Skip to main content
Top
Published in: BMC Neurology 1/2020

Open Access 01-12-2020 | Cerebral Small Vessel Disease | Research article

A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients

Authors: Yaya Wu, Hui Chen, Xueyun Liu, Xiuying Cai, Yan Kong, Hui Wang, Yun Zhou, Juehua Zhu, Lulu Zhang, Qi Fang, Tan Li

Published in: BMC Neurology | Issue 1/2020

Login to get access

Abstract

Background

A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA).

Methods

We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell’s concordance index (C-index) and calibration plot.

Results

A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score ≥ 13, and onset-to-treatment time (OTT) ≥ 180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221–0.9904, P < 0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores.

Conclusions

This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score ≥ 13, and OTT ≥ 180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–418.CrossRef Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–418.CrossRef
2.
go back to reference Wardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;(7):CD000213. Wardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;(7):CD000213.
3.
go back to reference Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12(5):483–97.CrossRef Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12(5):483–97.CrossRef
4.
go back to reference Charidimou A, Pasi M, Fiorelli M, Shams S, von Kummer R, Pantoni L, et al. Leukoaraiosis, cerebral hemorrhage, and outcome after intravenous thrombolysis for acute ischemic stroke: a meta-analysis (v1). Stroke. 2016;47(9):2364–72.CrossRef Charidimou A, Pasi M, Fiorelli M, Shams S, von Kummer R, Pantoni L, et al. Leukoaraiosis, cerebral hemorrhage, and outcome after intravenous thrombolysis for acute ischemic stroke: a meta-analysis (v1). Stroke. 2016;47(9):2364–72.CrossRef
5.
go back to reference Zand R, Tsivgoulis G, Singh M, McCormack M, Goyal N, Ishfaq MF, et al. Cerebral microbleeds and risk of intracerebral hemorrhage post intravenous thrombolysis. J Stroke Cerebrovasc Dis. 2017;26(3):538–44.CrossRef Zand R, Tsivgoulis G, Singh M, McCormack M, Goyal N, Ishfaq MF, et al. Cerebral microbleeds and risk of intracerebral hemorrhage post intravenous thrombolysis. J Stroke Cerebrovasc Dis. 2017;26(3):538–44.CrossRef
6.
go back to reference Staals J, Booth T, Morris Z, Bastin ME, Gow AJ, Corley J, et al. Total MRI load of cerebral small vessel disease and cognitive ability in older people. Neurobiol Aging. 2015;36(10):2806–11.CrossRef Staals J, Booth T, Morris Z, Bastin ME, Gow AJ, Corley J, et al. Total MRI load of cerebral small vessel disease and cognitive ability in older people. Neurobiol Aging. 2015;36(10):2806–11.CrossRef
7.
go back to reference Pico F, Labreuche J, Touboul PJ, Leys D, Amarenco P. Intracranial arterial dolichoectasia and small-vessel disease in stroke patients. Ann Neurol. 2005;57(4):472–9.CrossRef Pico F, Labreuche J, Touboul PJ, Leys D, Amarenco P. Intracranial arterial dolichoectasia and small-vessel disease in stroke patients. Ann Neurol. 2005;57(4):472–9.CrossRef
8.
go back to reference Brenner D, Labreuche J, Pico F, Scheltens P, Poirier O, Cambien F, et al. The renin-angiotensin-aldosterone system in cerebral small vessel disease. J Neurol. 2008;255(7):993–1000.CrossRef Brenner D, Labreuche J, Pico F, Scheltens P, Poirier O, Cambien F, et al. The renin-angiotensin-aldosterone system in cerebral small vessel disease. J Neurol. 2008;255(7):993–1000.CrossRef
9.
