Parenchymal Hemorrhage Type Research Articles

Safety of Standard-dose (.9-mg/kg) Alteplase Intravenous Thrombolysis for Acute Ischemic Stroke in Afro–Caribbeans, French West Indies

Pharmacobiologic data suggested that people of African ancestry were more sensitive to the recombinant tissue plasminogen activator, alteplase, than Caucasians. Furthermore, the higher incidences of hypertension and diabetes mellitus in black populations could contribute to a higher cerebral bleeding risk. However, standard-dose (.9-mg/kg) alteplase safety for stroke has never been evaluated in blacks. This study was undertaken to evaluate standard-dose alteplase safety to treat strokes in an Afro-Caribbean population. Parenchymal hemorrhage and symptomatic intracerebral hemorrhage rates in Afro-Caribbean Martinicans given standard-dose alteplase for acute stroke were evaluated based on prospectively collected data from 2007 to 2010 and compared with those from studies on predominantly Caucasian stroke victims. Parenchymal hemorrhage type 2 and symptomatic intracerebral hemorrhages, as defined by the third European Cooperative Acute Stroke Study, respectively, occurred in 15 (10.1%) and 12 (8.1%) of the 148 thrombolyzed Afro-Caribbeans, respectively. This excess bleeding risk (parenchymal hemorrhage type 2) concerned more patients >70 than those 70years of age or lesser (respectively, 17.6% [13 of 74] vs. 2.7% [2 of 74]). Older age was the only factor significantly associated with a higher parenchymal hemorrhage type 2 risk (P=.02). The excess hemorrhagic risk after standard-dose alteplase infusion into older Afro-Caribbean patients warrants further study to determine the possible role of cerebral microangiopathy and should be evaluated in different black populations.

Abstract T P257: Intramural Competition Significantly Reduces Door-to-Needle Time: Results From Adventist National Stroke Forum Door-to-Needle Time Challenge Process Improvement Project.

Background: Lower Door-to-needle times (DTNT) are associated with better outcomes. The Adventist National Stroke Forum (ANSF) was formed in 2011 to improve stroke care throughout Adventist hospitals. Methods: In 2011, ANSF completed a 4-month regional DTNT reduction competition among 7 Orlando Adventist hospitals. In 2013, ANSF conducted a 6 month national DTNT Competition following : Shawnee Mission Medical Center (KS), Florida Hospital Zephyrhills, Adventist Hinsdale Hospital (IL), Florida Hospital East Orlando, Glendale Adventist Medical Center (CA), Florida Hospital Orlando, and Florida Hospital Altamonte. Stroke teams implemented ways to reduce DTNT. Parenchymal hemorrhage type 2 (PH2) rates and percentage of stroke mimics treated with IV tPA were measured 4-6 months before and 4-6 months during both competitions. Comparison of DTNT between televideo and non-televideo cases is being completed in the national competition. Results: From 6/2011 to 10/2011 the regional study compared data from 27 tPA cases 4 months “before” the study to 28 tPA cases “during” the study. Regional DTNT “before” average (103 min) and median (95 min) times dropped 26% and 18% respectively to “during” average (76 min) and median (76 min). The odds of a DTNT of <60 minutes increased from 7% pre- competition to 33% during the regional competition in Orlando Adventist hospitals (2 of 28 vs. 9 of 27, OR=6.5, 95% CI 1.26 to 33.7). There was no regional increase in either PH2 or treated stroke mimics rates (1 of 28 before vs. 0 of 27 during for both PH2 and stroke mimics treated, OR=2.8947, 95% CI 0.11 to 74.2). Conclusion: A regional DTNT competition among Adventist hospitals produced a significant increase in percentage of patients receiving tPA with DTNT <60 min with no increase in PH-2 or number of stroke mimics treated. Final national competition results will be presented to determine 1) if regional DTNT competition benefits can be generalized nationally, 2) if 2011 Regional DTNT competition gains were sustained among Orlando Adventist hospitals, and 3) if televideo was associated with lower DTNT's.

