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Chapter Fifty One - Thrombolysis

from Treatment

Published online by Cambridge University Press:  13 December 2022

Louis R. Caplan
Beth Israel Deaconess Medical Centre
Aishwarya Aggarwal
John F. Kennedy Medical Center
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Knowledge about thrombosis, the formation of clots, dates back to Virchow, who is discussed in Chapter 13. Perturbation of a vessel leads to release of a thrombokinase that catalyzes the transformation of a precursor protein prothrombin to thrombin. Thrombin, a clot-promoting protein, catalyzes the transformation of fibrinogen (another precursor protein) into fibrin. Fibrin provides the scaffolding that holds clots together. Clots are necessary for survival since they stem bleeding. Equally necessary are chemical reactions that dissolve clots. An “activator” converts plasminogen (another precursor protein) to plasmin, a powerful fibrin-dissolving, clot-dissolving enzyme. Tissue plasminogen activator (tPA) is the molecule in question. It has the special property of acting upon plasminogen only in the presence of fibrin, only where there is a clot. The process of breaking up clots is referred to as thrombolysis. Thrombolytic agents act by breaking up fibrin bridges within thrombi and, in doing so, allow blood to flow. The process is often referred to as fibrinolysis since fibrin is the main target. Fibrinolytic drugs degrade the fibrin network mesh of red erythrocyte-fibrin clots. The formation of thrombi in the body stimulates a natural fibrinolytic mechanism for thrombolysis. Plasmin is formed and its activity is concentrated at the sites of fibrin deposition. The ideal thrombolytic agent would adhere specifically to fibrin in clots and would not affect circulating fibrinogen. Lowering circulating fibrinogen levels excessively could promote bleeding.

Stories of Stroke
Key Individuals and the Evolution of Ideas
, pp. 491 - 504
Publisher: Cambridge University Press
Print publication year: 2022

