Abstract
Tissue plasminogen activator is used in the management of acute arterial ischemic stroke, myocardial infarction, and massive pulmonary embolism. tPA has been shown to improve outcomes in these conditions, but its use is not without risk. Significant bleeding tends to happen at a fairly low rate overall; however, it can have serious complications necessitating prompt recognition and urgent intervention. The most concerning complication is massive intracerebral hemorrhage which carries a high risk of morbidity and mortality. There is limited data available to support best practice in the management of tPA-related hemorrhage and there is wide variation in current practice. Expert opinion supports correction of coagulopathy with cryoprecipitate. Additionally, tranexamic acid or ε-aminocaproic acid may be considered for acute treatment. Surgical options exist although current studies examining surgery in this setting are inconclusive. Future research is necessary to establish most effective treatment for the management of bleeding associated with tPA in order to minimize consequences and improve functional outcome of surviving patients.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Collen D, Lijnen HR. Tissue-type plasminogen activator: a historical perspective and personal account. J Thromb Haemost JTH. 2004;2(4):541–6.
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(24):1581–7.
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29.
Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788–830.
Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113(11):e463–654.
McIntosh SE, Opacic M, Freer L, Grissom CK, Auerbach PS, Rodway GW, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite: 2014 update. Wilderness Environ Med. 2014;25(4 Suppl):S43–54.
Davies HE, Davies RJO, Davies CWH, BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(2):41–53.
Gravanis I, Tsirka SE. Tissue-type plasminogen activator as a therapeutic target in stroke. Expert Opin Ther Targets. 2008;12(2):159–70.
Verstraete M, Bounameaux H, de Cock F, Van de Werf F, Collen D. Pharmacokinetics and systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator (rt-PA) in humans. J Pharmacol Exp Ther. 1985;235(2):506–12.
Zhang J, Yang Y, Sun H, Xing Y. Hemorrhagic transformation after cerebral infarction: current concepts and challenges. Ann Transl Med. 2014;2(8):81.
Wang W, Li M, Chen Q, Wang J. Hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke: mechanisms, models, and biomarkers. Mol Neurobiol. 2014;52(3):1572–9.
O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv Off J Soc Card Angiogr Interv. 2013;82(1):E1–27.
Gebel JM, Sila CA, Sloan MA, Granger CB, Mahaffey KW, Weisenberger J, et al. Thrombolysis-related intracranial hemorrhage: a radiographic analysis of 244 cases from the GUSTO-1 trial with clinical correlation. Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries. Stroke J Cereb Circ. 1998;29(3):563–9.
Shimohata T, Kanazawa M, Kawamura K, Takahashi T, Nishizawa N. Therapeutic strategies to atttenuate hemorrhagic transformation after tissue plasminogen activator treatment for acute ischemic stroke. Neurol Clin Neurosci. 2013;1(6):201–8.
Fonarow GC, Zhao X, Smith EE, Saver JL, Reeves MJ, Bhatt DL, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA. 2014;311(16):1632–40.
Hemphill JC, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke J Cereb Circ. 2015;46(7):2032–60.
Zazulia AR, Diringer MN, Videen TO, Adams RE, Yundt K, Aiyagari V, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2001;21(7):804–10.
Goldstein JN, Marrero M, Masrur S, Pervez M, Barrocas AM, Abdullah A, et al. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010;67(8):965–9.
Alderazi YJ, Barot NV, Peng H, Vahidy FS, Navalkele DD, Sangha N, et al. Clotting factors to treat thrombolysis-related symptomatic intracranial hemorrhage in acute ischemic stroke. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc. 2014;23(3):e207–14.
Trouillas P, Derex L, Philippeau F, Nighoghossian N, Honnorat J, Hanss M, et al. Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: a study of 157 cases. Stroke J Cereb Circ. 2004;35(6):1323–8.
Stricker RB, Wong D, Shiu DT, Reyes PT, Shuman MA. Activation of plasminogen by tissue plasminogen activator on normal and thrombasthenic platelets: effects on surface proteins and platelet aggregation. Blood. 1986;68(1):275–80.
Frontera JA, Lewin Iii JJ, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage : a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6–46.
Stanworth SJ. The evidence-based use of FFP and cryoprecipitate for abnormalities of coagulation tests and clinical coagulopathy. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2007;2007:179–86.
Yaghi S, Eisenberger A, Willey JZ. Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment. JAMA Neurol. 2014;71(9):1181–5.
French KF, White J, Hoesch RE. Treatment of intracerebral hemorrhage with tranexamic acid after thrombolysis with tissue plasminogen activator. Neurocrit Care. 2012;17(1):107–11.
Naidech AM, Jovanovic B, Liebling S, Garg RK, Bassin SL, Bendok BR, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke J Cereb Circ. 2009;40(7):2398–401.
Gross H, Sung G, Weingart SD, Smith WS. Emergency neurological life support: acute ischemic stroke. Neurocrit Care. 2012;17 Suppl 1:S29–36.
Neufeld EJ, Négrier C, Arkhammar P, Benchikh el Fegoun S, Simonsen MD, Rosholm A. Safety update on the use of recombinant activated factor VII in approved indications. Blood Rev. 2015;29 Suppl 1:34–41.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127–37.
Mayer SA, Davis SM, Skolnick BE, Brun NC, Begtrup K, Broderick JP, et al. Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII? Stroke J Cereb Circ. 2009;40(3):833–40.
Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H, et al. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost JTH. 2008;6(4):622–31.
Bershad EM, Suarez JI. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care. 2010;12(3):403–13.
Vermeer C, Schurgers LJ. A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin North Am. 2000;14(2):339–53.
Ho CH, Wang SP. Serial thrombolysis-related changes after thrombolytic therapy with TPA in patients with acute myocardial infarction. Thromb Res. 1990;58(3):331–41.
Matrat A, De Mazancourt P, Derex L, Nighoghossian N, Ffrench P, Rousson R, et al. Characterization of a severe hypofibrinogenemia induced by alteplase in two patients thrombolysed for stroke. Thromb Res. 2013;131(1):e45–8.
Takeuchi S, Wada K, Nawashiro H, Arimoto H, Ohkawa H, Masaoka H, et al. Decompressive craniectomy after intravenous tissue plasminogen activator administration for stroke. Clin Neurol Neurosurg. 2012;114(10):1312–5.
Mahaffey KW, Granger CB, Sloan MA, Green CL, Gore JM, Weaver WD, et al. Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and tissue-plasminogen activator (tPA) for Occluded Coronary Arteries. Am Heart J. 1999;138(3 Pt 1):493–9.
Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet Lond Engl. 2005;365(9457):387–97.
Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet Lond Engl. 2013;382(9890):397–408.
Lei C, Lin S, Zhang C, Tao W, Dong W, Hao Z, et al. Activation of cerebral recovery by matrix metalloproteinase-9 after intracerebral hemorrhage. Neuroscience. 2013;230:86–93.
Sumii T, Lo EH. Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke J Cereb Circ. 2002;33(3):831–6.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Erklauer, J.C. (2016). Thrombolytic Therapy: tPA-Induced Bleeding. In: Teruya, J. (eds) Management of Bleeding Patients. Springer, Cham. https://doi.org/10.1007/978-3-319-30726-8_26
Download citation
DOI: https://doi.org/10.1007/978-3-319-30726-8_26
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-30724-4
Online ISBN: 978-3-319-30726-8
eBook Packages: MedicineMedicine (R0)