The safety and efficacy of tPA intravenous thrombolysis for treating acute ischemic stroke patients with a history of cerebral hemorrhage

Background and purpose On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. Methods The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. Results This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. Conclusions These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

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Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach

Therapeutic Advances in Neurological Disorders ◽

10.1177/17562864211021182 ◽

2021 ◽

Vol 14 ◽

pp. 175628642110211

Author(s):

Georgios Magoufis ◽

Apostolos Safouris ◽

Guy Raphaeli ◽

Odysseas Kargiotis ◽

Klearchos Psychogios ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Symptom Onset ◽

Time Windows ◽

Intravenous Thrombolysis ◽

Inclusion Criteria ◽

Stroke Patients ◽

Treatment Algorithms ◽

Late Presenters

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

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Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽

10.3390/biom11030347 ◽

2021 ◽

Vol 11 (3) ◽

pp. 347

Author(s):

Zsuzsa Bagoly ◽

Barbara Baráth ◽

Rita Orbán-Kálmándi ◽

István Szegedi ◽

Réka Bogáti ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intravenous Thrombolysis ◽

Fibrin Clot ◽

Clot Lysis ◽

Stroke Patients ◽

Plasmin Inhibitor ◽

Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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Elevated Levels of Inflammation Markers Predict Poor Outcomes in Acute Ischemic Stroke Patients After Intravenous Thrombolysis

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2020.105587 ◽

2021 ◽

Vol 30 (3) ◽

pp. 105587

Author(s):

Dan Hu ◽

Caixia Ding ◽

Xuemei Jiang ◽

Jing Xiao ◽

Chuanyou Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intravenous Thrombolysis ◽

Inflammation Markers ◽

Stroke Patients ◽

Poor Outcomes

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Recanalization between 1 and 24 hours after t-PA therapy is a strong predictor of cerebral hemorrhage in acute ischemic stroke patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2008.01.013 ◽

2008 ◽

Vol 270 (1-2) ◽

pp. 48-52 ◽

Cited By ~ 16

Author(s):

Kazumi Kimura ◽

Yasuyuki Iguchi ◽

Kensaku Shibazaki ◽

Kazuto Kobayashi ◽

Junichi Uemura ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Cerebral Hemorrhage ◽

Strong Predictor ◽

Stroke Patients

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Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Unsuspected Infective Endocarditis

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2020.105502 ◽

2021 ◽

Vol 30 (3) ◽

pp. 105502

Author(s):

Mangala Gopal ◽

Sushil Lakhani ◽

Vivien H. Lee

Keyword(s):

Ischemic Stroke ◽

Infective Endocarditis ◽

Acute Ischemic Stroke ◽

Intravenous Thrombolysis ◽

Stroke Patients

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Abstract 1122‐000214: Clinical Factors Associated rTPA Administration in Acute Ischemic Stroke Patients with History of Atrial Fibrillation

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000214 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Chase A Rathfoot ◽

Camron Edressi ◽

Carolyn B Sanders ◽

Krista Knisely ◽

Nicolas Poupore ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Medical History ◽