go back to reference Lou M, Safdar A, Mehdiratta M, Kumar S, Schlaug G, Caplan L, et al. The HAT score: a simple grading scale for predicting hemorrhage after thrombolysis. Neurology. 2008;71(18):1417–23.CrossRef Lou M, Safdar A, Mehdiratta M, Kumar S, Schlaug G, Caplan L, et al. The HAT score: a simple grading scale for predicting hemorrhage after thrombolysis. Neurology. 2008;71(18):1417–23.CrossRef
10.
go back to reference Saposnik G, Guzik AK, Reeves M, Ovbiagele B, Johnston SC. Stroke prognostication using age and NIH stroke scale: SPAN-100. Neurology. 2013;80(1):21–8.CrossRef Saposnik G, Guzik AK, Reeves M, Ovbiagele B, Johnston SC. Stroke prognostication using age and NIH stroke scale: SPAN-100. Neurology. 2013;80(1):21–8.CrossRef
11.
go back to reference Strbian D, Engelter S, Michel P, Meretoja A, Sekoranja L, Ahlhelm FJ, et al. Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score. Ann Neurol. 2012;71(5):634–41.CrossRef Strbian D, Engelter S, Michel P, Meretoja A, Sekoranja L, Ahlhelm FJ, et al. Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score. Ann Neurol. 2012;71(5):634–41.CrossRef
12.
go back to reference Flint AC, Faigeles BS, Cullen SP, Kamel H, Rao VA, Gupta R, et al. THRIVE score predicts ischemic stroke outcomes and thrombolytic hemorrhage risk in VISTA. Stroke. 2013;44(12):3365–9.CrossRef Flint AC, Faigeles BS, Cullen SP, Kamel H, Rao VA, Gupta R, et al. THRIVE score predicts ischemic stroke outcomes and thrombolytic hemorrhage risk in VISTA. Stroke. 2013;44(12):3365–9.CrossRef
13.
go back to reference Menon BK, Saver JL, Prabhakaran S, Reeves M, Liang L, Olson DM, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke. 2012;43(9):2293–9.CrossRef Menon BK, Saver JL, Prabhakaran S, Reeves M, Liang L, Olson DM, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke. 2012;43(9):2293–9.CrossRef
14.
go back to reference 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):1524–31.CrossRef 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):1524–31.CrossRef
15.
go back to reference Jehi L, Yardi R, Chagin K, Tassi L, Russo GL, Worrell G, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283–90.CrossRef Jehi L, Yardi R, Chagin K, Tassi L, Russo GL, Worrell G, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283–90.CrossRef
16.
go back to reference Cappellari M, Turcato G, Forlivesi S, Zivelonghi C, Bovi P, Bonetti B, et al. STARTING-SICH nomogram to predict symptomatic intracerebral hemorrhage after intravenous thrombolysis for stroke. Stroke. 2018;49(2):397–404.CrossRef Cappellari M, Turcato G, Forlivesi S, Zivelonghi C, Bovi P, Bonetti B, et al. STARTING-SICH nomogram to predict symptomatic intracerebral hemorrhage after intravenous thrombolysis for stroke. Stroke. 2018;49(2):397–404.CrossRef
17.
go back to reference Cappellari M, Mangiafico S, Saia V, Pracucci G, Nappini S, Nencini P, et al. IER-SICH nomogram to predict symptomatic intracerebral hemorrhage after thrombectomy for stroke. Stroke. 2019;50(4):909–16.CrossRef Cappellari M, Mangiafico S, Saia V, Pracucci G, Nappini S, Nencini P, et al. IER-SICH nomogram to predict symptomatic intracerebral hemorrhage after thrombectomy for stroke. Stroke. 2019;50(4):909–16.CrossRef
18.
go back to reference Larrue V, von Kummer RR, Muller 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):438–41.CrossRef Larrue V, von Kummer RR, Muller 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):438–41.CrossRef
19.
go back to reference Nguyen-Huynh MN, Klingman JG, Avins AL, Rao VA, Eaton A, Bhopale S, et al. Novel telestroke program improves thrombolysis for acute stroke across 21 hospitals of an integrated healthcare system. Stroke. 2018;49(1):133–9.CrossRef Nguyen-Huynh MN, Klingman JG, Avins AL, Rao VA, Eaton A, Bhopale S, et al. Novel telestroke program improves thrombolysis for acute stroke across 21 hospitals of an integrated healthcare system. Stroke. 2018;49(1):133–9.CrossRef
20.
