Post-thrombolysis Intracranial Hemorrhage Research Articles

Risk Factors and a Nomogram for Predicting Intracranial Hemorrhage in Stroke Patients Undergoing Thrombolysis.

PurposeIdentifying stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. We aimed to develop and evaluate a nomogram for predicting the probability of ICH in acute ischemic stroke patients undergoing thrombolysis.Patients and MethodsA retrospective observational study was conducted using data from 345 patients at a single center. The patients were randomly dichotomized into training (2/3; n=233) and validation (1/3; n=112) sets. A prediction model was developed by using a multivariable logistic regression analysis.ResultsThe nomogram comprised three variables: the presence of atrial fibrillation (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 2.09–11.57), the National Institutes of Health Stroke Scale (NIHSS) score (OR: 1.11, 95% CI: 1.04–1.18) and the glucose level on admission (OR: 1.27, 95% CI: 1.08–1.50). The areas under the receiver operating characteristic curve of the nomogram for the training and validation sets were 0.828 (0.753–0.903) and 0.801 (0.690–0.911), respectively. The Hosmer–Lemeshow test revealed good calibration in both the training and validation sets (P = 0.509 and P = 0.342, respectively). The calibration plot also demonstrated good agreement. A decision curve analysis demonstrated that the nomogram was clinically useful.ConclusionWe developed an easy-to-use nomogram model to predict ICH, and the nomogram may provide risk assessments for subsequent treatment in stroke patients undergoing thrombolysis.

Abstract WP123: Risk Factors and Nomogram to Predict Intracranial Hemorrhage in Stroke Patients Undergoing Thrombolysis

Introduction: Identification of stroke patients at risk of postthrombolysis intracranial hemorrhage (ICH) in the clinical setting is essential. We aimed to develop and evaluate a nomogram for predicting the probability of intracranial hemorrhage (ICH) in acute ischemic stroke patients undergoing thrombolysis. Methods: A retrospective observational study was conducted with 287 participants from a single center (67.2% males, median age 65 years). The patients were randomly divided into a training set (160) and a validation set (127). Univariate and multivariate logistic regression analyses of clinical variables were performed to screen for significant prognostic factors. Nomograph that included significant prognostic variables was formulated to predict ICH. Areas under curve (AUC) of receiver operating characteristic (ROC) and calibration plots were formulated to evaluate the predictive accuracy of the nomograph. Results: A total of 41(14.3%) ICH events occurred. A nomogram was developed to predict ICH based on three variables in the training set: the presence of atrial fibrillation (OR: 4.01, P =0.009), the National Institutes of Health Stroke Scale (NIHSS) score (OR: 1.16, P =0.001) and glucose (OR: 1.37, P =0.006) on admission. The AUC-ROC for the training set was 0.817 (0.730-0.925), and for the validation set was 0.809 (0.710-0.904). Calibration plots showed good consistency between the two sets. Conclusion: We developed an easy-to-use nomogram model based on 3 independently clinical factors to predict ICH. The nomogram could be useful for individualized prediction of ICH in intravenous thrombolysis-treated stroke patients..

Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Alteplase: A Systematic Review of the Available Evidence.

Background and PurposeCurrent guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke.MethodsWe performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase.ResultsWe identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70–84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5–11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122–214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported.ConclusionExperience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.

Multidisciplinary Approach to Decrease In-Hospital Delay for Stroke Thrombolysis.

Background and Purpose Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. Methods We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. Results A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36–57 min) to 20.5 min (IQR 15.8–32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5–212.5 min) to 86.5 min (IQR 67.5–102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). Conclusions SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.

Increased Risk of Post-Thrombolysis Intracranial Hemorrhage in Acute Ischemic Stroke Patients with Leukoaraiosis: A Meta-Analysis.

