UMEM Educational Pearls

Category: Pharmacology & Therapeutics

Title: tPA for Acute Ischemic Stroke Patients on Warfarin

Keywords: alteplase, tPA, warfarin, INR, ischemic stroke (PubMed Search)

Posted: 7/2/2012 by Bryan Hayes, PharmD (Emailed: 7/7/2012) (Updated: 7/7/2012)
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  • IV alteplase (tPA) has many contraindications when administered for acute ischemic stroke. Among them is a history of warfarin use with INR > 1.7 (0-3 hours) or any history of warfarin use regardless of INR (3-4.5 hours).
  • A recent retrospective analysis of a major stroke registry compared the risk of symptomatic intracerebral hemorrhage (ICH) following tPA in patients on warfarin with an INR < 1.7 (n - 1,802) with patients not on warfarin therapy (n = 21,635).
  • After adjusting for differences in the two populations, the authors found no increased symptomatic ICH risk in patients with preadmission warfarin use (5.7% vs. 4.6%, p = 0.94).

Issue 1: Mean INR in study patients was only 1.22 (median 1.2). An INR of 1.2 represents very little actual anticoagulation.

Issue 2: In the small subgroup of patients with INR 1.5 to 1.7 (n = 269) there was a higher risk of ICH (7.8%), but did not reach statistical significance (it was significant in the unadjusted risk population).

Bottom line: Patients with INRs < 1.5 may be ok to receive tPA. Patients with INRs 1.5 or greater need further study.


Xian Y, Liang L, Smith EE, et al. Risk of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated with Intravenous Tissue Plasminogen Activator. JAMA. 2012;307(24):2600-8.

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