Selection for Delayed Intravenous Alteplase Treatment Based on a Prognostic Score

Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5-6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran-Mantel-Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5-6 h, testing for net benefit by Cochran-Mantel-Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0-1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale. In the training dataset, limits of 56-95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5-6 h dataset, score limits of 56-95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87-1·47, Cochran-Mantel-Haenszel P = 0·89. More patients achieved modified Rankin score 0-1 (odds ratio 1·44, 1·02-2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01-2·40, P = 0·04; odds ratio 15·6, 3·7-65·8, P = 0·0002, respectively. Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

Retrospective Multicenter Study of Solitaire FR for Revascularization in the Treatment of Acute Ischemic Stroke

The purpose of this study was to evaluate safety and efficacy of the Solitaire FR device in the treatment of patients with acute ischemic stroke secondary to large artery occlusion. We conducted a retrospective study of consecutive patients presenting with acute ischemic stroke treated with Solitaire FR as the first-line device to restore blood flow in 6 experienced European centers. This study was entirely funded and supported by Coviden Neurovascular. An independent Corelab determined modified Thrombolysis in Cerebral Infarction scores on the preprocedure and postprocedure angiograms. Complete revascularization was defined as modified Thrombolysis in Cerebral Infarction 2b or 3 post-Solitaire FR device use. Symptomatic intracranial hemorrhage was defined as parenchymal hemorrhage Type 2 associated with a decline of ≥ 4 points in the National Institutes of Health Stroke Scale score within 24 hours or causing death. Favorable functional outcome was considered as modified Rankin Scale score ≤ 2 at Day 90. We studied 141 patients (mean age, 66 years; median National Institutes of Health Stroke Scale, 18); 74 patients received intravenous tissue-type plasminogen activator before endovascular treatment. Complete revascularization was achieved in 120 of 142 occlusion sites (85%) and good outcome in 77 of 141 (55%) patients. Good outcome was more frequent in patients treated with intravenous tissue-type plasminogen activator than in those without (66% versus 42%; P<0.01). Symptomatic intracranial hemorrhage was reported in 5 patients (4%) and 29 of 141 (20%) patients died or were lost during follow-up (3 cases). This retrospective study with centralized evaluation shows that the use of Solitaire FR is safe and achieves good revascularization rates and functional outcomes in patients with acute ischemic stroke and large artery occlusion.

O-002 A retrospective multicenter study of Solitaire device used for the revascularization in the treatment of acute ischemic stroke

PurposeTo evaluate safety and efficacy of the Solitaire device when used as 1st choice device in the treatment of patients with acute ischemic stroke (AIS) secondary to large artery occlusion.MethodsA...

Abstract 98: Higher Volume Endovascular Stroke Centers Have Decreased Times to Treatment

Background: Currently, no metric exists for door to arterial puncture time for endovascular treatment in acute ischemic stroke. The aim of this study was to determine the timings of each step of endovascular stroke intervention stratified by the volume of procedures at each center. Methods: We retrospectively reviewed patients from seven institutions undergoing endovascular reperfusion therapies for acute ischemic stroke. Patients with anterior circulation strokes treated less than 8 hours from symptoms onset were included. Demographic, radiographic, angiographic and clinical outcomes were collected. The time interval at each milestone from CT acquisition to reperfusion was recorded. Successful reperfusion was defined as achieving a TICI 2B or 3 score as graded by the operator. Symptomatic hemorrhage was defined as a parenchymal hemorrhage type 2 as defined by ECASScriteria. Centers that performed more than 50 intra-arterial stroke interventions annually were considered high volume (HV) centers. A univariate analysis was performed with the Fisher’s exact test for categorical variables and students t-test for continuous variables to compare HV to lower volume (LV) centers. Variables with a p-value &lt; 0.20 were placed in a binary logistic regression model to determine if there were differences in time to treatment between the two groups. Results: A total of 338 patients with a mean age of 67±14 years and mean NIHSS of 18±5 were included. The mean time from CT imaging to groin puncture was 108±73 minutes. The mean time from groin puncture to the placement of a microcatheter in the thrombus was 41±21 minutes and total procedure time 104±55 minutes. There were no differences in demographics, site of vascular occlusion and hemorrhage rates between high volume and lower volume centers. In univariate analysis, HV centers had a lower time from CT imaging to groin puncture (89±57 minutes vs. 154±84 minutes, p&lt;0.001), procedure time (93±46 minutes vs. 129±65 minutes, p&lt;0.001), final infarct volume (79±82 cm 3 vs. 94±106 cm 3 , p&lt;0.03) and higher reperfusion rates (73% vs. 59%, p&lt;0.01). In binary logistic regression modeling HV centers were found to have a shorter CT acquisition to arterial puncture time [OR 0.991, 95%CI (0.986-0.996), p&lt;0.001] and higher reperfusion rates [OR 1.79, 95% CI (1.04-3.12), p&lt;0.03]. Conclusions: Currently there is variability in the time from CT to arterial puncture and total procedure time across institutions, but HV centers appear to have lower times to treatment. Further study is required to determine how to reduce times to treatment and develop a metric for centers to target.

