ADAMTS13 activity is associated with early neurological improvement in acute ischemic stroke patients treated with intravenous thrombolysis

2019 ◽  
Vol 49 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Anne-Sophie Putzer ◽  
Hans Worthmann ◽  
Gerrit M. Grosse ◽  
Friedrich Goetz ◽  
Jens Martens-Lobenhoffer ◽  
...  
2020 ◽  
Vol 15 (5) ◽  
pp. 540-554 ◽  
Author(s):  
Adnan I Qureshi ◽  
Foad Abd-Allah ◽  
Fahmi Al-Senani ◽  
Emrah Aytac ◽  
Afshin Borhani-Haghighi ◽  
...  

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.


2021 ◽  
Vol 14 ◽  
pp. 175628642110211
Author(s):  
Georgios Magoufis ◽  
Apostolos Safouris ◽  
Guy Raphaeli ◽  
Odysseas Kargiotis ◽  
Klearchos Psychogios ◽  
...  

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.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 347
Author(s):  
Zsuzsa Bagoly ◽  
Barbara Baráth ◽  
Rita Orbán-Kálmándi ◽  
István Szegedi ◽  
Réka Bogáti ◽  
...  

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.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  

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.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mushtaq H Qureshi ◽  
Shayaan M Khan ◽  
Nauman Jahangir ◽  
Ahmed A Malik ◽  
Melissa Freese ◽  
...  

Background: The number of acute ischemic stroke patients who are on both aspirin and clopidogrel treatment at time of acute ischemic event is increasing. There is limited data regarding the safety and efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) treatment in such patients. Methods: We reviewed the medical records and imaging data of consecutive patients with acute ischemic stroke who received IV rt-PA within 4.5 hours of symptom onset. We stratified the patients based on active regular use of antiplatelet medications: monotherapy (aspirin or clopidogrel), combination therapy (aspirin and clopidogrel), and no therapy and compared the rates of symptomatic intracerebral hemorrhage (ICH), neurological improvement (≥4 points in National Institutes of Health Stroke Scale [NIHSS], and favorable outcome (modified Rankin scale [mRS] 0-1) at discharge between the three groups. Results: A total of 88 acute ischemic stroke patients (mean age±SD; 69.88 ±15) were treated with IV rt-PA within the study duration. Of the 88 patients 45 (50.6%), 37 (41.6%), and 52 (58.4) were on monotherapy, combination therapy, or no therapy at time of presentation. The proportion of patients who developed symptomatic ICHs were similar (p=0.8) in monotherapy, combination therapy, and no therapy groups (3.3%, 0.0%, and 4.1%, respectively). The rates of neurological improvement were greater in patients on monotherapy (20%) (p=0.03) followed by combination therapy (11.1%), and no therapy groups (2.0%). There was no significant reduction in the rate of favorable outcome at discharge among patients on combination treatment compared with no treatment (odds ratio 0.8 , 95% confidence interval 0.4-1.8 ) after adjusting for age and initial NIHSS score strata (<10, 10-19, and ≥20). Conclusions: Compared with patients on no antiplatelet treatment, acute ischemic stroke patients who are actively using aspirin and clopidogrel appear to have similar risks and benefits with IV rt-PA treatment.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Leonard L Yeo ◽  
Liang Shen ◽  
Ben Wakerley ◽  
Aftab Ahmad ◽  
Kay W Ng ◽  
...  

Background: Intravenously administered tissue plasminogen activator (IV-TPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Wide variations in the rates and timing of neurological recovery are observed in thrombolyzed patients. While all IV-TPA treated patients are routinely evaluated for neurological recovery at 24-hours, considerable improvement occurs in some cases within 2-hours of treatment initiation. We evaluated whether early neurological improvement at 2-hours after IV-TPA bolus (ENI-2) can predict functional outcomes in thrombolyzed AIS patients at 3-months. Methods: Data for consecutive stroke patients treated with IV-TPA within 4.5 hours of symptom-onset during 2007-2010 were prospectively entered in the thrombolyzed registry maintained at our tertiary care center. Data were collected for demographic characteristics, vascular risk factors, stroke subtypes and blood pressure levels before IV-TPA bolus. National Institute of Health Stroke Scale (NIHSS) scores were obtained before IV-TPA bolus and at 2-hours. ENI-2 was defined as a reduction in NIHSS score by more than 10-points from baseline score or an absolute score of 4-points or less at 2-hours after IV-TPA bolus. Functional outcomes at 3-months were determined by modified Rankin scale (mRS). Data were analyzed by SPSS 19.0. Results: Of the 2238 AIS patients admitted during the study period, 240 (11%) received IV-TPA within 4.5-hours of symptom-onset. Median age was 65yrs (range 19-92), 63% males, median NIHSS 17points (range 3-35) and median onset-to-treatment time 149 minutes. Overall, 122 (50.8%) patients achieved favorable functional outcome (mRS 0-1) at 3-months. Factors associated with favorable outcome at 3-months on univariable analysis were younger age, female gender, presence of atrial fibrillation, baseline NIHSS, onset-to-treatment time (OTT) and ENI-2. However, multivariable analysis demonstrated NIHSS at onset (OR per 1-point increase 0.907, 95%CI 0.848-0.969) and ENI-2 (OR 4.926 95%CI 1.66-15.15) as independent predictors of favorable outcome at 3-months. Conclusion: Early Neurological improvement at 2-hours after IV-TPA bolus is a strong predictor of the functional outcome at 3-months in acute ischemic stroke patients.


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