Should we exclude acute stroke patients with previous intracerebral hemorrhage from receiving intravenous thrombolysis?

Abstract

Background

Current guidelines have contraindicated history of intracerebral hemorrhage for intravenous recombinant tissue plasminogen activator.

Aim

This study aimed to investigate the safety and effectiveness of intravenous recombinant tissue plasminogen activator for patients who had previous intracerebral hemorrhage on history or initial brain magnetic resonance imaging.

Methods

Using a prospective multicenter stroke registry database, we identified acute ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator within 4.5 h of onset. Previous intracerebral hemorrhage was defined as having a clinical history or evidence of old intracerebral hemorrhage on initial brain magnetic resonance imaging. Associations of previous intracerebral hemorrhage with symptomatic hemorrhagic transformation during hospitalization and functional outcome and mortality at discharge and three months were analyzed.

Results

Among 1495 patients who were treated with intravenous recombinant tissue plasminogen activator, 73 (4.9%) had previous intracerebral hemorrhage; 9 on history only, 61 on magnetic resonance imaging only and 3 on both. Of those 1495 patients, 71 (4.7%) experienced symptomatic hemorrhagic transformation; 6.8% in patients with previous intracerebral hemorrhage and 4.6% in those without previous intracerebral hemorrhage. Multivariable logistic regression analysis showed that previous intracerebral hemorrhage did not significantly increase the risk of symptomatic hemorrhagic transformation (odds ratio 1.08, 95% confidence interval 0.39–2.96) mortality, and most of functional outcome measures

Conclusions

Previous intracerebral hemorrhage may neither increase the risk of symptomatic hemorrhagic transformation nor alter major clinical outcomes in acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator. This study suggests reconsideration of prior history of intracerebral hemorrhage as an exclusion criterion for intravenous recombinant tissue plasminogen activator administration in acute ischemic stroke.

Keywords

Acute ischemic stroke history of intracerebral hemorrhage brain macrobleed intravenous thrombolysis symptomatic hemorrhagic transformation mortality

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References

Jauch

Saver

Adams

Jr . Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44: 870–947.

Green

. Canadian stroke best practices update 2010. Can J Neurosci Nurs 2011; 33: 4–5.

Schellinger

Ringleb

Hacke

. European Stroke Organisation 2008 guidelines for managing acute cerebral infarction or transient ischemic attack: part 2. Der Nervenarzt 2008; 79: 1180–1184, 6–8, 90–201.

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333: 1581–1587.

Brott TG, Haley Jr EC, Levy D, et al. Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992; 23: 632–640.

Haley Jr EC, Levy, DE, Brott T, et al. Urgent therapy for stroke. Part II. Pilot study of tissue plasminogen activator administered 91-180 minutes from onset. Stroke 1992; 23: 641–645.

Tong D. Are all IV thrombolysis exclusion criteria necessary? Being SMART about evidence-based medicine. Neurology 2011; 76: 1780–1781.

Aoki

Shibazaki

Saji

Uemura

Sakamoto

Kimura

. Risk of intracerebral hemorrhage after thrombolysis in patients with asymptomatic hemorrhage on T2*. Cerebrovasc Dis 2014; 38: 107–116.

Kidwell

Wintermark

. Imaging of intracranial haemorrhage. Lancet Neurol 2008; 7: 256–267.

10.

Kim

Han

Park

. Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry. Int J Stroke 2014; 9: 514–518.

11.

Lee

Chung

. MRI-based algorithm for acute ischemic stroke subtype classification. J Stroke 2014; 16: 161–172.

12.

Roob

Lechner

Schmidt

Flooh

Hartung

Fazekas

. Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000; 31: 2665–2669.

13.

Kothari

Brott

Broderick

. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996; 27: 1304–1305.

14.

Wahlgren

Ahmed

Davalos

. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369: 275–282.

15.

Kim

Park

Kang

. Case characteristics, hyperacute treatment, and outcome information from the clinical research center for stroke – fifth division registry in South Korea. J Stroke 2015; 17: 38–53.

16.

Seet

Rabinstein

. Symptomatic intracranial hemorrhage following intravenous thrombolysis for acute ischemic stroke: a critical review of case definitions. Cerebrovasc Dis 2012; 34: 106–114.

17.

Aleu

Mellado

Lichy

Kohrmann

Schellinger

. Hemorrhagic complications after off-label thrombolysis for ischemic stroke. Stroke 2007; 38: 417–422.

18.

Tanne

Kasner

Demchuk

. 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: 1679–1685.

19.

Ahmed

Wahlgren

Grond

. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol 2010; 9: 866–874.

20.

Fonarow

Smith

Saver

. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation 2011; 123: 750–758.

21.

Nadeau

Shi

Fang

. TPA use for stroke in the registry of the Canadian Stroke Network. Can J Neurol Sci 2005; 32: 433–439.

22.

Pantoni

. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689–701.

23.

Sussman

Connolly

Jr . Hemorrhagic transformation: a review of the rate of hemorrhage in the major clinical trials of acute ischemic stroke. Front Neurol 2013; 4: 69.

24.

Mozaffarian

Benjamin

. Heart disease and stroke statistics – 2015 update: a report from the American Heart Association. Circulation 2015; 131: e29–e322.

25.

Kleindorfer

Kissela

Schneider

. Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study. Stroke 2004; 35: e27–e29.

26.

de Los Rios la Rosa

Khoury

Kissela

. Eligibility for intravenous recombinant tissue-type plasminogen activator within a population: the effect of the European Cooperative Acute Stroke Study (ECASS) III trial. Stroke 2012; 43: 1591–1595.