Abstract 159: Current Treatment with Clotting Factors Does not Improve Outcome from Intracranial Hemorrhage After Thrombolysis for Acute Ischemic Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Yazan J Alderazi ◽  
Niravkumar V Barot ◽  
Vivek Misra ◽  
James C Grotta ◽  
Sean I Savitz

Objective & Background: Significant intracranial hemorrhage (sigICH), defined as either symptomatic intracerebral hemorrhage SICH or parenchymal hematoma type 2 (PH2), is a concerning complication of thrombolysis for acute ischemic stroke (AIS). While clotting factors have been incorporated into clinical protocols, the effectiveness of such treatment for sigICH has not been evaluated. We investigated the effects of clotting factors, fresh frozen plasma FFP and cryoprecipitate, in patients with sigICH post thrombolysis. Methods: We retrospectively evaluated all patients with sigICH after TPA for AIS in the prospective University of Texas at Houston Stroke registry; January 2007 - July 2011. We included all patients who received TPA for AIS and subsequently developed sigICH. Patients either received clotting factors (FFP or cryoprecipitate) or conservative management. The primary outcome measure was modified Rankin scale at discharge. The other outcome was death. We collected data on confounding variables: Stroke risk factors, infarct prognostic variables and intracerebral hematoma prognostic variables. Statistical analysis was by Fisher-exact, Chi-square and Mann-Whitney-U tests. Results: Out of 921 patients receiving TPA, sigICH occurred in 50. We excluded 3 because of enrollment in clinical trials. Out of 47 patients, 37 received IV TPA alone and 10 received IV TPA with subsequent intra-arterial therapy. Clotting factors were given in 22/47 (46.8%) patients; 18 received FFP & 9 received cryoprecipitate. The rest received no specific therapies for hemorrhage. There was no difference in stroke severity between groups before and after TPA. The incidence of hydrocephalus was higher in patients receiving clotting factors. There were no differences in outcomes at discharge in either group; the majority of patients in both groups had poor outcomes (mRS was >3). Mortality was high and not different between the two groups. Fibrinogen levels before and after clotting factors did not significantly differ from the patients who received only conservative management. Table 1. Conclusions: We found that clinical outcome of sigICH post TPA is poor. Furthermore, our data suggest that clotting factors do not improve the poor outcome associated with sigICH after t-PA. Our study is limited by small sample size, and the higher incidence of hydrocephalus in those receiving clotting factors may have influenced the outcomes. Nevertheless, our data suggest that new therapies are urgently needed for t-PA associated intracranial hemorrhage.

Author(s):  
Shreyansh Shah ◽  
Li Liang ◽  
Andrzej Kosinski ◽  
Adrian F. Hernandez ◽  
Lee H. Schwamm ◽  
...  

Background Guidelines recommend against the use of intravenous tPA (tissue-type plasminogen activator; IV tPA) in acute ischemic stroke patients with prior ischemic stroke within 3 months. However, there are limited data on the safety of IV tPA in this population. Methods and Results A retrospective observational study of patients ≥66 years of age linked to Medicare claims and treated with IV tPA at Get With The Guidelines–Stroke hospitals (February 2009 to December 2015). We identified 293 patients treated with IV tPA who had a prior ischemic stroke within 3 months and 30 655 with no history of stroke. Patients with prior stroke had a higher stroke severity (median National Institutes of Health Stroke Scale, 11 [6–19] versus 11 [6–18]; absolute standardized difference, 11.2%) and a higher prevalence of cardiovascular comorbidities. Patients with prior stroke had a higher unadjusted risk for symptomatic intracranial hemorrhage (7.7% versus 4.8%) and in-hospital mortality (12.6% versus 8.9%), but these differences were not statistically significant after adjustment. When stratified by prespecified time epochs, the elevated risk for symptomatic intracranial hemorrhage was seen only within the first 14 days (16.3% versus 4.8%; adjusted odds ratio [aOR], 3.7 [95% CI, 1.62–8.43]) but not in other epochs (2.1% versus 4.8%; aOR, 0.38 [95% CI, 0.05–2.79] for 15–30 days and 7.4% versus 4.8%; aOR, 1.36 [95% CI, 0.77–2.40] for 31–90 days). In addition, patients with prior stroke were significantly more likely to have a combined outcome of in-hospital mortality or discharge to hospice (25.9% versus 17.0%; aOR, 1.70 [95% CI, 1.21–2.38]), less likely to be discharged to home (28.3% versus 32.3%; aOR, 0.72 [95% CI, 0.54–0.98]), or to have good functional outcomes at discharge (modified Rankin Scale, 0–1; 11.3% versus 20.0%; aOR, 0.46 [95% CI, 0.24–0.89]). Conclusions Stroke providers need to continue to be vigilant about the safety of IV tPA in patients with prior stroke, particularly those with an event in the previous 14 days.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Daniel Korya ◽  
Mohammad Moussavi ◽  
Siddhart Mehta ◽  
Jaskiran Brar ◽  
Harina Chahal ◽  
...  