Abstract 2261: Presence of Large Deep White Matter Lesion May Predict Futile Recanalization in Endovascular Therapy for Acute Ischemic Stroke

Background: A subset of stroke patients treated with endovascular recanalization therapy suffers poor outcome despite good arterial recanalization. The aim of this study is to identify whether large ischemic lesion in deep white matter (DWM) on diffusion weighted imaging (DWI) prior to therapy predicts futile recanalization. Method: Consecutive acute stroke patients with anterior circulation ischemia whose artery had been recanalized at Thrombolysis in Myocardial Infarct (TIMI) flow grade 2 or 3 following endovascular therapy were included. All patients underwent CT and MRI before endovascular therapy. We defined large DWI - DWM lesion if DWI showed the hyperintense lesion in the DWM which mostly extended between anterior and posterior horn of the lateral ventricle. We identified Alberta Stroke Program Early CT Scores (ASPECTS) of CT and DWI, and volumes measured on initial DWI and mean transit time of perfusion weighted images. We assessed the prevalence of TIMI grade 3 recanalization and parenchymal hemorrhage type 2, and final ischemic lesion volume after endovascular therapy. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Futile recanalization was defined as a 30-day modified Rankin Scale score 3 to 6 despite recanalization at TIMI grade 2 or 3. Univariate and multivariate regression analyses were performed to identify predictors of futile recanalization. Results: Partial or complete recanalization (TIMI grade 2 or 3) was observed in 35 of 46 patients (76 %). Of the 35 patients, futile recanalization was observed in 20 patients (57 %). Patients with futile recanalization had older age (median, 74 versus 58 years old, p = 0.053), higher initial NIHSS score (median, 17 versus 9, p = 0.042), pre-treatment large DWI - DWM lesion (45 versus 9 %, p = 0.022), and larger final ischemic lesion volume (median, 37 versus 9 ml, p = 0.003). ASPECTS of CT (median, 9 versus 9, p = 0.527) and DWI (median, 8 versus 8, p = 0.943) and initial ischemic lesion volumes on DWI (median, 21 versus 14 ml, p = 0.230) and on mean transit time (median, 189 versus 192 ml, p = 0.976) did not demonstrate statistically significance between patients with and without futile recanalization. There were also no significant differences between the outcome groups in times from stroke onset to imaging or endovascular therapy. Logistic regression analysis demonstrated that large DWI - DWM lesion was an independent predictor of futile recanalization (OR 10.40, 95 % CI 1.03 to 105.21, p = 0.047). Conclusion: Patients who have large pre-treatment DWI - DWM lesion may be poor candidates for endovascular therapy.

