CLINICAL-FEATURES AND PATHOGENESIS OF INTRACEREBRAL HEMORRHAGE AFTER RT-PA AND HEPARIN-THERAPY FOR ACUTE MYOCARDIAL-INFARCTION - THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION (TIMI)-II PILOT AND RANDOMIZED CLINICAL-TRIAL COMBINED EXPERIENCE

Parenchymatous intracerebral hemorrhage (ICH) is a serious, infrequent complication of thrombolytic therapy for acute myocardial, infarction . We studied the clinical and radiologic features, manner of presentat ion, associated factors, and temporal course in 23 patients with ICH a ssociated with 150 mg or 100 mg recombinant tissue-type plasminogen ac tivator (rt-PA) and heparin therapy for acute myocardial infarction in the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomi zed Clinical Trial. In TIMI II, 13 of the 23 ICH patients developed or maintained systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg during the rt-PA infusion and before the onset of neurologic symptoms. Six pa tients (26%) had life-threatening ventricular arrhythmias, five before onset of neurologic symptoms. A decreased level of consciousness was the earliest neurologic abnormality in 15 (65%) and the most common in itial physical finding (in 19, or 82%). Onset was usually gradual (70% ), but time to maximal deficit was frequently (61%) within 6 hours of onset. The locations of the primary ICH sites were lobar in 16 (70%), thalamic in four (17%), and brainstem-cerebellum in three (13%), but t he putamen was never the primary site. Multiple lobar hemorrhages occu rred in six cases (26%). The timing and size of ICH was similar among patients treated with 150 mg rt-PA and 100 mg rt-PA. Brain CT demonstr ated an arteriovenous malformation in one case. Four patients had hypo fibrinogenemia, which was profound in three patients. Pathologic findi ngs were available for five patients. Of these, three patients had cer ebral amyloid angiopathy, and one had hemorrhagic transformation of an ischemic cerebral infarction found at autopsy. We conclude that ICH f ollowing rt-PA and heparin therapy for acute myocardial infarction pre sents as a distinctive clinical syndrome. Intracerebral bleeding after combined thrombolytic and antithrombotic therapy may be associated wi th cerebral amyloid angiopathy and other vascular lesions. Acute or pe rsistent hypertension before or during rt-PA infusion, life-threatenin g ventricular arrhythmias, and hypofibrinogenemia, either alone or in combination, may play roles in some cases. Care should be exercised wh en considering thrombolytic therapy for patients with risk factors for ICH.