Introduction: The list of contraindications for IV tPA in acute ischemic stroke (AIS) is often too long and may lead to physicians opting to offer no treatment for certain strokes. An alternative treatment is proposed in cases where IV tPA is not an option due to time-window restrictions or contraindications. We compared the stroke severity, outcomes and safety of IV eptifibatide when compared with IV tPA. Methods: Patients who presented to a community based university affiliated comprehensive stroke center from 2012-15 with AIS over a two-year period were included in the study. Those who qualified for IV tPA, and were treated, were compared with patients who only received IV eptifibatide. The initial NIH Stroke Score (NIHSS), 24-hour NIHSS, discharge NIHSS (DCNIHSS), discharge mRS (DCmRS) and symptomatic ICH rates were compared with a paired samples t-test to determine significance of difference between the means. SPSS Version 22 was used for all data analysis. Results: A total of 864 patients presented with AIS in the evaluated time period and of those 166 met study criteria. There were 119 patients who received IV tPA alone (group A) and 47 patients received eptifibatide (group B). The mean initial NIHSS, 24-NIHSS, DCNIHSS, DCmRS and percent bleeding complications for group A were: 11.2, 10.8, 8.6, 3.1 and 6%. For group B the figures were: 6.7, 4.8, 4.3, 1.7 and 0%, respectively. Group A was compared with group B in a paired samples T-test and yielded -4.3, -6.2, -6, -1.5 (p=.0001 to .04) for initial, 24-hour, discharge NIHSS and discharge mRS, respectively. The difference between initial and discharge NIHSS between the two groups was -2.7 (p=.009), favoring IV tPA. Conclusion: In patients who are either outside the time-window or with contraindications to IV tPA, eptifibatide may be a safe alternative and appears to be efficacious. None of the patients who were started on eptifibatide had bleeding complications and they had a statistically significant improvement in their level of disability and stroke severity at discharge. A limitation of this study is that patients in group A had significantly worse initial NIHSS compared with group B. To better evaluate the efficacy of eptifibatide, a larger, prospective study should be initiated.


Author(s):  
Elisabeth B Marsh ◽  
Erin Lawrence ◽  
Rafael H Llinas

Background and Objective: The National Institute of Health Stroke Scale (NIHSS) is the most commonly used metric to evaluate stroke severity and improvement following intervention. Despite its advantages as a rapid, reproducible screening tool, it may be too insensitive to adequately capture functional improvement following treatment. We evaluated the difference in rate of improvement by previously accepted criteria (change of ≥4 NIHSS points) versus physician documentation in patients receiving IV tissue plasminogen activator (tPA) for acute ischemic stroke. Methods: Prospectively collected data on all patients receiving IV tPA over a 15 month period were retrospectively reviewed. NIHSS 24 hours post-treatment and on discharge were extrapolated based on examination and compared to NIHSS on presentation. NIHSS scores at post-discharge follow-up were also recorded. Two reviewers evaluated the medical record and determined improvement based on physician documentation. Using tests of proportion, ‘significant improvement’ by NIHSS was compared to physician documentation at each time point. Results: Forty-one patients were treated with IV tPA. The mean admission NIHSS was 8.6 and improved to 6.4 24 hours post-tPA. Twenty-nine of 41 patients (79%) were “better” by documentation; however only 11/41 (27%) met NIHSS criteria for improvement (p compared to documentation <0.001). On discharge, 20/41 patients (49%) met NIHSS criteria for improvement; however a significant difference between physician documentation remained (p=0.04). The mean post-discharge follow-up NIHSS score was 2.0. 20/21 patients (95%) were “better” compared to 16/21 (76%) meeting NIHSS criteria (p=0.08). Conclusion: The NIHSS may inadequately capture functional improvement post-treatment, especially in the days immediately following intervention.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tiffany R Chang ◽  
Karen C Albright ◽  
Rebecca Kruse-Jarres ◽  
Cindy Lessinger ◽  
Amelia K Boehme ◽  
...  

