Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke.

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Abstract
There is little reported of the safety and efficacy of high-dose intravenous recombinant tissue plasminogen activator (alteplase) in combination with heparin anticoagulation in patients presenting with acute ischemic stroke. Thirty-two patients with severe hemispheric stroke syndrome caused by angiographically proven middle cerebral artery and/or intracranial internal carotid artery occlusion were treated with 100 mg alteplase by intravenous infusion over 90 minutes within a mean +/- SD of 226 +/- 68 minutes after symptom onset. Recanalization was assessed by digital subtraction angiography in all patients immediately after treatment and by transcranial Doppler monitoring (n = 30) and/or a third angiogram (n = 5) 12-24 hours later. Complete or partial reperfusion was observed in 11 patients (34%) 90 minutes after the initiation of alteplase infusion and in 17 patients (53%) within 12-24 hours. Hemorrhagic infarction without clinical deterioration was detected by follow-up computed tomography in nine patients (28%). Fatal parenchymal hemorrhage occurred in three patients (9%) with huge middle cerebral artery infarcts. Serious hemorrhage from the puncture site occurred in two patients (6%). Good clinical outcome correlated with reperfusion (p less than 0.05) and the presence of grade 2 collateral blood flow (p less than 0.01). When 100 mg of recombinant tissue plasminogen activator was given within the first 6 hours of acute stroke together with heparin the incidence of deleterious hemorrhage was less than 10%. Reperfusion and effective collateral blood flow seem to be two important factors associated with a small infarct volume and good clinical outcome.