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Background: A randomized trial of concurrent recombinant tissue-type plasminogen activator (r-tPA) + thrombin-inhibition with Argatroban in stroke patients recently demonstrated safety and signal of efficacy compared to r-tPA alone, but patients having endovascular therapy (EVT) were excluded. The current study intended to study feasibility and safety of concurrent r-tPA and Argatroban in patients undergoing EVT., Methods: We conducted a single-arm, feasibility, and safety study of patients that received standard-dose r-tPA, had intracranial large vessel occlusions, and underwent EVT within 6 hours of stroke onset. During r-tPA, a 100 μg/kg Argatroban bolus, followed by 12-hour infusion, targeted an activated Partial Thromboplastin Time (aPTT) 2.25 timesbaseline. Feasibility was defined as ability to combine treatments without EVT time-metric delays, compared to cotemporaneous r-tPA + EVT treatments. Safety was incidence of symptomatic intracerebral hemorrhage (sICH), systemic hemorrhage, or EVT complications., Results: All preplanned 10 patients were enrolled. Arterial occlusions were middle cerebral artery (n = 8), internal carotid artery (n = 1), and posterior cerebral artery (n = 1). All received Argatroban before EVT and completed infusions. There were no delays in time-metrics compared to nonstudy patients during the same period. Nine patients achieved excellent angiographic reperfusion (Thrombolysis In Cerebral Ischemia [TICI] ≥2b); with 7 complete (TICI = 3). There were no sICH, systemic hemorrhage, or EVT complications. At 90 days, 6 (60%) patients had a modified Rankin Scale of 0-2 and none died., Conclusions: In patients treated with r-tPA and EVT, concomitant Argatroban is feasible, does not delay EVT provision, produces high rates of recanalization, is probably safe, and warrants further study., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To use data from a large multicenter trial to assess the role and significance of chest radiograph (CXR) in the initial evaluation of acute stroke., Methods: Predefined clinical characteristics of patients who had recorded data on CXR examination during the initial evaluation were collected. We compared features of patients who had a CXR done before IV thrombolytics with those who did not. Rates of adverse cardiopulmonary events, intubation, and in-hospital mortality were also compared. Logistic regression analysis was performed to evaluate for the association of CXR performance with door-to-needle time ≥60 minutes., Results: In a cohort of 615 patients, 243 had CXR done before IV thrombolytics. Patients with CXR before treatment had significantly higher admission neurologic deficit, initial respiratory rates, and door-to-needle time than those with CXR after treatment. The rates of cardiopulmonary adverse events in the first 24 hours of admission, endotracheal intubation in the first 7 hours, and in-hospital mortality were not different between the 2 groups. Patients with CXR done before treatment had longer mean door-to-needle times than those without pretreatment radiography (75.8 vs 58.3 minutes, p = 0.0001). Performance of CXR was independently associated with door-to-needle time ≥60 minutes (odds ratio 2.78, 95% confidence interval 1.97-3.92; p = 0.00001)., Conclusions: Performance of CXR prior to IV thrombolytics prolongs door-to-needle time in acute ischemic stroke patients. CXR before treatment should be reserved for situations wherein acute cardiopulmonary conditions would otherwise preclude the administration of IV thrombolytics or substantially influence management., (© 2016 American Academy of Neurology.)

Background: Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option., Objective: To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH., Methods: We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion., Results: Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups., Conclusions: We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition., (Published by Elsevier Inc.)

Dabigatran etexelate is a new oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration to prevent stroke in patients with nonvalvular atrial fibrillation. A 51-year-old man with a history of atrial fibrillation who was taking dabigatran presented with an acute ischemic stroke. The patient had a normal international normalized ratio, activated partial thromboplastin time, and an elevated thrombin time of 26.4 seconds. Recanalization of the middle cerebral artery with intravenous tissue plasminogen activator was apparent on digital subtraction angiography, and there was no evidence of intracerebral hemorrhage on the repeat computed tomographic scan. This is the first report of a patient who was taking dabigatran etexilate and who had an ischemic stroke caused by a middle cerebral artery occlusion, with an elevated thrombin time and radiographic recanalization with intravenous tissue plasminogen activator without evidence of hemorrhagic transformation., (Published by Elsevier Inc.)

Objective: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS).Methods: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score.Results: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up).Interpretation: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218. [ABSTRACT FROM AUTHOR]