Background: Factor VIII levels may be screened as part of a hypercoagulable work-up in patients with ischemic stroke. However, it is unknown how treatment with IV tPA may affect these levels during the acute phase of ischemic stroke. Methods: From our prospective registry, we identified patients who presented with acute ischemic stroke to our stroke center between July 2008 and April 2011 and determined if factor VIII levels had been measured during the acute hospitalization. We compared mean factor VIII levels using independent sample t test in patients not treated with IV tPA to post-tPA treatment levels using independent samples t tests. Results: Of the 72 patients who had factor VIII levels checked during admission, 25 (34.7%) received IV tPA. The mean factor VIII level was observed to be lower in patients who were treated with tPA (140.8 vs 180.5, p=0.048). Patients who experienced averted stroke (36%, 9/25) had significantly lower mean factor VIII level than patients who completed infarction on diffusion-weighted MRI (64%, 16/25) (132.7 vs 175.2, p=0.002). Of patients with post-tPA factor VIII levels, the mean factor VIII level of those whose samples were drawn within 24 hours of tPA were not different than the mean factor VIII level of those whose samples were drawn more than 24 hours after tPA (p=0.784). Conclusion: Our observations found that factor VIII levels were lower in both patients treated with IV tPA and in patients with averted stroke. As factor VIII levels were drawn after thrombolytic therapy was administered, this raises the question of whether tPA lowers factor VIII levels or if factor VIII can serve as a potential surrogate marker for recanalization. Prospective studies examining factor VIII levels (1) before and after treatment with IV tPA and (2) in comparison to recanalization are needed to clarify this interesting observation.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Amelia K Boehme ◽  
James E Siegler ◽  
Karen C Albright ◽  
Dominique J Monlezun ◽  
Erica M Jones ◽  
...  

Background: Previous research has indicated that women and Blacks have worse outcomes following acute ischemic stroke (AIS). Little research has been done to investigate the influence of race in the presentation and outcome specifically among women with AIS. Methods: AIS patients presenting to two centers in the Stroke Belt (2004-2011) were identified by prospective registries. Men, women who did not identify as Black or White, and in-hospital strokes were excluded. Patient demographics, clinical characteristics, admission National Institutes of Health Stroke Scale (NIHSS) scores, favorable discharge disposition (home or inpatient rehab), time from last seen normal to ED arrival, and functional discharge outcome as measured by the modified Rankin Scale (mRS) were investigated. Patients were divided into 3 groups: (1) not treated with IV t-PA, (2) treated with IV t-PA within 3 hours of symptom onset, and (3) treated with IV t-PA beyond 3 hours. Results: Of the 8763 patients screened, 2217 women met the study criteria (59% White). White women were older (72 vs. 64; p<0.0001), had higher percentage of atrial fibrillation (24% vs. 11%; p<0.0001), lower percentage of diabetes (30% vs. 40%, p<0.0001), lower percentage of hypertension (73% vs. 84%; p<0.0001) and had a higher baseline NIHSS (9 vs. 7; p=0.0045) Administration of tPA was significantly less among Black women (36% Whites vs. 27% Blacks, p<0.0001). White women are at increased odds of receiving tPA treatment (OR=1.43, 95%CI 1.17-1.75, p=0.0005), and remain at increased odds after adjusting for age, baseline NIHSS, time from last seen normal and glucose (OR 1.42, 95% CI 1.11-1.81, p=00044). Despite the significant difference in treatment with IV tPA, White women had increased odds of having a poor functional outcome (OR=1.2, 95% CI 1.02-1.439,p=0.0250) and unfavorable discharge disposition (OR 1.4, 95% CI 1.18-1.67, p=0.0001), but stratifying by tPA treatment groups, race was not found to be predictive of outcome after adjusting for known confounders (i.e., age, glucose, baseline NIHSS, time from last seen normal). Discussion: Unlike data from previous studies, Black women who presented to these two centers with AIS had less severe neurologic deficits on presentation compared to their White counterparts. Despite differences in the proportion of Blacks and Whites treated with IV tPA, race was not significantly associated with outcome. In our study, age and stroke severity_not race_were the primary predictors for poor outcome.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Javaad Ahmad ◽  
Mohammed Hussain ◽  
Siddhart Mehta ◽  
Jaskiran Brar ◽  
Harina Chahal ◽  
...  