Prevalence of MRI-defined recent silent ischemia and associated bleeding risk with thrombolysis

Uncertainties about the frequency and the associated bleeding risk of recent silent ischemia (RSI), incidentally found on pretreatment MRI, in candidates for thrombolysis require clarification because exclusion from therapy is a serious consequence for patients with such MRI findings.We retrospectively analyzed the fluid-attenuated inversion recovery (FLAIR)/diffusion-weighted imaging (DWI) obtained before IV thrombolysis in 115 patients to search for MRI-defined RSI; these corresponded to well-developed FLAIR/DWI brain hyperintensities (RSI+), as distinct from the acute index ischemia, which typically lacked FLAIR changes. Patients without such findings were assigned to the RSI- group. Groups were compared for baseline characteristics and for rates of symptomatic and asymptomatic hemorrhagic transformation (HT) using odds ratios (OR) and their 95%confidence intervals (CI).We observed RSI in 21 patients (18.3%). The mean (SD) volume of RSI was 6.5 (12) mL (interquartile range 0.6-9). None of the baseline parameters differed between groups. There was no significant difference in rates of any type of HT between groups. Parenchymal hemorrhage type 1 or type 2 according to European Cooperative Acute Stroke Study criteria occurred in 2 (10%) RSI+ patients and in 10 (11%) RSI- patients (OR 0.88; 95% CI 0.18-4.37). Symptomatic HT, defined according to National Institute of Neurological Disorders and Stroke criteria, occurred in 1 (5%) RSI+ patient and in 10 (11%) RSI- patients (OR 0.42; 95% CI 0.05-3.47).We found that 18.3% of patients with acute stroke treated by IV thrombolysis in a stroke unit had RSI on pretreatment MRI. However, the presence of RSI was not associated with an increased risk of asymptomatic or symptomatic HT.

Prevalence of MRI-defined recent silent ischemia and associated bleeding risk with thrombolysis

Uncertainties about the frequency and the associated bleeding risk of recent silent ischemia (RSI), incidentally found on pretreatment MRI, in candidates for thrombolysis require clarification because exclusion from therapy is a serious consequence for patients with such MRI findings. We retrospectively analyzed the fluid-attenuated inversion recovery (FLAIR)/diffusion-weighted imaging (DWI) obtained before IV thrombolysis in 115 patients to search for MRI-defined RSI; these corresponded to well-developed FLAIR/DWI brain hyperintensities (RSI+), as distinct from the acute index ischemia, which typically lacked FLAIR changes. Patients without such findings were assigned to the RSI- group. Groups were compared for baseline characteristics and for rates of symptomatic and asymptomatic hemorrhagic transformation (HT) using odds ratios (OR) and their 95%confidence intervals (CI). We observed RSI in 21 patients (18.3%). The mean (SD) volume of RSI was 6.5 (12) mL (interquartile range 0.6-9). None of the baseline parameters differed between groups. There was no significant difference in rates of any type of HT between groups. Parenchymal hemorrhage type 1 or type 2 according to European Cooperative Acute Stroke Study criteria occurred in 2 (10%) RSI+ patients and in 10 (11%) RSI- patients (OR 0.88; 95% CI 0.18-4.37). Symptomatic HT, defined according to National Institute of Neurological Disorders and Stroke criteria, occurred in 1 (5%) RSI+ patient and in 10 (11%) RSI- patients (OR 0.42; 95% CI 0.05-3.47). We found that 18.3% of patients with acute stroke treated by IV thrombolysis in a stroke unit had RSI on pretreatment MRI. However, the presence of RSI was not associated with an increased risk of asymptomatic or symptomatic HT.

A Mouse Model of Hemorrhagic Transformation by Delayed Tissue Plasminogen Activator Administration After In Situ Thromboembolic Stroke

