Abstract
To determine the clinical implications of hemorrhagic transformation (HT) after thrombolysis, 241 eligible patients receiving alteplase for acute ischemic stroke were studied. HT was classified, according to the European Cooperative Acute Stroke Study criteria, as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH). Symptomatic intracranial hemorrhage (SICH) was defined according to the National Institute of Neurological Disorders and Stroke study. A novel classification, clinically significant intracranial hemorrhage (CSICH) was defined as HTs associated with an unfavorable clinical outcome (modified Rankin Scale 5–6) at 3 months. For all subtypes of HT, we found that patients receiving alteplase were more often in the standard-dose group (0.90 ± 0.02 mg/kg) than in the lower dose group (0.72 ± 0.07 mg/kg). PH and SICH were related to an unfavorable clinical outcome, while HI was not. There was a positive trend between age and CSICH in patients receiving the standard dose (P = 0.0101), and between alteplase dose and CSICH in patients ≥70 years old (P = 0.0228). All PHs (including asymptomatic PHs) and symptomatic HIs have been found to be associated with unfavorable outcome, and for this reason defined as CSICH. Independent predictors of CSICH were age ≥70 years and the standard dose of alteplase. Further studies of thrombolysis for ischemic stroke with different doses of alteplase are warranted.
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References
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587
Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P (1998) Randomized double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 352:1245–1251
Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G, SITS-MOST investigators, (2007) Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 369:275–282
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D, ECASS Investigators (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329
von Kummer R (2002) Brain hemorrhage after thrombolysis: good or bad? Stroke 33:1446–1447
Fiorelli M, Bastianello S, von Kummer R, del Zoppo GJ, Larrue V, Lesaffre E, Ringleb AP, Lorenzano S, Manelfe C, Bozzao L (1999) Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Stroke 30:2280–2284
Berger C, Fiorelli M, Steiner T, Schäbitz WR, Bozzao L, Bluhmki E, Hacke W, von Kummer R (2001) Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic? Stroke 32:1330–1335
Dzialowski I, Pexman JH, Barber PA, Demchuk AM, Buchan AM, Hill MD, Investigators CASES (2007) Asymptomatic hemorrhage after thrombolysis may not be benign: prognosis by hemorrhage type in the Canadian alteplase for stroke effectiveness study registry. Stroke 38:75–79
Kimura K, Iguchi Y, Shibazaki K, Aoki J, Terasawa Y (2008) Hemorrhagic transformation of ischemic brain tissue after t-PA thrombolysis as detected by MRI may be asymptomatic, but impair neurological recovery. J Neurol Sci 272:136–142
Thanvi BR, Treadwell S, Robinson T (2008) Haemorrhagic transformation in acute ischaemic stroke following thrombolysis therapy: classification, pathogenesis and risk factors. Postgrad Med J 84:361–367
Derex L, Nighoghossian N (2008) Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update. J Neurol Neurosurg Psychiatry 79:1093–1099
Yamaguchi T, Mori E, Minematsu K, Nakagawara J, Hashi K, Saito I, Shinohara Y, Japan Alteplase Clinical Trial (J-ACT) Group (2006) Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT). Stroke 37:1810–1815
Chao AC, Hsu HY, Chung CP, Liu CH, Chen CH, Teng MM, Peng GS, Sheng WY, Hu HH, Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group (2010) Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study. Stroke 41:885–890
Zhou XY, Wang SS, Collins ML, Davis SM, Yan B (2010) Efficacy and safety of different doses of intravenous tissue plasminogen activator in Chinese patients with ischemic stroke. J Clin Neurosci 17:988–992
Larrue V, von Kummer RR, Müller A, Bluhmki E (2001) Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke 32:438–441
Molina CA, Alvarez-Sabín J, Montaner J, Abilleira S, Arenillas JF, Coscojuela P, Romero F, Codina A (2002) Thrombolysis-related hemorrhagic infarction: a marker of early reperfusion, reduced infarct size, and improved outcome in patients with proximal middle cerebral artery occlusion. Stroke 33:1551–1556
Fiehler J, Remmele C, Kucinski T, Rosenkranz M, Thomalla G, Weiller C, Zeumer H, Röther J (2005) Reperfusion after severe local perfusion deficit precedes hemorrhagic transformation: an MRI study in acute stroke patients. Cerebrovasc Dis 19:117–124
Larrue V, von Kummer R, del Zoppo G, Bluhmki E (1997) Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. Stroke 28:957–960
Trouillas P, von Kummer R (2006) Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke. Stroke 37:556–561
Levy DE, Brott TG, Haley EC Jr, Marler JR, Sheppard GL, Barsan W, Broderick JP (1994) Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke. Stroke 25:291–297
Chao AC, Teng MM, Chung CP, Weng HY, Chen YY, Yang FY, Wang LM, Hu HH (2007) Preliminary efficacy report of a novel thrombolytic agent for acute ischemic stroke within a 5-hour window. CNS Drugs 21:937–946
Hacke W, Furlan AJ, Al-Rawi Y, Davalos A, Fiebach JB, Gruber F, Kaste M, Lipka LJ, Pedraza S, Ringleb PA, Rowley HA, Schneider D, Schwamm LH, Leal JS, Söhngen M, Teal PA, Wilhelm-Ogunbiyi K, Wintermark M, Warach S (2009) Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 8:141–150
Tanne D, Gorman MJ, Bates VE, Kasner SE, Scott P, Verro P, Binder JR, Dayno JM, Schultz LR, Levine SR (2000) Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older: the tPA stroke survey experience. Stroke 31:370–375
Sylaja PN, Cote R, Buchan AM, Hill MD, Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators (2006) Thrombolysis in patients older than 80 years with acute ischaemic stroke: Canadian Alteplase for Stroke Effectiveness Study. J Neurol Neurosurg Psychiatry 77:826–829
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The first author (Dr. Ho) and second author (Dr. Chen) are contributed equally to this work. They are the co-first authors.
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Ho, BL., Chen, CF., Lin, RT. et al. Clinical implication of hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator. Neurol Sci 37, 1799–1805 (2016). https://doi.org/10.1007/s10072-016-2667-x
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DOI: https://doi.org/10.1007/s10072-016-2667-x