Predictors of Symptomatic Intracerebral Haemorrhage after Systemic Thrombolysis for Cerebral Infarction

Czech version

Authors: D. Václavík ^1,2; R. Mikulík ³; P. Kadlecová ⁴; M. Bar ²; K. Blejchařová ¹; R. Herzig ⁵; J. Neumann ⁶; O. Škoda ⁷; S. Peška ⁸; P. Ševčík ⁹
Authors‘ workplace: Iktové centrum, neurologické oddělení, Vítkovická nemocnice a. s., Ostrava ¹; Neurologická klinika LF OU a FN Ostrava ²; Mezinárodní centrum klinického výzkumu (ICRC), Neurologická klinika FN u sv. Anny v Brně ³; Mezinárodní centrum klinického výzkumu (ICRC), FN u sv. Anny v Brně ⁴; Komplexní cerebrovaskulární centrum, Neurologická klinika LF UP a FN Olomouc ⁵; Iktové centrum, Krajská zdravotní a. s. – Nemocnice Chomutov, o. z. ⁶; Iktové centrum, Nemocnice Jihlava p. o. ⁷; Komplexní cerebrovaskulární centrum, Neurologická klinika LF MU a FN Brno ⁸; Komplexní cerebrovaskulární centrum, Neurologická klinika LF UK a FN Plzeň ⁹
Published in: Cesk Slov Neurol N 2012; 75/108(6): 715-720
Category: Original Paper

Overview

Background:
Symptomatic intracerebral hemorrhage (SICH) following thrombolytic therapy for stroke is associated with a high rate of morbidity and mortality. The aim of our study was to demonstrate predictive value of SICH for good clinical outcome measured by modified Rankin scale (mRS) and to identify predictors of SICH in patients after systemic thrombolysis in the Czech Republic.

Methods:
Data collected from the SITS registry (Safe Implementation of Treatments in Stroke) of Czech patients treated with intravenous thrombolysis between February 2003 and February 2010 were analyzed with uni- and multivariate regression analysis. The outcome variable was SICH, defined as deterioration in NIHSS ≥ 4 points and intracerebral hemorrhage type 2 within 22–36 hours from the start of thrombolysis.

Results:
A total of 2821 patients with ischemic stroke were treated with intravenous thrombolysis. SICH were observed in 60 (2.1%) patients. Patients with SICH were by 87% less likely to reach mRS 0–1 three months after thee stroke (OR = 0.13; 95% CI 0.04–0.44). The following independent predictors of SICH were identified: baseline NIHSS >12 (OR 0.4; 95% CI 0.25–0.79), glucose (OR 1.1, 95% CI 1.03–1.18), congestive heart failure (OR 2.1; 95% CI 1.1–4.02), hypertension (OR 2.4; 95% CI 1.03–5.81).

Conclusions:
In the Czech Republic, the frequency of symptomatic bleeding after thrombolysis was similar to other countries. SICH significantly worsened prognosis of patients after thrombolysis. Patients with hypertension, higher glucose level, more severe stroke and presence of congestive heart failure were at higher risk of SICH. Our data are useful when stratifying the risk after intravenous thrombolysis.

Key words:
ischemic stroke – systemic thrombolysis – symptomatic intracerebral hemorrhage – predictors

Sources

1. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004; 363(9411): 768–774.

2. Ahmed N, Wahlgren N, Grond M, Hennerici M, Lees KR, Mikulik R et al. SITS Investigators. 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(9): 866–874.

3. Petrovicsová M, Kadlecová P, Václavík D, Šaňák D, Ševčík P, Škoda O et al. Bezpečnost a účinnost intravenózní trombolytické terapie mozkového infarktu u pacientů nad 80 let věku. Cesk Slov Neurol N 2012; 75/108(5): 581–585.

4. Bar M, Kadlecová P, Václavík D, Mikulík R, Neumann J, Škoda O et al. Stanovení prognostických faktorů trombolytické léčby u pacientů s akutním mozkovým infarktem – analýza registru SITS. Cesk Slov Neurol N 2012; 75/108(4): 426–431.

