Thrombolysis in Acute Cerebrovascular Disease: Indications and Limitations

Introduction

Large-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction (AMI). As most ischemic strokes are thromboembolic in origin,¹ there appears to be a rationale for the use of thrombolytic agents in the management of ischemic stroke.

Thrombolytic agents differ in their mechanisms of action, but in general, they act by promoting the conversion of plasminogen into plasmin, resulting in fibrin degradation and clot dissolution. Streptokinase and recombinant tissue plasminogen activator (rt-PA) are the agents that have been the most widely investigated in stroke studies. Ancrod, the active agent in the venom of the Malayan pit viper, is primarily considered an anticoagulant, although it does stimulate endogenous t-PA release from the vascular endothelium and may enhance local thrombolysis. Urokinase is used in local, intra-arterial thrombolysis but has not been subjected to large clinical trials since computed tomography (CT) diagnosis became widely available.

• References

• 1 Woo KS, White HD. Comparative tolerability profiles of thrombolytic agents. Drug Saf 1993; 8: 19-29.
• 2 Del Zoppo GJ, Zeumer H, Harker LA. Thrombolytic therapy in stroke: possibilities and hazards. Stroke 1986; 17: 595-607.
• 3 Haley Jr. EC. Thrombolytic therapy for acute ischemic stroke. Clin Neuropharmacol 1993; 16: 179-194.
• 4 von Kummer R, Meyding-Lamade U, Forsting M, Rosin L, Rieke K, Hacke W, Sartor K. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol 1994; 15: 9-15.
• 5 Hacke W, Zeumer H, Ferbert A, Bruckmann H, del Zoppo GJ. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988; 19: 1216-1222.
• 6 del Zoppo GJ, Pessin MS, Mori E, Hackie W. Thrombolytic intervention in acute thrombotic and embolic stroke. Semin Neurol 1991; 11: 368-384.
• 7 Hacke W, Kaste M, Fieschi C, Toni P, Lesaffre E, von Hummer R, Boysen G, Blubmki E, Hoxter G, Mahagne MH. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274: 1017-1025.
• 8 Hacke W. Thrombolytic therapy in acute ischemic stroke: an update. Fibrinolysis 1994; 8 (Suppl. 01) 216-220.
• 9 Mori E, Yoneda Y, Tabuchi M, Yoshida T, Ohkawa S, Ohsumi Y, Kitano K, Tsutsumi A, Yamadori A. Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology 1992; 42: 976-982.
• 10 Yamaguchi T, Hayakawa T, Kikichi H. et al. In: Hacke W, del Zoppo GJ, Hirschberg M. eds. Thrombolytic Therapy in Acute Ischemic Stroke. Berlin: SpringerVerlag; 1991: 168-174.
• 11 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581-1587.
• 12 The Multicenter Acute Stroke Trial Europe Study Group. Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med 1996; 335: 145-150.
• 13 Multicentre Acute Stroke Trial - Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin and combination of both in acute ischaemic stroke. Lancet 1995; 346: 1509-1514.
• 14 Donnan GA, Davis SM, Chambers BR, Gates PC, Hankey GJ, McNeil JJ, Rosen D, Stewart-Wynne EG, Tuck RR. Trials of streptokinase in acute ischaemic stroke. Lancet 1995; 345: 578-579.
• 15 Hacke W, Kaste M, Fieschi C, Meier P, Larrue V, Blubmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. for the Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998; 352: 1245-1251.