Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis.
OBJECTIVE
To quantify the risk for bleeding complications after thrombolysis for ischemic stroke in patients on warfarin (international normalized ratio [INR] ≤ 1.7) and to put these data into perspective with previous studies.


METHODS
A total of 548 consecutive stroke patients receiving IV recombinant tissue plasminogen activator (rtPA) were prospectively evaluated and details about warfarin pretreatment were carefully recorded. Prothrombin time-based INR values were measured before thrombolysis and 6 and 24 hours thereafter. Intracranial hemorrhage occurring within 72 hours was assessed by CT examinations and defined according to National Institute of Neurological Disorders and Stroke criteria. Main outcome variables were symptomatic intracranial and major systemic bleedings.


RESULTS
Of the 548 patients, 33 (6.0%) and 14 (2.6%) experienced symptomatic intracranial and major systemic bleedings, respectively. Patients taking warfarin until the day of or day before admission (n = 15, mean ± SD INR 1.21 ± 0.32 vs 1.01 ± 1.12, p = 0.030) faced an approximately 4-fold risk for intracranial hemorrhage (20.0% vs 5.6%, unadjusted odds ratio [OR] [95% confidence interval (CI)] 4.2 [1.1-15.7], p = 0.033). Findings were similar after adjustment for age, NIH Stroke Scale score, and diabetes (adjusted OR [95% CI] 4.1 [1.0-16.1], p = 0.044) and when focusing on any major bleeding (intracranial or systemic) (unadjusted OR [95% CI] 4.1 [1.3-13.6], p = 0.019). Half of the patients with bleedings showed an INR rise above 1.7 6 hours after thrombolysis. A meta-analysis yielded confirmatory yet heterogeneous results (unadjusted OR [95% CI] derived from a random effects model, 2.31 [1.15-4.62], p = 0.018, I(2) = 58% [11%-80%]).


CONCLUSIONS
Our data suggest a statistically significant and clinically meaningful increase in the risk for symptomatic intracranial and major systemic bleedings among patients with stroke thrombolysis receiving warfarin up to the day of or day before stroke.
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Michael
M
Ruecker
Benjamin
B
Matosevic
Peter
P
Willeit
Matthias
M
Kirchmayr
Alexandra
A
Zangerle
Michael
M
Knoflach
Johann
J
Willeit
Stefan
S
Kiechl
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D014859:Warfarin; D010959:Tissue Plasminogen Activator