title: Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants--Case Series and Systematic Review of Reported Cases.
abstract: BACKGROUND
  Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature.
  
  
  METHODS
  We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post-thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding.
  
  
  RESULTS
  Between October 2010 and October 2014, 6 patients received IV-tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method: .8-21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 ± 7.8 [4-28.3] hours.
  
  
  CONCLUSIONS
  Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy.
authors.affiliation: Department of Neurology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Shahjouei
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee; Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.affiliation: Department of Neurology, University of Alabama, Birmingham, Alabama.
authors.forename: Reza
authors.initials: R
authors.lastname: Bavarsad Shahripour
authors.affiliation: College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee.
authors.forename: G Morgan
authors.initials: GM
authors.lastname: Jones
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee. Electronic address: rzand@uthsc.edu.
authors.forename: Ramin
authors.initials: R
authors.lastname: Zand
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Acute ischemic stroke; acute stroke therapy; anticoagulants; intracerebral hemorrhage; new oral anticoagulants; tPA; thrombolysis