BackgroundLeukoaraiosis is common in patients with acute ischemic stroke. The results from many studies investigating the association between leukoaraiosis and intracranial hemorrhage after thrombolysis remain conflicting.MethodsA meta-analysis was performed to compare the risk of post-thrombolytic intracranial hemorrhage in patients with and without leukoaraiosis. Relevant reports were identified by searching PubMed, EmBase, Cochrane Library, and ISI Web of Science through December 2015 using a combination of subjective and random terms. Eligible studies that were original articles with a clear definition of leukoaraiosis and intracranial hemorrhage were selected and analyzed. Funnel plots, Egger’s test, and Begg’s test were conducted to assess the publication bias. Sensitivity analysis was also performed to evaluate the influence of each individual study.ResultsEleven trials that enrolled 6912 participants were included. There was a significantly increased risk for acute ischemic stroke patients with leukoaraiosis (odds ratio: 1.89, 95% confidence interval 1.51–2.37, P<0.001). Low heterogeneity and less publication bias was detected among these studies. The results of both computed tomography and magnetic resonance imaging performed on the subgroups of leukoaraiosis were significant. Furthermore, an association between leukoaraiosis and symptomatic intracranial hemorrhage was also confirmed. The odds ratios remained stable with no obvious variations on the sensitivity analysis. The limitations consisted of types of including trials and not matching some baseline variables.ConclusionsThe results of this meta-analysis show that leukoaraiosis approximately doubles the incidence of intracranial hemorrhage after thrombolytic therapy. However, it does not critically affect decision making regarding thrombolysis for patients with acute ischemic stroke. Additional investigations are required.

Preexisting dual antiplatelet treatment increases the risk of post-thrombolysis intracranial hemorrhage in Chinese stroke patients

Objective:Previous studies have shown conflicting results on the use of antiplatelet (AP) agent and its risk of symptomatic intracerebral hemorrhage (sICH) following thrombolysis for acute ischemic stroke. Our study was to explore the safety of intravenous (IV) thrombolysis in Chinese stroke patients who were on AP prior to stroke.Methods:Data were collected from the thrombolysis implementation and monitor of acute ischemic stroke in China (TIMS-China) registry. Symptomatic ICH defined per SITS-MOST (safe implementation of treatments in stroke-monitoring study), ECASS II (second European-Australasian acute stroke study), and NINDS (National Institute of Neurological Disorders and Stroke) criteria, 90-day functional outcome, and 7-day and 90-day mortalities were compared between the stroke patients who were on mono and dual AP therapy.Results:A total of 157 (14·2%) patients received at least one AP drug within 24 hours before thrombolysis. Patients with preexisting dual AP treatment had higher rate of sICH (14·3% (2/14) per SITS-MOST, 21·4% (3/14) per ECASS II definitions) than those on no AP treatment. No significant difference was found in the rate of sICH or 7-day or 90-day mortalities between the groups on aspirin (ASA) alone and on no AP treatment.Discussion:The risk of developing sICH is low when thrombolysis is given to patients who are on ASA alone. However, there is potential increased risk of sICH if a patient is on dual AP treatment.

Does Preexisting Antiplatelet Treatment Influence Postthrombolysis Intracranial Hemorrhage in Community‐treated Ischemic Stroke Patients? An Observational Study

Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster-randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques. There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (± 15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = -1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = -1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with preexisting antiplatelet use.

Postthrombolysis Intracranial Hemorrhage Risk of Cerebral Microbleeds in Acute Stroke Patients: A Systematic Review and Meta-Analysis

It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I(2) = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I(2) = 0%] reaching borderline significance (P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage (P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of cerebral microbleed presence.

Is it Post-Thrombolysis Intracranial Hemorrhage?

Intracranial hemorrhage is the commonest cause of hyperdensity on the non-contrast brain CT after thrombolysis with IV-TPA. This may range from minor petechial spots within the infarcted tissue to an extensive parenchymal hematoma. We present a patient who showed considerable clinical recovery after intravenous thrombolysis for acute ischemic stroke. However, his post-thrombolysis CT scan of the brain revealed a discrete hyperdensity in the infarcted region, due to extravasation of radio-contrast injected for CT angiography. His underlying end-stage renal failure probably contributed to a reduced rate of clearance of the contrast from his body. doi:10.4021/jnr83w

Abstract 3092: Does Pre-existing Antiplatelet Treatment Influence Post-thrombolysis Intracranial Hemorrhage In Community Treated Ischemic Stroke Patients?

