Symptomatic Intracerebral Hemorrhage after Intravenous Thrombolysis: Predictive Factors and Validation of Prediction Models.

Thrombolytic therapy with intravenous alteplase (IV-rtPA) has a known risk of symptomatic intracerebral hemorrhage (sICH). We aim to identify factors with a significant association with the development of sICH post-IV-rtPA. We also aim to perform an external validation of sICH predicting scores in our patient population. We performed a retrospective chart review of patients who received IV-rtPA at our tertiary care hospital. We excluded patients who underwent mechanical thrombectomy. We analyzed various factors recorded at presentation such as presenting mean arterial pressure (MAP), blood glucose, National Institutes of Health Stroke Scale (NIHSS) score, verify Aspirin, verify Plavix, age, sex, platelet count, international normalized ratio, prothrombin time, partial thromboplastin time, hemoglobin A1c, low-density lipoprotein, onset to treatment time, weight, sex, and early infarct signs on computed tomography (CT) head and compared them between sICH and non-sICH groups. For validation of sICH scores, we used documented variables to calculate the following scores for each patient: stroke prognostication using age and NIH stroke scale-100 (SPAN-100), DRAGON, CUCCHIARA, hemorrhage after thrombolysis (HAT), SEDAN, totaled health risks in vascular events, and safe implementation of thrombolysis in stroke-symptomatic intracerebral hemorrhage. sICH rate in our cohort of 89 patients was 5.62% according to the European-Australasian Cooperative Acute Stroke Study-II (ECASS-II) criteria and 7.86% according to the National Institute of Neurological Disorders and Stroke (NINDS) criteria. In the multivariate regression analysis, MAP (95% CI, .001-.01; P .002), blood glucose greater than or equal to 185 mg/dL (95% CI, .12-.45; P .001) and presence of early infarct signs (95% CI, .06-.25; P .002) had a significant association with the development of sICH with the ECASS-II definition of sICH post-IV-rtPA, whereas, only MAP (95% CI, 1.01-1.18; P .025) and verify Aspirin less than 500 (95% CI, .01-.80; P .032) had a significant association with the development of sICH with the NINDS definition of sICH post-IV-rtPA. Our study found that HAT (95% CI, .58-.96; P .044) and DRAGON (95% CI, .61-.96; P .012) scores had the highest area under the curve (AUC) with respect to ECASS-II and NINDS criteria of sICH, respectively. We found that presenting MAP, presence of early infarct signs on CT Head and blood glucose greater than or equal to 185 mg/dL upon a patient's presentation have a significant association with sICH post-IV-rtPA when the ECASS-II definition was used, while presenting MAP and verify Aspirin less than 500 upon a patient's presentation have a significant association with sICH post-IV-rtPA when the NINDS definition was used. Our study found that HAT and DRAGON scores had the highest AUC, and they were the most valid in predicting the development of sICH in our independent cohort. Patients with these risk factors should receive more intensive neurological monitoring.

Nisar T ，Hanumanthu R ，Khandelwal P 《-》

Symptomatic intracerebral hemorrhage after intravenous thrombolysis in Chinese patients: comparison of prediction models.

To assess the performance of risk scores in predicting symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT). A multicenter prospective study was performed in 811 patients who underwent IVT with standard-dose recombinant tissue plasminogen activator within 4.5 hours of acute ischemic stroke (AIS) onset in 67 stroke centers involved in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China program from May 2007 to April 2012. SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age) score, Safe Implementation of Thrombolysis in Stroke (SITS)-SICH score, Glucose Race Age Sex Pressure Stroke Severity (GRASPS) score, Multicenter Stroke Survey (MSS) score, and Stroke Prognostication using Age and National Institutes of Health Stroke Scale (SPAN)-100 index were calculated in selected patients, and their predictive performance for SICH was compared according to the National Institute of Neurological Disorders and Stroke (NINDS), Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), and European Cooperative Acute Stroke Study (ECASS)-II criteria. For predicting the risk of SICH (NINDS definition) after IVT, the area under the receiver operating characteristic (ROC) curve of MSS score was the highest (.71, P < .0001). For predicting the risk of SICH (SITS-MOST definition) after IVT, the area under the ROC curve of GRASPS score was the highest (.73, P = .005). For predicting SICH (ECASS-II definition) after IVT, the area under the ROC curve of MSS score was the highest (.73, P < .0001). SITS-SICH, GRASPS, and MSS scores predicted the risk of SICH after IVT in patients with AIS, but only the latter 2 were better in the Chinese population. MSS score had the best predictive performance for SICH using NINDS and ECASS-II definitions, whereas GRASPS score was the best for SICH using the SITS-MOST definition.

Li M ，Wang-Qin RQ ，Wang YL ，Liu LB ，Pan YS ，Liao XL ，Wang YJ ，Xu AD ... -  《-》

Comparison of risk-scoring systems in predicting symptomatic intracerebral hemorrhage after intravenous thrombolysis.