go back to reference Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987;149(2):351–6.CrossRef Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987;149(2):351–6.CrossRef
21.
go back to reference Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41(3):450–4.CrossRef Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41(3):450–4.CrossRef
22.
go back to reference Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38.CrossRef Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38.CrossRef
23.
go back to reference Huijts M, Duits A, van Oostenbrugge RJ, Kroon AA, de Leeuw PW, Staals J. Accumulation of MRI markers of cerebral small vessel disease is associated with decreased cognitive function. A study in first-ever lacunar stroke and hypertensive patients. Front Aging Neurosci. 2013;5:72.CrossRef Huijts M, Duits A, van Oostenbrugge RJ, Kroon AA, de Leeuw PW, Staals J. Accumulation of MRI markers of cerebral small vessel disease is associated with decreased cognitive function. A study in first-ever lacunar stroke and hypertensive patients. Front Aging Neurosci. 2013;5:72.CrossRef
24.
go back to reference Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83(14):1228–34.CrossRef Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83(14):1228–34.CrossRef
25.
go back to reference Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J. Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke. 2013;44(11):2995–9.CrossRef Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J. Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke. 2013;44(11):2995–9.CrossRef
26.
go back to reference Alba AC, Agoritsas T, Walsh M, Hanna S, Iorio A, Devereaux PJ, et al. Discrimination and calibration of clinical prediction models: users’ guides to the medical literature. JAMA. 2017;318(14):1377–84.CrossRef Alba AC, Agoritsas T, Walsh M, Hanna S, Iorio A, Devereaux PJ, et al. Discrimination and calibration of clinical prediction models: users’ guides to the medical literature. JAMA. 2017;318(14):1377–84.CrossRef
27.
go back to reference Balachandran VP, Gonen M, Smith JJ, DeMatteo RP. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015;16(4):e173–80.CrossRef Balachandran VP, Gonen M, Smith JJ, DeMatteo RP. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015;16(4):e173–80.CrossRef
28.
go back to reference Arba F, Inzitari D, Ali M, Warach SJ, Luby M, Lees KR, et al. Small vessel disease and clinical outcomes after IV rt-PA treatment. Acta Neurol Scand. 2017;136(1):72–7.CrossRef Arba F, Inzitari D, Ali M, Warach SJ, Luby M, Lees KR, et al. Small vessel disease and clinical outcomes after IV rt-PA treatment. Acta Neurol Scand. 2017;136(1):72–7.CrossRef
29.
go back to reference Lau KK, Li L, Schulz U, Simoni M, Chan KH, Ho SL, et al. Total small vessel disease score and risk of recurrent stroke: validation in 2 large cohorts. Neurology. 2017;88(24):2260–7.CrossRef Lau KK, Li L, Schulz U, Simoni M, Chan KH, Ho SL, et al. Total small vessel disease score and risk of recurrent stroke: validation in 2 large cohorts. Neurology. 2017;88(24):2260–7.CrossRef
30.
go back to reference Liu X, Li T, Diao S, Cai X, Kong Y, Zhang L, et al. The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment. Neurol Sci. 2019;40(6):1157–66.CrossRef Liu X, Li T, Diao S, Cai X, Kong Y, Zhang L, et al. The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment. Neurol Sci. 2019;40(6):1157–66.CrossRef
Metadata
Title
A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients
Authors
Yaya Wu
Hui Chen
Xueyun Liu
Xiuying Cai
Yan Kong
Hui Wang
Yun Zhou
Juehua Zhu
Lulu Zhang
Qi Fang
Tan Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-020-02002-w

Other articles of this Issue 1/2020

BMC Neurology 1/2020 Go to the issue