thrombolytic treatment with tissue plasminogen activator (tPA) improves outcome of patients with stroke who can be treated within 3 hours of symptom onset. However, delayed treatment with tPA leads to increased risk of hemorrhagic transformation and can result in enhanced brain injury. The purpose of this study is to validate a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA. mice were anesthetized and thrombin was injected into the middle cerebral artery to induce the formation of a clot as described by Orset et al. To induce reperfusion, tPA (10 mg/kg) was intravenously administered 20 minutes or 3 hours after thrombin injection. thrombin produced a clot in 83.1% of the animals, which caused focal ischemia determined 24 hours after the injection. Different degrees of bleeding were found in the middle cerebral artery occlusion group, including hemorrhagic infarction type 1 (HI-1) in 46.2%, hemorrhagic infarction type 2 (HI-2) in 30.8% and parenchymal hemorrhage type 1 in 23.0%. Administration of tPA 20 minutes after the occlusion produced an effective reperfusion in 62.5% of the animals and reduced both infarct volume and appearance of severe hemorrhage (10% nonhemorrhage, 80% HI-1 and 10% HI-2). However, administration of tPA 3 hours after the occlusion led to effective reperfusion in 47.1% of the animals, did not reduce infarct volume, caused hemorrhagic transformation (25% HI-1, 37.5% HI-2, and 37.5% parenchymal hemorrhage type 1), and increased hemorrhage and brain swelling. we have set up a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA similar to that observed in humans.

Initial experience with the Penumbra Stroke System for recanalization of large vessel occlusions in acute ischemic stroke

The Penumbra system is a newly approved mechanical device for the treatment of acute stroke designed for better and faster recanalization. We describe our initial experience with the use of this device. We studied 27 consecutive patients with acute ischemic strokes due to arterial occlusions presenting at our center from January to October 2009. The primary outcome was the degree of recanalization measured by thrombolysis in myocardial infarction (TIMI grade 2/3) at the end of the procedure. Secondary end points were the proportion of patients who achieved a modified Rankin scale (mRS) ≤2 at 3months, all-cause mortality and intracerebral hemorrhage (ICH) on non contrast computed tomography at 24h. Procedural complications were also recorded. Of 27 patients (13 male, mean age 61years) in the study, 22 (81%) patients had anterior circulation strokes and five (18%) had posterior circulation strokes. Twenty-three (85%) patients achieved TIMI grade 2/3 recanalization at completion of the procedure. Excluding five patients who needed use of a second device, the Penumbra system achieved TIMI grade 2/3 recanalization in 67% of patients. Thirteen (48%) patients had mRS ≤2 at 3-month follow-up. Procedural and post-procedural complications included vasospasm (3.7%), distal emboli (48.1%), and ICH (33.3%). The distribution of ICH is as follows: hemorrhagic infarct type 1 (25.9%), parenchymal hemorrhage type 1 (3.7%), and parenchymal hemorrhage type 2 (3.7%). All-cause mortality was 19%. High recanalization rates and good clinical outcomes are achievable with the Penumbra system. Complication rates are comparable to a previously published literature.

The Argatroban and tPA Stroke Study

ABSTRACTBackground: The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute ischemic stroke is related to clot lysis and arterial recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. However, human data on this combination are limited. Design: We report an update of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose escalation, safety, and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 h. After standard dose intravenous rtPA administration, a 100-μg/kg bolus of argatroban followed by infusion of 1 μg/kg per min for 48 h was adjusted to a target partial thromboplastin time of 1.75 times baseline. Results: Twenty patients with middle cerebral artery occlusions (including 13 men) have been enrolled, with a mean ± SD age of 61 ± 13 years. Baseline median National Institute of Health Stroke Scale score was 12.5 (range, 3–25). The mean ± SD time from symptom onset to argatroban bolus administration was 177 ± 56 min. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 2 patients and there was 1 death. Recanalization was complete in 7 patients and partial in another 7, and reocclusion occurred in 4 within 2 h of rtPA bolus administration. Conclusion: The combination of low-dose argatroban and intravenous rtPA may be safe, and produce faster and more complete recanalization, but a larger cohort of patients is required to confirm this pilot study.

