 19.0-60.2) for any major bleeding, causality assumed, and surpassed 50% in patients with less severe strokes (NIH Stroke Scale score ≤16). Quantification of fibrinogen depletion after stroke thrombolysis significantly improved routine risk prediction of bleeding complications as indicated by an increase in the C-statistics from 0.712 to 0.798 (p = 0.015) and a net reclassification index of 0.341 (p < 0.001). A prospective bicenter validation sample (n = 148) corroborates the key findings of this study and suggests positive and negative predictive values of fibrinogen depletion for any major bleeding of 29.2% and 93.5%.
  
  
  CONCLUSIONS
  This study lends strong support to the concept that prominent fibrinogen turnover after IV stroke thrombolysis-a condition termed "early fibrinogen degradation coagulopathy"-is a relevant cause of major bleeding complications. Rigorous testing of more fibrin-specific thrombolytic agents in the setting of acute stroke is warranted.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Matosevic
authors.forename: Michael
authors.initials: M
authors.lastname: Knoflach
authors.forename: Philipp
authors.initials: P
authors.lastname: Werner
authors.forename: Raimund
authors.initials: R
authors.lastname: Pechlaner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zangerle
authors.forename: Michael
authors.initials: M
authors.lastname: Ruecker
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirchmayr
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001778:Blood Coagulation Disorders / Q000188:drug therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator