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Long-Term Outcomes of Post-Thrombolytic Intracerebral Hemorrhage in Ischemic Stroke Patients

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Abstract

Background

Intracerebral hemorrhage (ICH) is an infrequent complication of intravenous recombinant tissue plasminogen activator (rt-PA) for the treatment of acute stroke. However, such ICH is an important reason for withdrawal of care because of lack of adequate data regarding long-term patient outcomes.

Objective

To report the long-term outcomes in patients with post-thrombolytic ICH.

Methods

We analyzed patient data from a randomized, placebo-controlled trial in patients with ischemic stroke presenting within 3 h of symptom onset. Baseline clinical characteristics and outcomes defined by modified Rankin scale (mRS) were ascertained at 3, 6, and 12 months after treatment in patients who suffered from post-thrombolytic ICH. Favorable outcome was defined by mRS of 0–3 and unfavorable outcome by mRS of 4–6 at 1 year.

Results

A total of 48 patients suffered post-thrombolytic ICH in the trial. Fourteen patients had favorable outcomes and 34 patients had unfavorable outcomes. Clinical characteristics did not have an impact on patient outcomes at 12 months. Patients with unfavorable outcomes were more likely to have an National Institutes of Health Stroke Scale (NIHSS) score ≥20 at 7–10 days after treatment (64 vs. 7 %, p < 0.0009). Patients with unfavorable outcomes were more likely to have a worsening of NIHSS score of >4 points at 7–10 days from their baseline NIHSS (44 vs. 0 %, p = 0.0006).

Conclusion

Approximately 30 % of patients with post-thrombolytic ICH have favorable outcomes at 1 year which does not support early withdrawal of care. Ascertainment of NIHSS score and worsening of NIHSS score at 7–10 days may be necessary for accurate prognostic stratification.

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References

  1. Adams H, Adams R, Del Zoppo G, et al. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005;36(4):916–23.

    Article  PubMed  Google Scholar 

  2. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004;126(3 Suppl):483S–512S.

    Google Scholar 

  3. The National Institute of Neurological Disorders, Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581–7.

    Article  Google Scholar 

  4. Qureshi AI, Chaudhry SA, Rodriguez GJ, et al. Outcome of the ‘drip-and-ship’ paradigm among patients with acute ischemic stroke: results of a statewide study. Cerebrovasc Dis Extra. 2012;2(1):1–8.

    Article  PubMed  Google Scholar 

  5. Wardlaw JM, Murray V, Berge E, et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2009;(4):CD000213.

  6. Clark WM, Wissman S, Albers GW, et al. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA. 1999;282(21):2019–26.

    Article  PubMed  CAS  Google Scholar 

  7. Hacke W, Kaste M, Fieschi C, et al. Randomised 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. 1998;352(9136):1245–51.

    Article  PubMed  CAS  Google Scholar 

  8. Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363(9411):768–74.

    Article  PubMed  Google Scholar 

  9. Lansberg MG, Albers GW, Wijman CA. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors. Cerebrovasc Dis. 2007;24(1):1–10.

    Article  PubMed  Google Scholar 

  10. Libman R, Kwiakowski T, Lyden P, et al. Asymptomatic hemorrhagic transformation of cerebral infarction does not worsen long-term outcome. J Stroke Cerebrovasc Dis. 2005;14(2):50–4.

    Article  PubMed  Google Scholar 

  11. Zahuranec DB, Brown DL, Lisabeth LD, et al. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology. 2007;68(20):1651–7.

    Article  PubMed  CAS  Google Scholar 

  12. Saver JL. Hemorrhage after thrombolytic therapy for stroke: the clinically relevant number needed to harm. Stroke. 2007;38(8):2279–83.

    Article  PubMed  CAS  Google Scholar 

  13. Kwiatkowski TG, Libman RB, Frankel M, et al. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group. N Engl J Med. 1999;340(23):1781–7.

    Article  PubMed  CAS  Google Scholar 

  14. Patel SC, Levine SR, Tilley BC, et al. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. JAMA. 2001;286(22):2830–8.

    Article  PubMed  CAS  Google Scholar 

  15. Qureshi AI, Chaudhry SA, Sapkota BL, et al. Discharge destination as a surrogate for modified rankin scale defined outcomes at 3- and 12-months poststroke among stroke survivors. Arch Phys Med Rehabil. 2012;93(8):1408–13.

    Article  PubMed  Google Scholar 

  16. Barber PA, Demchuk AM, Zhang J, et al. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta stroke programme early CT score. Lancet. 2000;355(9216):1670–4.

    Article  PubMed  CAS  Google Scholar 

  17. The NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke. 1997;28(11):2109–18.

    Article  Google Scholar 

  18. Barch C, Spilker J, Bratina P, et al. Nursing management of acute complications following rt-PA in acute ischemic stroke. The NINDS rt-PA Stroke Study Group. J Neurosci Nurs. 1997;29(6):367–72.

    Article  PubMed  CAS  Google Scholar 

  19. Sulter G, Steen C, De Keyser J. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke. 1999;30(8):1538–41.

    Article  PubMed  CAS  Google Scholar 

  20. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J. 1965;14:61–5.

    PubMed  CAS  Google Scholar 

  21. Dhamoon MS, Moon YP, Paik MC, et al. Long-term functional recovery after first ischemic stroke: the Northern Manhattan Study. Stroke. 2009;40(8):2805–11.