Thrombolysis with alteplase for acute ischemic stroke: review of SITS-MOST and other Phase IV studies

Thrombolytic therapy is the only approved therapy for acute ischemic stroke patients. As part of the European approval process, the Safe Implementation of Thrombolysis in Stroke – Monitoring Study (SITS-MOST) was demanded as a Phase IV study to evaluate the safety and efficacy of alteplase in a 3-h time-window. This article summarizes SITS-MOST and compares it with other Phase IV studies. Between 2002 and 2006, 6483 patients were included in 285 centers; median age was 68 years, median National Institutes of Health Stroke Scale (NIHSS) score was 12 and the median time-window was 140 min. The rate of symptomatic intracerebral hemorrhages, defined as parenchymal hemorrhage type 2 combined with a neurological deterioration of at least 4 points on NIHSS, was 1.7% within 24 h after treatment. Symptomatic hemorrhages as defined by the National Institute of Neurological and Communicative Disorders and Stroke criteria occurred in 7.3% of patients. The 3-month mortality was 11.3% and the rate of good clinical outcome (modified Rankin Score 0–2) was 55%. There were no major differences between experienced and inexperienced centers regarding safety or efficacy. The results of SITS-MOST are comparable with the results of the randomized placebo-controlled trials and other Phase IV studies such as standard treatment with Alteplase to Reverse Stroke and Canadian Alteplase for Stroke Effectiveness Study. They confirm that intravenous alteplase is safe and effective in routine clinical practice when used for acute stroke within 3 h of stroke onset, even in centers with little previous experience of thrombolytic therapy but only if the licensing approval criteria are strictly followed. These findings should encourage wider use of thrombolytic therapies for suitable stroke patients treated in stroke centers.

Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic stroke

Hemorrhagic transformation (HT) after cerebral ischemia seems to be related to the endothelial disruption secondary to the ischemic process. Albuminuria has recently been found to be a marker of chronic endothelial damage. To investigate the relationship between albuminuria and HT in patients with acute ischemic stroke. We studied 200 patients (51.5% men, age 72.5 +/- 8.5 years) with ischemic stroke within the first 24 hours of evolution. HT development was assessed on CT performed between days 4 and 7 of evolution and classified according to the ECASS II criteria. Urinary samples were collected within the first 3 hours after admission and the presence of albuminuria, which was considered to be present when the ratio albumin-to-creatinine was > or =30 mg/g creatinine, was determined by nephelometry within the first 24 hours of evolution. Forty-nine patients (24.5%) had albuminuria and 36 (18%) had HT on the second CT scan. After adjusting for potential confounders including a previous history of diabetes mellitus, hypertension and atrial fibrillation, stroke severity, the presence of early signs of ischemia and leukoaraiosis on the baseline CT scan, and IV anticoagulant treatment, logistic regression analysis showed that albuminuria was independently associated with HT (OR, 7.45; 95% CI 2.30 to 24.16). Moreover, albuminuria was also a significant and independent predictor of parenchymal hemorrhage type 1 and 2 (OR, 8.30; 95% CI 1.77 to 38.89). Albuminuria is an independent predictor of hemorrhagic transformation, and particularly of the most severe bleedings, in patients with acute ischemic stroke. Due to the small number of events, the predictive capacity of albuminuria should be confirmed in larger studies.

Argatroban tPA Stroke Study

The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute stroke is linked to clot lysis and artery recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. There are no human data on this combination. We report the first phase of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose-escalation, safety and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours. After standard-dose intravenous rtPA administration, a 100-mug/kg bolus of argatroban followed by infusion of 1 mug/kg per minute for 48 hours was adjusted to a target partial thromboplastin time of 1.75 times that of the control group. Fifteen patients (including 10 men) were enrolled, with a mean +/- SD age of 61 +/- 13 years. All patients had middle cerebral artery occlusions. Baseline median National Institute of Health Stroke Scale score was 14 (range, 4-25). The mean +/- SD time from symptom onset to argatroban bolus administration was 172 +/- 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 1 patient and there was 1 death. Recanalization was complete in 6 patients and partial in another 4, and reocclusion occurred in 3 within 2 hours of rtPA bolus administration. The safety of low-dose argatroban combined with intravenous rtPA may be within acceptable limits, and its efficacy for producing fast and complete recanalization is promising, but a larger cohort of patients is required to confirm these preliminary observations.