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Notes and References

The early history of thrombolysis, streptokinase, and tPA is discussed in Maroo, A, Topol, EJ. The early history and development of thrombolysis in acute myocardial infarction. J. Thromb. Haemostasis 2004;2:18671870.Google ScholarGoogle ScholarGoogle ScholarGoogle Scholar
Zivin, JA, Simmons, JG. tPA for Stroke: The Story of a Controversial Drug. New York: Oxford University Press, 2011.Google Scholar
Bryan, TPJ. The rise and fall of the clot buster: A review on the history of streptokinase. Pharm. J. 2014. Available at Scholar
Sherry, S. The origin of thrombolytic therapy. J. Am. Coll. Cardiol. 1989 Oct 1;14(4):10851092.CrossRefGoogle ScholarPubMed
DeWood, MA, Spores, J, Notske, R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N. Engl. J. Med. 1980;303:897902.Google ScholarPubMed
Meyer, JS, Gilroy, J, Barnhart, MI, Johnson, JF. Therapeutic thrombolysis in cerebral thromboembolism. Neurology 1963;13:927937.Google ScholarGoogle ScholarGoogle Scholar
Donnan, GA, Davis, SM, Chambers, BR, et al. Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. JAMA 1996;276(12):961966.CrossRefGoogle ScholarPubMed
Multicenter Acute Stroke Trial-Europe Study Group: Hommel, M, Cornu, C, Boutitie, F, Boissel, JP. Thrombolytic therapy with streptokinase in acute ischemic stroke. N. Engl. J. Med. 1996;335(3):145150.Google ScholarPubMed
Fletcher, AP, Alkjersig, N, Lewis, M, Tulevski, V, Davies, A, Brooks, JE, Hardin, WB, Landau, WM, Raichle, ME. A pilot study of urokinase therapy in cerebral infarction. Stroke 1976;7:135142.Google ScholarPubMed
Collen, D, Lijnen, HR. Tissue-type plasminogen activator: A historical perspective and personal account. J. Thromb. Haemostasis 2004;2(4):541546.CrossRefGoogle ScholarPubMed
Van de Werf, F, Ludbrook, PA, Bergmann, SR, et al. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. N. Engl. J. Med. 1984;310:609613.Google ScholarGoogle Scholar
The early investigations of thrombolytic therapy are reviewed in del Zoppo, GJ, Poeck, K, Pessin, MS, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann. Neurol. 1992;32:7886.Google ScholarGoogle ScholarGoogle Scholar
Brott, T, Haley, EC, Levy, DE, et al. Urgent therapy for stroke: Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992;23:632640.Google ScholarGoogle Scholar
Levy, DE, Brott, TG, Haley, EC, et al. Factors related to intracranial hematoma formation in patients receiving t-PA for acute, ischemic stroke. Stroke 1994;25:291297.CrossRefGoogle Scholar
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;333:15811587.CrossRefGoogle Scholar
Kwatkowski, TG, Libman, RB, Frankel, M, et al. Effects of tissue plasminogen activator for acute ischemic stroke at one year. N. Engl. J. Med. 1999;340(23):17811787.CrossRefGoogle Scholar
Brott, T, Adams, HP Jr, Olinger, CP, et al. Measurements of acute cerebral infarction: A clinical examination scale. Stroke 1989;20(7):864870.Google ScholarGoogle Scholar
The European Investigators published the results of the European Cooperative Acute Stroke Study (ECASS). Hacke, W, Kaste, M, Fieschi, C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:10171025.Google ScholarGoogle ScholarGoogle Scholar
Toni, D, Lorenzano, S, Puca, E, Prencipe, M. The SITS-MOST registry. Neurol. Sci. 2006;27(suppl 3):S260S262.Google ScholarGoogle Scholar
Caplan, LR, Mohr, JP, Kistler, JP, Koroshetz, W. Thrombolysis: Not a panacea for ischemic stroke. N. Engl. J. Med. 1997;337:13091310, 1313.Google ScholarGoogle Scholar
Bhatia, R, Hill, MD, Shobha, N, Menon, B, Bal, S, Kochar, P, Watson, T, Goyal, M, Demchuk, AM. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: Real-world experience and a call for action. Stroke 2010;41:22542258.CrossRefGoogle Scholar
Thomalla, G, Simonsen, CZ, Boutitie, F, et al. WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. N. Engl. J. Med. 2018;379(7):611622.Google ScholarGoogle Scholar
Nogueira, RG, Jadhay, AP, Hausen, DG, et al. for the DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N. Engl. J. Med. 2018;378:1121.Google ScholarGoogle Scholar
Van de Werf, F, Cannon, CP, Luyten, A, et al. Safety assessment of single bolus administration of TNK-tPA in acute myocardial infarction: The ASSENT-1 trial. Am. Heart J. 1999;137:786791.Google ScholarGoogle Scholar
Huang, X, MacIsaac, R, Thompson, JL, Levin, B, Buchsbaum, R, Haley, EC, et al. Tenecteplase versus alteplase in stroke thrombolysis: An individual patient data meta-analysis of randomized controlled trials. Int. J. Stroke 2016 11:534543.Google ScholarGoogle ScholarGoogle Scholar
Hacke, W, Zeumer, H, Ferbert, A, Bruckman, H. Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1998;29:12161222.Google Scholar
del Zoppo, GJ, Higashida, RT, Furlan, AJ, et al. PROACT: A phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke 1998;29:411.CrossRefGoogle ScholarPubMed
Furlan, AJ, Higashida, RT, Wechsler, L, et al. PROACT II. Intra-arterial pro-urokinase for acute ischemic stroke: A randomized controlled trial. JAMA 1999;282;20032011.CrossRefGoogle ScholarPubMed
Furlan, AJ, Higashida, R, Katzan, I, Abou-Chebl, A, Russman, A. Intra-arterial thrombolysis in acute ischemic stroke. In Lyden, PD (ed.), Thrombolytic Therapy for Acute Stroke, 2nd ed. Totowa, NJ: Humana Press, 2005, pp. 159184.CrossRefGoogle Scholar
Lindberg, PJ, Mattle, HP. Therapy of basilar artery occlusion: A systematic analysis comparing intra-aerterial and intravenous thrombolysis. Stroke 2006;37:922928.Google ScholarGoogle Scholar

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