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.

scholarly journals A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rita Orbán-Kálmándi ◽  
István Szegedi ◽  
Ferenc Sarkady ◽  
István Fekete ◽  
Klára Fekete ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intravenous Thrombolysis ◽  
Positive Association ◽  
Clot Lysis ◽  
Term Therapy ◽  
Stroke Severity ◽  
Short Term ◽  
Blood Samples

AbstractThe outcome of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only favorable in ≈ 40% of acute ischemic stroke (AIS) patients. Moreover, in ≈ 6–8% of cases, intracerebral hemorrhage (ICH) develops. We tested whether a modification of clot lysis assay (CLA), might predict therapy outcomes and safety. In this prospective observational study, blood samples of 231 AIS patients, all receiving intravenous rt-PA, were taken before thrombolysis. Cell-free DNA (cfDNA), CLA and CLA supplemented with cfDNA and histones (mCLA) were determined from the blood samples. Stroke severity was determined by NIHSS on admission. ICH was classified according to ECASSII. Short- and long-term outcomes were defined at 7 and 90 days post-event according to ΔNIHSS and by the modified Rankin Scale, respectively. Stroke severity demonstrated a step-wise positive association with cfDNA levels, while a negative association was found with the time to reach 50% lysis (50%CLT) parameter of CLA and mCLA. ROC analysis showed improved diagnostic performance of the mCLA. Logistic regression analysis proved that 50%CLT is a predictor of short-term therapy failure, while the AUC parameter predicts ICH occurrence. A modified CLA, supplemented with cfDNA and histones, might be a promising tool to predict short-term AIS outcomes and post-lysis ICH.

scholarly journals Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel

2020 ◽  
Vol 15 (5) ◽  
pp. 540-554 ◽  
Author(s):  
Adnan I Qureshi ◽  
Foad Abd-Allah ◽  
Fahmi Al-Senani ◽  
Emrah Aytac ◽  
Afshin Borhani-Haghighi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Current Knowledge ◽  
Intravenous Thrombolysis ◽  
Adult Patients ◽  
World Health ◽  
Stroke Patients ◽  
International Panel ◽  
Health Organization ◽  
Tract Infections

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.

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

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.

Nomogram to Predict Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke in an Asian Population.

2021 ◽  
Vol 19 ◽  
Author(s):  
Xiaohua Xie ◽  
Jie Yang ◽  
Lijie Ren ◽  
Shiyu Hu ◽  
Wancheng Lian ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Calibration Curve ◽  
Intravenous Thrombolysis ◽  
Asian Population ◽  
Individual Risk ◽  
Clinical Effects ◽  
Symptomatic Intracranial Hemorrhage

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries Objective: To develop a nomogram to predict the possibility of sICH after IVT in an Asian population. Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The end point was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3%) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95% CI, 1.01–1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95% CI, 1.09–1.35, P < 0.001), and cardioembolism (OR, 3.74; 95% CI, 1.23–11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability [AUC, 0.878; specificity, 87.35%; and sensitivity, 73.81%]. Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95% CI: 0.823–0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects Conclusion: The nomogram consisted of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model’s predictions.

Abstract P253: Readmission in Acute Ischemic Stroke Patients Undergoing Endovascular Treatment

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Saqib Chaudhry ◽  
Ibrahim Laleka ◽  
Zelalem Bahiru ◽  
Hassan S Gill ◽  
Mohammad Rauf Chaudhry ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Stroke Patients ◽  
Factors Associated ◽  
Representative Study ◽  
Post Procedure ◽  
Icd 10 ◽  
Nationally Representative

Background: Recent trials have demonstrated a reduction in death or disability with endovascular treatment in patients with acute ischemic strokes. However, readmission rates and predictors are not known. Objective: To identify rates and factors associated with 30-day readmission after endovascular treatment in ischemic stroke patients. Methods: Nationwide Readmissions Data (NRD) between 2010 and 2017 was utilized to identify endovascular treatment in acute ischemic stroke patients using ICD-9 and ICD-10 codes. We used hierarchical logistic regression model to identify factors associated with 30-day readmissions. Results: Among 17, 562 acute ischemic stroke patients who survived to discharge after endovascular treatment, 2334 (13.29%) were readmitted within 30-days. Age => 65 years (odds ratio [OR]: 1.23, 95% confidence interval [CI]: 1.09 to 1.39, p =0.0005), chronic kidney disease (OR: 1.28, 95%CI: 1.12 to 1.47, p = 0.0004), congestive heart failure (OR: 1.25, 95%CI: 1.13 to 1.39, p <.0001), post procedure intracranial hemorrhage (OR: 1.09, 95%CI: 0.99 to 1.20, p = 0.04) and diabetes mellitus (OR: 1.09, 95%CI: 0.99 to 1.20, p = .09) during the index hospitalization were associated with readmission within 30 days. Conclusion: In this large nationally representative study, nearly one in 10 patients were readmitted within 30 days after discharge in acute ischemic stroke patients undergoing endovascular treatment. Medical comorbidities and post procedure intracranial hemorrhage were associated with 30-day readmission.

Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
The United States ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Increased Risk ◽  
Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

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