Background and Objective: It is considered unconventional to initiate antiplatelet regimen within 24 hours of IV tPa administration in acute ischemic strokes. There has been an increasing amount of literature assessing combination therapy of IV r- tPA and IV Eptifibatide in acute ischemic stroke. Our objectives were to evaluate the safety (hemorrhagic complications) and efficacy (discharge mRS) of administering IV Eptifibatide within the first 24 hours of receiving full dose IV r-tPA respectively. Materials and Methods: All patients that presented to our university affiliated stroke center from 2010-13 with an acute ischemic stroke were included and retrospectively classified into two groups. Group A underwent full dose IV r- tPa (.9 mg/kg) (+/- Endovascular intervention). Group B underwent full dose IV r-tPa (.9mg/kg) and IV Eptifibatide (+/- Endovascular intervention). Epitafibide was administered as a bolus of 135 mcg/kg IV followed by .5 mcg/kg/min for 20 hours. The primary endpoint of bleeding is classified as major (symptomatic intracranial hemorrhage or hemoglobin decrease by >5 mg/dl), minor (asymptomatic intracranial hemorrhage or hemoglobin decrease by 3-5 mg/dl) and insignificant as proposed by TIMI score. The efficacy endpoint was discharge mRS of 0-1 as favorable, with 2 and above being unfavorable. Results: We reviewed 2,016 patients with ischemic stroke, of which 170 received IV tPA. Among the group, 118 received IV r-tPa alone and 52 received combined modalities of IV r-tPa and IV Eptifibatide. In group A, there were 7 patients who had a major complication of symptomatic intracranial hemorrhage, while 1 patient had a minor complication of asymptomatic intracranial hemorrhage. In group B, there were 3 patients who had major complication of symptomatic intracranial hemorrhage and 5 with minor complications of asymptomatic intracranial hemorrhage. In group A , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Of the 52 patients in group B, 18% (n=8) had a favorable outcome. Conclusion: IV Eptifibatide, within the first 24 hours of ischemic stroke in combination with full dose IV r-tPA was found to be safe and efficacious. Further, larger prospective trials are needed to corroborate our findings.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Kristian Barlinn ◽  
Georgios Tsivgoulis ◽  
Andrew D Barreto ◽  
Robert Mikulik ◽  
Maher Saqqur ◽  
...  