Background: Post-thrombolysis ICH is associated with poor outcomes. Previous investigations have attempted to determine the relationship between pre-existing anti-platelet (AP) use and the safety of intravenous thrombolysis, but have been limited by low event rates thus decreasing the precision of estimates. Our objective was to determine whether pre-existing AP therapy increases the risk of ICH following thrombolysis. Methods: Consecutive cases of ED treated thrombolysis patients were identified using multiple methods, including active and passive surveillance. Retrospective data were collected from 4 hospitals from 1996-2005, and 24 distinct hospitals from 2007-2010 as part of a cluster randomized trial. The same chart abstraction tool was used during both time periods and data was subjected to numerous quality control checks. Hemorrhages were classified using a pre-specified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow up imaging (primary outcome). Symptomatic ICH (secondary outcome) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to post-thrombolysis ICH. The models included: pre-existing AP use, age*, NIHSS*, pre-treatment systolic blood pressure, onset to treatment interval, pre-treatment blood glucose*, tobacco use, presence of post-treatment protocol violations (*variable classified by quartile). As there were fewer SICH events, the multivariable model was constructed similarly, except that variables divided into quartiles in the primary analysis were dichotomized at the median. Results: There were 830 patients included, with 47% having documented pre-existing AP treatment. The mean age was 69 years, the cohort was 53% male, and the median NIHSS was 12. The unadjusted proportion of patients with any ICH was 15.1% without AP and 19.3% with AP (difference 4.2% [95% CI: -1.2% - 9.6%]); for SICH this was 6.1% without AP and 9% with AP (difference 3.1% [95%CI: -1-6.7%]). No significant association between pre-existing AP treatment with radiographic or symptomatic ICH was observed ( table ). Conclusions: We did not find that AP treatment was associated with post-thrombolysis ICH or SICH in this cohort of community treated patients. Pre-existing tobacco use, younger age, and lower severity were associated with lower odds of SICH. An association between AP therapy and SICH may still exist - further research with larger sample sizes is warranted in order to detect smaller effect sizes.

Is it Post-Thrombolysis Intracranial Hemorrhage?

Intracranial hemorrhage is the commonest cause of hyperdensity on the non-contrast brain CT after thrombolysis with IV-TPA. This may range from minor petechial spots within the infarcted tissue to an extensive parenchymal hematoma. We present a patient who showed considerable clinical recovery after intravenous thrombolysis for acute ischemic stroke. However, his post-thrombolysis CT scan of the brain revealed a discrete hyperdensity in the infarcted region, due to extravasation of radio-contrast injected for CT angiography. His underlying end-stage renal failure probably contributed to a reduced rate of clearance of the contrast from his body. J Neurol Res. 2012;2(1):30-32 doi: https://doi.org/10.4021/jnr83w

Acute Ischemic Stroke and Thrombolysis Location: Comparing Telemedicine and Stroke Center Treatment Outcomes

Background: Telemedicine has been increasingly used as an option for acute ischemic stroke treatment at hospitals where neurological expertise is not available. The aim of this study was to compare the outcome of stroke patients treated with systemic thrombolysis at our academic hub regional stroke centers (hub) versus our spoke hospital telemedicine locations (spoke). Methods: Data were retrospectively reviewed for consecutive patients admitted for stroke treatment with intravenous tissue plasminogen activator at our hub (128 patients) and at the spoke centers (27 patients) over a 2-year period. Mortality was selected as a primary outcome measure, and post-thrombolysis intracranial hemorrhage (PT-ICH) rate, hospital length of stay (LOS), and discharge modified Rankin Scale (mRS) score were selected as secondary outcome measures. Logistic regression models were used to determine the effect of thrombolysis treatment site on stroke outcomes. Results: Demographic and clinical variables of patients treated at the hub versus spoke sites were similar, except for a lower initial platelet count and a shorter time from ictus onset to needle in the spoke group. With covariates, the treatment site (hub vs spoke) did not have a significant impact on mortality (10.9% vs 11.1%; P = 0.34), nor on PT-ICH (20.3% vs 33.3%; P < 0.35). Site did not reach significance in affecting discharge outcome: 52.3% versus 51.9% of patients had good outcomes (mRS 0–3) and 47.7% versus 48.1% patients had poor outcomes (mRS, 4–6; P = 0.16). Length of stay was also not significantly affected by site: 8.8 days versus 10.7 days (P < 0.23). Conclusion: The hub-and-spoke telemedicine model for acute ischemic stroke treatment seems to carry similar efficacy and safety outcomes at the regional academic hub and spoke centers.