Clinical Decision Making ◽

Past Medical History ◽

Clinical Factors ◽

Stroke Patients ◽

Factors Associated ◽

History Of

Introduction : Previous research into the administration of rTPA therapy in acute ischemic stroke patients has largely focused on the general population, however the comorbid clinical factors held by stroke patients are important factors in clinical decision making. One such comorbid condition is Atrial Fibrillation. The purpose of this study is to determine the clinical factors associated with the administration of rtPA in Acute Ischemic Stroke (AIS) patients specifically with a past medical history of Atrial Fibrillation (AFib). Methods : The data for this analysis was collected at a regional stroke center from January 2010 to June 2016 in Greenville, SC. It was then analyzed retrospectively using a multivariate logistic regression to identify factors significantly associated with the inclusion or exclusion receiving rtPA therapy in the AIS/AFib patient population. This inclusion or exclusion is presented as an Odds Ratio and all data was analyzed using IBM SPSS. Results : A total of 158 patients with Atrial Fibrillation who had Acute Ischemic Strokes were identified. For the 158 patients, the clinical factors associated with receiving rtPA therapy were a Previous TIA event (OR = 12.155, 95% CI, 1.125‐131.294, P < 0.040), the administration of Antihypertensive medication before admission (OR = 7.157, 95% CI, 1.071‐47.837, P < 0.042), the administration of Diabetic medication before admission (OR = 13.058, 95% CI, 2.004‐85.105, P < 0.007), and serum LDL level (OR = 1.023, 95% CI, 1.004‐1.042, P < 0.16). Factors associated with not receiving rtPA therapy included a past medical history of Depression (OR = 0.012, 95% CI, 0.000‐0.401, P < 0.013) or Obesity (OR = 0.131, 95% CI, 0.034‐0.507, P < 0.003), Direct Admission to the Neurology Floor (OR = 0.179, 95% CI, 0.050‐0.639, P < 0.008), serum Lipid level (OR = 0.544, 95% CI, 0.381‐0.984, P < 0.044), and Diastolic Blood Pressure (OR = 0.896, 95% CI, 0.848‐0.946, P < 0.001). Conclusions : The results of this study demonstrate that there are significant associations between several clinical risk factors, patient lab values, and hospital admission factors in the administration of rTPA therapy to AIS patients with a past medical history of Atrial Fibrillation. Further research is recommended to determine the extent and reasoning behind of these associations as well as their impact on the clinical course for AIS/AFib patients.

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Abstract MP86: Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Acute Ischemic Stroke Patients by History of Hypertension and Use of Antihypertensive Medications

Circulation ◽

10.1161/circ.131.suppl_1.mp86 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Tan Xu ◽

Yonghong Zhang ◽

Yingxian Sun ◽

Chung-Shiuan Chen ◽

Jing Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Treatment Group ◽

Acute Ischemic Stroke ◽

Hospital Discharge ◽

Odds Ratio ◽

Recurrent Stroke ◽

Stroke Patients ◽

Antihypertensive Medications ◽

History Of

Introduction: The effects of blood pressure (BP) reduction on clinical outcomes among acute stroke patient remain uncertain. Hypothesis: We tested the effects of immediate BP reduction on death and major disability at 14 days or hospital discharge and 3-month follow-up in acute ischemic stroke patients with and without a previous history of hypertension or use of antihypertensive medications. Methods: The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) randomly assigned patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP) to receive antihypertensive treatment (N=2,038) or to discontinue all antihypertensive medications (N=2,033) during hospitalization. Randomization was stratified by participating hospitals and use of antihypertensive medications. Study outcomes were assessed at 14 days or hospital discharge and 3-month post-treatment follow-up. The primary outcome was death and major disability (modified Rankin Scale score≥3), and secondary outcomes included recurrent stroke and vascular events. Results: Mean SBP was reduced 12.7% in the treatment group and 7.2% in the control group within 24 hours after randomization (P<0.001). Mean SBP was 137.3 mmHg in the treatment group and 146.5 in the control group at day 7 after randomization (P<0.001). At 14 days or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups by subgroups. At the 3-month follow-up, recurrent stroke was significantly reduced in the antihypertensive treatment group among patients with a history of hypertension (odds ratio 0.43, 95% CI 0.24-0.75, P=0.003) and among patients with a history of use of antihypertensive medications (odds ratio 0.41, 95% CI 0.20-0.84, P=0.01). All-cause mortality (odds ratio 2.84, 95% CI 1.11-7.27, P=0.03) was increased among patients without a history of hypertension. Conclusion: Immediate BP reduction lowers recurrent stroke among acute ischemic stroke patients with a previous history of hypertension or use of antihypertensive medications at 3 months. On the other hand, BP reduction increases all-cause mortality among patients without a history of hypertension.

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