scholarly journals SWATH-MS for prospective identification of protein blood biomarkers of rtPA-associated intracranial hemorrhage in acute ischemic stroke: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bartosz Karaszewski ◽  
Anna Gójska-Grymajło ◽  
Paulina Czaplewska ◽  
Bartosz Jabłoński ◽  
Aleksandra E. Lewandowska ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Blood Biomarkers ◽  
Stroke Research ◽  
Clinical Biomarkers ◽  
Prospective Assessment ◽  
Pre Treatment ◽  
Complex Project

AbstractIntravenous recombinant tissue plasminogen activator (rtPA) is, besides mechanical thrombectomy, the highest class evidence based reperfusion treatment of acute ischemic stroke (AIS). The biggest concern of the therapy is symptomatic intracranial hemorrhage (sICH), which occurs in 3–7% of all treated patients, and is associated with worse functional outcome. Finding a method of the powerful identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research. To address this problem, we designed a complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of rtPA-associated ICH. In this paper we present results of blood proteomic and peptide analysis of pilot 41 AIS patients before rtPA administration (the test ICH group, n = 9 or the controls, without ICH, n = 32). We demonstrated that pre-treatment blood profiles of 15 proteins differ depending on whether the patients develop rtPA-associated ICH or not. SWATH-MS quantification of serum or plasma proteins might allow for robust selection of blood biomarkers to increase the prospective assessment of rtPA-associated ICH over that based solely on clinical and neuroimaging characteristics.

Safety and efficacy of mechanical thrombectomy in acute ischemic stroke of anticoagulated patients

2018 ◽  
Vol 10 (12) ◽  
pp. e29-e29 ◽  
Author(s):  
Vincent L’Allinec ◽  
Marielle Ernst ◽  
Mathieu Sevin-Allouet ◽  
Nathalie Testard ◽  
Béatrice Delasalle-Guyomarch ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Mechanical Thrombectomy ◽  
Univariate Analysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Reperfusion Therapy ◽  
Safety And Efficacy ◽  
Risk Of Death ◽  
Anticoagulated Patients

BackgroundAnticoagulated patients (APs) are currently excluded from acute ischemic stroke reperfusion therapy with intravenous recombinant tissue plasminogen activator (IV-rtPA); however, these patients could benefit from mechanical thrombectomy (MT). Evidence for MT in this condition remains scarce. The aim of this study was to analyze the safety and efficacy of MT in APs.MethodsWe analyzed three patient groups from two prospective registries: APs with MT (AP-MT group), non-anticoagulated patients treated with MT (NAP-MT group), and non-anticoagulated patients treated with IV-rtPA and MT (NAP-IVTMT group). Univariate and multivariate logistic regression were used to evaluate treatment efficacy with modified Rankin Scale (mRS) ≤2 and safety (radiologic intracranial hemorrhage (rICH), symptomatic intracranial hemorrhage (sICH) and death rate at 3 months) between groups.Results333 patients were included in the study, with 44 (12%) in the AP-MT group, 105 (31%) in the NAP-MT group, and 188 (57%) in the NAP-IVTMT group. Univariate analysis showed that the AP-MT group was older (P<0.001), more often had atrial fibrillation (P<0001), and had a higher ASPECTS (P<0.006 and P<0.002) compared with the NAP-MT group and NAP-IVTMT groups, respectively. Multivariate analysis showed that the AP-MT group had a lower risk of rICH (OR 2.77, 95% CI 1.01 to 7.61, P=0.05) but a higher risk of death at 3 months (OR 0.26, 95% CI 0.09 to 0.76, P=0.01) compared with the NAP-IVTMT group. No difference was found between the AP-MT and NAP-MT groups.ConclusionsWith regard to intracranial bleeding and functional outcome at 3 months, MT in APs seems as safe and efficient as in NAPs. However, there is a higher risk of death at 3 months in the AP-MT group compared with the NAP-IVTMT group.

scholarly journals Not only the Sugar, Early infarct sign, hyperDense middle cerebral artery, Age, Neurologic deficit score but also atrial fibrillation is predictive for symptomatic intracranial hemorrhage after intravenous recombinant tissue plasminogen activator

2017 ◽  
Vol 08 (01) ◽  
pp. 049-054 ◽  
Author(s):  
Sombat Muengtaweepongsa ◽  
Pornpoj Prapa-Anantachai ◽  
Pornpat A. Dharmasaroja
Keyword(s):  
Heart Disease ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Cerebral Artery ◽  
Recombinant Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
History Of ◽  
Symptomatic Intracranial Hemorrhage ◽  
Hyperdense Middle Cerebral Artery

ABSTRACTBackground: Symptomatic intracranial hemorrhage (sICH) is the most unwanted adverse event in patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (i.v. rt-PA). Many tool scores are available to predict the probability of sICH. Among those scores, the Sugar, Early infarct sign, hyperDense middle cerebral artery, Age, Neurologic deficit (SEDAN) gives the highest area under the curve-receiver operating characteristic value. Objective: We aimed to examine any factors other than the SEDAN score to predict the probability of sICH. Methods: Patients with acute ischemic stroke treated with i.v. rt-PA within 4.5 h time window from January 2010 to July 2012 were evaluated. Compiling demographic data, risk factors, and comorbidity (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation (AF), ischemic heart disease, valvular heart disease, previous stroke, gout, smoking cigarette, drinking alcoholic beverage, family history of stroke, and family history of ischemic heart disease), computed tomography scan of patients prior to treatment with rt-PA, and assessing the National Institutes of Health Stroke Scale (NIHSS) score for the purpose of calculating SEDAN score were analyzed. Results: Of 314 patients treated with i.v. rt-PA, there were 46 ICH cases (14.6%) with 14 sICH (4.4%) and 32 asymptomatic intracranial hemorrhage cases (10.2%). The rate of sICH occurrence was increased in accordance with the increase in the SEDAN score and AF. Age over 75 years, early infarction, hyperdense cerebral artery, baseline blood sugar more than 12 mmol/l, NIHSS as 10 or more, and AF were the risk factors to develop sICH after treated with rt-PA at 1.535, 2.501, 1.093, 1.276, 1.253, and 2.492 times, respectively. Conclusions: Rather than the SEDAN score, AF should be a predictor of sICH in patients with acute ischemic stroke after i.v. rt-PA treatment in Thai population.

