Factors Related to Intracranial Hematoma Formation in Patients Receiving t-PA for Acute Ischemic Stroke

Abstract

Tissue plasminogen activator (rt-PA) is used widely for acute myocardial infarction (MI) in the United States and is currently undergoing clinical trial in acute, ischemic stroke. Both theory and practice have raised concerns about intracranial bleeding induced by rt-PA, so that in the United States, rt-PA is contraindicated in MI patients with a “history of a cerebrovascular accident.” An open-label, Phase I study sponsored by the NIH recently assessed the safety and efficacy of single-chain rt-PA. The trial required hyper-acute treatment, initially within 90 min and subsequently in a 91- to 180-min time window [6]; results of these trials have been published and suggest that rt-PA is relatively safe and may be clinically effective. Nonetheless, complicating intracerebral hematomas did occur, 3 in the 0- to 90-min group of 74 patients and 2 in the 90- to 180- min group of 20 patients. Analysis of the 74 0- to 90-min patients suggested that the risk of intracerebral hematoma increased with increasing rt-PA dose [3], but with merely 3 patients, only limited analyses were possible. Although total numbers are still small, the existence of 5 hematoma patients now permits a more detailed effort to identify risk factors associated with hemorrhage.