A North American retrospective study was conducted to determine whether warfarin-treated patients with an INR < 1.7 who receive intravenous tissue plasminogen activator (TPA) for acute ischaemic stroke are at increased risk for symptomatic intracerebral haemorrhage (sICH).

The study included 107 patients with the following characteristics:

• Mean age 69.2 years
• 43.9% men
• Median National Institutes of Health Stroke Scale score (NIHSS) = 14
• Median onset-to-treatment time = 140 minutes
• Baseline warfarin use = 12.1%
• Median INR = 1.04 (range, 0.82-1.61)

The overall rate of sICH was 6.5%, but it was higher among patients taking warfarin compared with those not taking warfarin at baseline (30.8% vs 3.2%, respectively; p = 0.004). Baseline warfarin use remained strongly associated with sICH (p = 0.004) after adjusting for relevant covariates, including age, atrial fibrillation, NIHSS, and INR.

The researchers conclude from this retrospective study that despite an INR < 1.7, warfarin-treated patients are more likely than those not taking warfarin to experience sICH following treatment with iv TPA for acute ischaemic stroke. They acknowledge their conclusions are limited by the following study design and methodology.

• Small sample size
• Tertiary referral bias toward a "sicker" cohort
• Inability to assess effect of early infarct changes on sICH as not all initial CT scans were available for review
• Serial INRs were not performed in every patient in the hours and days following IV TPA
• Inability to assess whether enhanced recanalisation mediates this relationship between warfarin and sICH because angiography was not uniformly performed in each patient
• Use of European Cooperative Acute Stroke Study definition of sICH so unable to report the prevalence of sICH by other definitions

Given these limitations, they stress that the study should serve as a hypothesis-generating report that requires confirmation in larger cohorts, with more extensive adjustment for confounding variables.