Background&Purpose: A recent meta-analysis showed that sonothrombolysis is safe and can double the rate of early recanalization in acute ischemic stroke (AIS). We sought to explore whether patients with severe strokes could clinically benefit from ultrasound amplification of tPA-induced recanalization. Subjects&Methods: We compared functional outcomes at 3 months among randomized AIS patients with pre-treatment NIHSS scores >=10 in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and pilot randomized clinical safety study of sonothrombolysis with microspheres (Definity study). Patients had proximal arterial occlusions identified by baseline TCD and received intravenous (IV) tPA or IV tPA plus continuous 2-hour TCD ultrasound monitoring (=sonothrombolysis). Favorable outcome was defined as modified Rankin Scale (mRS) 0-1 at 3 months. Sustained complete recanalization was defined as Thrombolysis in Brain Ischemia (TIBI) flow grades 4-5 assessed by TCD at 2 hours after tPA bolus. Symptomatic intracranial hemorrhage (sICH) was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS >=4) within 72 hours from stroke onset. Results: A total of 139 AIS patients with severe stroke due to proximal arterial occlusions (mean age 69±13years, 56% men, median NIHSS 17, interquartile range 14-21, range 10-34) were randomized in CLOTBUST (n=105), TUCSON (n=21) and Definity (n=13). A total of 60 (43%) and 79 (57%) patients were randomized to IV tPA and sonothrombolysis, respectively. Patients treated with IV tPA and sonothrombolysis did not differ in terms of age, baseline stroke severity, baseline TIBI grades and onset-to-treatment time. Symptomatic ICH rates were similar in patients treated with IV tPA and sonothrombolysis (5.0% vs. 5.1%; p=0.987). More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA group (38.0% vs. 18.3%; p=0.012). Favorable outcome (mRS 0-1) tended to be more prevalent in the sonothrombolysis than in the IV tPA group (36.6% vs. 23.2%; p=0.104). Conclusions: Our data point to a signal-of-efficacy and provide basis to determine the sample size of a phase 3 randomized trial of sonothrombolysis in patients with severe strokes ( NCT01098981 ).


2014 ◽  
Vol 23 (3) ◽  
pp. e207-e214 ◽  
Author(s):  
Yazan J. Alderazi ◽  
Niravkumar V. Barot ◽  
Hui Peng ◽  
Farhaan S. Vahidy ◽  
Digvijaya D. Navalkele ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Benjamin Maïer ◽  
Jean Philippe Desilles ◽  
Mikael Mazighi

Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.


Stroke ◽  
2021 ◽  
Author(s):  
Alis J. Dicpinigaitis ◽  
Tolga Sursal ◽  
Catherine A. Morse ◽  
Camille Briskin ◽  
Katarina Dakay ◽  
...  

Background and Purpose: Acute ischemic stroke (AIS) is a rare occurrence during pregnancy and the postpartum period. Existing literature evaluating endovascular mechanical thrombectomy (MT) for this patient population is limited. Methods: The National Inpatient Sample was queried from 2012 to 2018 to identify and characterize pregnant and postpartum patients (up to 6 weeks following childbirth) with AIS treated with MT. Complications and outcomes were compared with nonpregnant female patients treated with MT and to other pregnant and postpartum patients managed medically. Complex samples regression models and propensity score matching were implemented to assess adjusted associations and to address confounding by indication, respectively. Results: Among 4590 pregnant and postpartum patients with AIS, 180 (3.9%) were treated with MT, and rates of utilization increased following the MT clinical trial era (2015–2018; 1.9% versus 5.3%, P =0.011). Compared with nonpregnant patients with AIS treated with MT, they experienced lower rates of intracranial hemorrhage (11% versus 24%, P =0.069) and poor functional outcome (50% versus 72%, P =0.003) at discharge. Pregnant/postpartum status was independently associated with a lower likelihood of development of intracranial hemorrhage (adjusted odds ratio, 0.26 [95% CI, 0.09–0.70]; P =0.008) following multivariable analysis adjusting for age, illness severity, and stroke severity. Following propensity score matching, pregnant and postpartum patients treated with MT and those medically managed differed in frequency of venous thromboembolism (17% versus 0%, P =0.001) and complications related to pregnancy (44% versus 64%, P =0.034), but not in functional outcome at discharge or hospital length of stay. Pregnant and postpartum women treated with MT did not experience mortality or miscarriage during hospitalization. Conclusions: This large-scale analysis utilizing national claims data suggests that MT is a safe and efficacious therapy for AIS during pregnancy and the postpartum period. In the absence of prospective clinical trials, population-based cross-sectional analyses such as the present study provide valuable clinical insight.


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