    Article  PubMed  Google Scholar 

  22. Donnan G, Davis S. ASK trial: predictors of good outcome. Cerebrovasc Dis. 1996;6:183.

    Article  Google Scholar 

  23. Morris AD, Ritchie C, Grosset DG, et al. A pilot study of streptokinase for acute cerebral infarction. QJM. 1995;88(10):727–31.

    PubMed  CAS  Google Scholar 

  24. del Zoppo GJ, von Kummer R, Hamann GF. Ischaemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke. J Neurol Neurosurg Psychiatry. 1998;65(1):1–9.

    Article  PubMed  Google Scholar 

  25. Del Zoppo GJ, Zeumer H, Harker LA. Thrombolytic therapy in stroke: possibilities and hazards. Stroke. 1986;17(4):595–607.

    Article  PubMed  Google Scholar 

  26. Rosenberg GA, Estrada EY, Dencoff JE. Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke. 1998;29(10):2189–95.

    Article  PubMed  CAS  Google Scholar 

  27. Montaner J, Alvarez-Sabín J, Molina C, et al. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke. 2001;32(8):1759–66.

    Article  PubMed  CAS  Google Scholar 

  28. Heo JH, Lucero J, Abumiya T, et al. Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. J Cereb Blood Flow Metab. 1999;19(6):624–33.

    Article  PubMed  CAS  Google Scholar 

  29. Molina CA, Montaner J, Abilleira S, et al. Time course of tissue plasminogen activator-induced recanalization in acute cardioembolic stroke: a case–control study. Stroke. 2001;32(12):2821–7.

    Article  PubMed  CAS  Google Scholar 

  30. Fisher M, Adams RD. Observations on brain embolism with special reference to the mechanism of hemorrhagic infarction. J Neuropathol Exp Neurol. 1951;10(1):92–4.

    PubMed  CAS  Google Scholar 

  31. Ogata J, Yutani C, Imakita M, et al. Hemorrhagic infarct of the brain without a reopening of the occluded arteries in cardioembolic stroke. Stroke. 1989;20(7):876–83.

    Article  PubMed  CAS  Google Scholar 

  32. Tanne D, Kasner SE, Demchuk AM, et al. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation. 2002;105(14):1679–85.

    Article  PubMed  CAS  Google Scholar 

  33. Larrue V, von Kummer RR, Müller A, et al. 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. 2001;32(2):438–41.

    Article  PubMed  CAS  Google Scholar 

  34. Hill MD, Buchan AM, Investigators CAfSESC. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for stroke effectiveness study. CMAJ. 2005;172(10):1307–12.

    Article  PubMed  Google Scholar 

  35. Kase CS, Furlan AJ, Wechsler LR, et al. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology. 2001;57(9):1603–10.

    Article  PubMed  CAS  Google Scholar 

  36. Dubey N, Bakshi R, Wasay M, et al. Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke. J Neuroimaging. 2001;11(2):184–8.

    Article  PubMed  CAS  Google Scholar 

  37. Gilligan AK, Markus R, Read S, et al. Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke. Stroke. 2002;33(9):2236–42.

    Article  PubMed  CAS  Google Scholar 

  38. Ribo M, Montaner J, Molina CA, et al. Admission fibrinolytic profile is associated with symptomatic hemorrhagic transformation in stroke patients treated with tissue plasminogen activator. Stroke. 2004;35(9):2123–7.

    Article  PubMed  CAS  Google Scholar 

  39. Selim M, Fink JN, Kumar S, et al. Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume. Stroke. 2002;33(8):2047–52.

    Article  PubMed  CAS  Google Scholar 

  40. Fiorelli M, Bastianello S, von Kummer R, et al. 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. 1999;30(11):2280–4.

    Article  PubMed  CAS  Google Scholar 

  41. Berger C, Fiorelli M, Steiner T, et al. Hemorrhagic transformation of ischemic brain tissue: asymptomatic or symptomatic? Stroke. 2001;32(6):1330–5.

    Article  PubMed  CAS  Google Scholar 

  42. Molina CA, Alvarez-Sabín J, Montaner J, et al. Thrombolysis-related hemorrhagic infarction: a marker of early reperfusion, reduced infarct size, and improved outcome in patients with proximal middle cerebral artery occlusion. Stroke. 2002;33(6):1551–6.

    Article  PubMed  Google Scholar 

  43. Gebel JM, Sila CA, Sloan MA, 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. 1998;29(3):563–9.

    Article  PubMed  CAS  Google Scholar 

  44. Brown DL, Barsan WG, Lisabeth LD, et al. Survey of emergency physicians about recombinant tissue plasminogen activator for acute ischemic stroke. Ann Emerg Med. 2005;46(1):56–60.

    Article  PubMed  Google Scholar 

  45. Appelros P, Nydevik I, Viitanen M. Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year. Stroke. 2003;34(1):122–6.

    Article  PubMed  Google Scholar 

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Correspondence to Kiersten E. Norby.

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Norby, K.E., Siddiq, F., Adil, M.M. et al. Long-Term Outcomes of Post-Thrombolytic Intracerebral Hemorrhage in Ischemic Stroke Patients. Neurocrit Care 18, 170–177 (2013). https://doi.org/10.1007/s12028-012-9803-0

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