Abstract 60: Synthesis Expansion: Randomized Trial On Primary Endovascular Treatment Vs. Standard Intravenous Recombinant Tissue Plasminogen Activator For Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Alfonso Ciccone ◽  
Luca Valvassori ◽  
Edoardo Boccardi ◽  
Roberto Sterzi ◽  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Intracranial Hemorrhage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Neurological Deterioration ◽  
Tissue Plasminogen ◽  
H 30

Background: As compared with systemic i.v. thrombolytic therapy, primary endovascular treatment results in a higher rate of patency of the ischemic stroke-related cerebral artery. However, the comparative clinical efficacy of the two approaches has not been carefully studied. Methods: We randomly assigned a total of 362 patients with acute ischemic stroke seen within 4.5 h from symptoms onset to endovascular treatment (i.e., intra-arterial thrombolysis with recombinant tissue plasminogen activator - t-PA - if necessary, associated to or substituted by mechanical clot disruption and/or retrieval) or i.v. t-PA administered according to EU labeling. The purpose of the study was to determine the proportion of independent survivors at three months. Safety endpoints included symptomatic intracranial hemorrhage, death and other serious adverse events. Results: A total of 181 patients were assigned to undergo endovascular treatment, and 181 to receive i.v. t-PA. Median time from stroke onset to start to treatment was 3 h 45 min for endovascular treatment (range: 1 h 30 min to 5 h 55 min) and 2 h 45 min (range: 55 min to 4 h 30 min) for i.v. t-PA (p=0.002). All the randomized patients were assessed at 3 months and analyzed. We will present analyses comparing the effect of endovascular treatment with i.v. t-PA on a) the primary outcome (proportion of patients alive and independent at 3 months as assessed by the modified Rankin scale) adjusted for key covariates, b) death from any cause within 3 months, c) events within 7 days: fatal and non fatal symptomatic intracranial hemorrhages, fatal and non fatal neurological deterioration attributed to brain swelling from the initial ischemic stroke, fatal and non fatal neurological deterioration not attributed to swelling or intracranial hemorrhage, fatal and non fatal recurrent ischemic stroke, death from any cause. Conclusions: Data from the trial will provide new evidence on the balance of risk and benefit of endovascular treatment, as compared to systemic thrombolysis, among patients with acute ischemic stroke.

Association of admission leukocyte count with clinical outcomes in acute ischemic stroke patients undergoing intravenous thrombolysis with recombinant tissue plasminogen activator

2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Leukocyte Count ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Functional Independence ◽  
Tissue Plasminogen ◽  
Poor Outcomes

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

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

Biomolecules ◽  
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.

Bivalirudin for Endovascular Intervention in Acute Ischemic Stroke: Case Report

Neurosurgery ◽  
2004 ◽  
Vol 54 (1) ◽  
pp. 218-223 ◽  
Author(s):  
Mark R. Harrigan ◽  
Elad I. Levy ◽  
Bernard R. Bendok ◽  
L. Nelson Hopkins
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Scale Score ◽  
Intracranial Hemorrhage ◽  
National Institutes Of Health ◽  
Left Middle Cerebral Artery ◽  
Computed Tomographic ◽  
Left Middle ◽  
Arterial Thrombolysis

Abstract OBJECTIVE AND IMPORTANCE Intra-arterial thrombolysis has been demonstrated to improve recanalization and outcomes among patients with acute ischemic stroke. However, thrombolytic agents have limited effectiveness and are associated with a significant risk of bleeding. Bivalirudin is a direct thrombin inhibitor that has been demonstrated in the cardiology literature to have a more favorable efficacy and bleeding profile than other antithrombotic medications. We report the use of bivalirudin during endovascular treatment of acute stroke, when hemorrhagic complications are not uncommon. CLINICAL PRESENTATION A 71-year-old woman with atrial fibrillation presented with right hemiparesis and aphasia and was found to have a National Institutes of Health Stroke Scale score of 10. Computed tomographic scans revealed no evidence of intracranial hemorrhage, aneurysm, or ischemic stroke. Cerebral angiography revealed thromboembolic occlusion of the superior division of the left middle cerebral artery. INTERVENTION For anticoagulation, a loading dose of bivalirudin was intravenously administered before the interventional procedure, followed by continuous infusion. Attempts to remove the clot with an endovascular snare failed to induce recanalization of the vessel. Bivalirudin was then administered intra-arterially. Immediate postprocedural angiography demonstrated restoration of flow in the left middle cerebral artery. Repeat computed tomographic scans demonstrated no intracranial hemorrhage. The patient's hemiparesis and aphasia were nearly resolved and her National Institutes of Health Stroke Scale score was 2 at the time of her discharge 5 days later. CONCLUSION To our knowledge, this is the first report of the use of bivalirudin for treatment of acute ischemic stroke. Bivalirudin may be a useful agent for intravenous anticoagulation and intra-arterial thrombolysis in this setting.

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