5. Mikulik R, Kadlecova P, Czlonkowska A, Kobayashi A, Brozman M, Svigelj V et al. Factors influencing in-hospital delay in treatment with intravenous thrombolysis. Stroke 2012; 43(6): 1578–1583.

6. Mikulík R, Neumann J, Školoudík D, Václavík D. Standard pro diagnostiku a léčbu pacientů s mozkovým infarktem. Cesk Slov Neurol N 2006; 69/102(4): 320–325.

7. Bluhmki E, Chamorro A, Dávalos A, Machnig T, Sauce C, Wahlgren N et al. Stroke treatment with alteplase given 3.0–4.5 h after onset of acute ischaemic stroke (ECASS III): additional outcomes and subgroup analysis of a randomised controlled trial. Lancet Neurol 2009; 8(12): 1095–1102.

8. Wahlgren N, Ahmed N, Eriksson N, Aichner F, Bluhmki E, Dávalos A et al. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). Stroke 2008; 39(12): 3316–3322.

9. Larrue V, von Kummer RR, Müller A, Bluhmki E. 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): 438–441.

10. 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.

11. Kawai N, Keep RF, Betz AL. Hyperglycemia at the vascular effects of cerebral ischemia. Stroke 1997; 28(1): 149–154.

12. Rodríguez-Yáñez M, Castellanos M, Blanco M, Millán M, Nombela F, Sobrino T et al. Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic stroke. Neurology 2006; 67(7): 1172–1177.

13. Ribo M, Montaner J, Molina CA, Arenillas JF, Santamarina E, Quintana M et al. Admission fibrinolytic profile is associated with symptomatic hemorrhagic transformation in stroke patients treated with tissue plasminogen activator. Stroke 2004; 35(9): 2123–2127.

14. Catto AJ, Kohler HP, Bannan S, Stickland M, Carter A, Grant PJ. Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage. Stroke 1998; 29(4): 813–816.

15. Thomalla G, Schwark C, Sobesky J, Bluhmki E, Fiebach JB, Fiehler J et al. Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials. Stroke 2006; 37(3): 852–858.

16. Singer OC, Humpich MC, Fiehler J, Albers GW, Lansberg MG, Kastrup A et al. Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging. Ann Neurol 2008; 63(1): 52–60.

17. Singer OC, Berkefeld J, Lorenz MW, Fiehler J, Albers GW, Lansberg MG et al. Risk of symptomatic intracerebral hemorrhage in patients treated with intra-arterial thrombolysis. Cerebrovasc Dis 2009; 27(4): 368–374.

18. Saver JL. Heorrhage after thrombolytic therapy for stroke: the clinically relevant number needed to harm. Stroke 2007; 38(8): 2279–2283.

19. Saqqur M, Tsivgoulis G, Molina CA, Demchuk AM, Siddiqui M, Alvarez-Sabín J et al. CLOTBUST Investigators. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology 2008; 71(17): 1304–1312.

20. Palumbo V, Boulanger JM, Hill MD, Inzitari D, Buchan AM. Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke. Neurology 2007; 68(13): 1020–1024.

21. Nafría C, Fernández-Cadenas I, Mendioroz M, Domingues-Montanari S, Hernández-Guillamón M, Fernández-Morales J et al. Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients. Stroke Res Treat 2011; 2011: 182783.

22. Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M 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): 1679–1685.

23. Wahlgren N, Ahmed N, Eriksson N. Aichner F, Bluhmki E, Dávalos A et al. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke – Monitoring Study (SITS-MOST). Stroke 2008; 39(12): 3316–3322.

24. Hill MD, Buchan AM. Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005; 172(10): 1307–1312.

25. Gilligan AK, Markus R, Read S, Srikanth V, Hirano T, Fitt G et al. Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke. Stroke 2002; 33(9): 2236–2242.

26. Mazya M, Egido JA, Ford GA, Lees KR, Mikulik R, Toni D et al. Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: Safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score. Stroke 2012; 43(6): 1524–1531.