Intravenous administration of tissue plasminogen activator (tPA) is currently the only approved therapy for acute ischemic stroke. The drug works by splitting plasminogen into plasmin, ultimately leading to fibrin degradation at the site of cerebral artery occlusion. Even today, more than 10 years after the drug was approved in the United States (and subsequently around the world), its use has been hampered by the fear of inducing symptomatic intracerebral hemorrhage (SICH). This adverse event was seen in 6% of patients treated in the original National Institute of Neurological Disorders and Stroke trial1 that led to tPA's approval and was subsequently confirmed in multiple postmarketing studies.2,3 The predictors of SICH after tPA administration are well known: severe stroke (high National Institute of Health Stroke Scale score) and large hypodensity on the admission computed tomography. Other possible predictors include advanced age, elevated blood glucose, a platelet count of less than 50 000/mL, and systolic blood pressure above 180 mm Hg.2,4 Previous works have examined the relationship between prior antiplatelet (AP) therapy and SICH after tPA administration. Notably, in the National Institute of Neurological Disorders and Stroke tPA trial, there was no association between prior aspirin therapy and SICH.4 Another multicenter stroke survey showed an association of SICH with aspirin therapy that was lost after controlling for clinical and laboratory variables.2 Contrary to that, in this issue of Archives, Uyttenboogaart et al5 report a surprisingly high rate of SICH after tPA administration in patients undergoing long-term AP therapy. In their cohort of 309 patients derived from a single center in the Netherlands, AP therapy (mostly aspirin or an aspirin and dipyridamole combination) before the stroke was associated with a 13.5% rate of SICH compared with 2.8% in patients without AP therapy. Drug compliance was not assessed in this study. As expected, patients undergoing AP therapy were older and had more vascular risk factors than patients not taking AP drugs. There were no differences in stroke severity, stroke subtype, blood pressure, blood glucose, or early changes on the admission computed tomographic scan. Despite the high rate of SICH, AP therapy was associated with an odds ratio of 2 for a favorable outcome. How does one settle these seemingly contradictory results and what lessons can we draw from this observation? Let us first look at the role of platelets in acute ischemic stroke.
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