Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants--Case Series and Systematic Review of Reported Cases

J Stroke Cerebrovasc Dis. 2015 Dec;24(12):2685-93. doi: 10.1016/j.jstrokecerebrovasdis.2015.07.021. Epub 2015 Nov 2.


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.

Keywords: Acute ischemic stroke; acute stroke therapy; anticoagulants; intracerebral hemorrhage; new oral anticoagulants; tPA; thrombolysis.

Publication types

  • Case Reports
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Brain Ischemia / drug therapy*
  • Female
  • Fibrinolytic Agents / adverse effects*
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Stroke / drug therapy*
  • Thrombolytic Therapy / adverse effects*
  • Tissue Plasminogen Activator / adverse effects*
  • Tissue Plasminogen Activator / therapeutic use
  • Treatment Outcome


  • Anticoagulants
  • Fibrinolytic Agents
  • Tissue Plasminogen Activator