Sung SF ，Chen SC ，Lin HJ ，Chen YW ，Tseng MC ，Chen CH ... -  《-》

The THRIVE score predicts symptomatic intracerebral hemorrhage after intravenous tPA administration in SITS-MOST.

The Totaled Health Risks in Vascular Events (THRIVE) score is a clinical prediction score that predicts ischemic stroke outcomes in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute therapy. We have previously found an association between THRIVE and risk of post-tissue plasminogen activator symptomatic intracranial hemorrhage in the National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator trial and risk of radiographic hemorrhage in Virtual International Stroke Trials Archive. The study aims to validate the relationship between THRIVE and symptomatic intracranial hemorrhage among tissue plasminogen activator-treated patients in the large Safe Implementation of Thrombolysis in Stroke - Monitoring Study (SITS-MOST). This is a retrospective analysis of the prospective SITS-MOST to examine the relationship between THRIVE and symptomatic intracranial hemorrhage after tissue plasminogen activator treatment. Symptomatic intracranial hemorrhage after tissue plasminogen activator was defined according to each of three standard definitions: the NINDS, European Cooperative Acute Stroke Study (ECASS), and Safe Implementation of Thrombolysis in Stroke (SITS) criteria. Multivariable logistic regression was used to confirm the relationship of THRIVE and individual THRIVE components with the risk of symptomatic intracranial hemorrhage and to examine the relationship of THRIVE, symptomatic intracranial hemorrhage, and functional outcome. The odds ratio for symptomatic intracranial hemorrhage at each increased level of THRIVE score is 1·34 (95% CI 1·27 to 1·41, P < 0·001) for symptomatic intracranial hemorrhage by NINDS criteria, 1·36 (95% CI 1·27 to 1·46, P < 0·001) for symptomatic intracranial hemorrhage by ECASS criteria, and 1·21 (95% CI 1·09 to 1·36, P < 0·001) for symptomatic intracranial hemorrhage by SITS criteria. In receiver-operator characteristics analysis, the C-statistic for THRIVE prediction of symptomatic intracranial hemorrhage was 0·65 (95% CI 0·62 to 0·67) for symptomatic intracranial hemorrhage by NINDS criteria, 0·66 (95% CI 0·63 to 0·69) for symptomatic intracranial hemorrhage by ECASS criteria, and 0·61 (95% CI 0·56 to 0·66) for symptomatic intracranial hemorrhage by SITS criteria. Each component of the THRIVE score predicts the risk of symptomatic intracranial hemorrhage, with independent impact of each component in multivariable analysis. The THRIVE score predicts the risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator administration. This external validation of the relationship between THRIVE and symptomatic intracranial hemorrhage in a prospective study further strengthens the role of the THRIVE score in the prediction of poststroke outcomes.

Flint AC ，Gupta R ，Smith WS ，Kamel H ，Faigeles BS ，Cullen SP ，Rao VA ，Bath PM ，Wahlgren N ，Ahmed N ，Donnan GA ，SITS International and VISTA-plus investigators ... -  《-》

Renal Dysfunction Associated with Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis.

Renal dysfunction (RD) is prevalent in patients with acute ischemic stroke requiring intravenous thrombolysis. The relationship between renal function and thrombolysis related intracranial hemorrhagic (ICH) complications is contradictory according to previous studies. The current study is to clarify whether RD could increase the risk of symptomatic intracranial hemorrhage (SICH) after recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke patients. In this observational study, acute ischemic stroke patients who received IV rtPA within 4.5 hours of symptom onset were retrospectively analyzed. Creatinine levels on admission served to calculate glomerular filtration rate (GFR) to estimate RD. SICH was defined with National Institute of Neurological Disorder and Stroke (NINDS, SICHNINDS) or European Cooperative Acute Stroke Study II (ECASS II, SICHECASSII) criteria. Association of RD with SICH was assessed using continuous GFR or binary GFR (RD defined as GFR < 90 ml/minute/1.73 m2). Of 312 patients included, the incidence of SICHNINDS was 7.69%, of SICHECASSII was 5.45%. Patients with RD had higher prevalence of SICHNINDS (12.80% versus 2.03%, P < .001) and SICHECASS II (9.15% versus 1.35%, P = .002). GFR as a continuous variable was associated with SICHNINDS (ORadjust = .97, P = .003), but not with SICHECASS II. GFR less than 90 ml/minute/1.73 m2 remained independently associated with SICHNINDS (ORadjust = 4.79, P = .016), and SICHECASS II (ORadjust = 2.99, P = .032) in multiple logistic regression analysis. Renal function is independently associated with SICH after IV rtPA thrombolysis. RD is an independent predictor for both SICHNINDS and SICHECASS II. RD should be considered when evaluating the risk of intravenous thrombolysis with IV rtPA.

Zhu J ，Shen X ，Han C ，Mei C ，Zhou Y ，Wang H ，Kong Y ，Jiang Y ，Fang Q ，Cai X ... -  《-》