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 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 Role of some inflammatory biomarkers in prediction of short-term outcome in acute ischemic stroke

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Yosria Abd Al Hameed AlTaweel ◽  
Rania Sanad Nageeb ◽  
Pakinam Mahmoud Metwally ◽  
Ahmed Elsayed Badawy
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Stroke Severity ◽  
Short Term ◽  
Laboratory Assessment ◽  
Term Outcome ◽  
Neutrophil Lymphocyte Ratio ◽  
Short Term Outcome ◽  
Wbc Count

Abstract Background Several factors affect acute ischemic stroke (AIS) outcomes. Objective This study aimed to assess the role of the leukocyte count, neutrophil/lymphocyte ratio (NLR), and c reactive protein (CRP) as early predictors of outcome in AIS patients. Methods This study was conducted on 60 AIS patients. They were subjected to detailed history taking, clinical examination, brain imaging, and laboratory assessment including the CRP, white blood cell (WBC) count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and NLR which is calculated by dividing ANC by ALC. Neurological scales were used to assess the level of consciousness by the Glasgow Coma Scale (GCS) and stroke severity by the National Institute of Health Stroke Scale (NIHSS) at the first 48 h of stroke onset as well as 1 week and 2 weeks later for the assessment of short-term functional neurological outcome. Results Sixty percent of the patients had unfavorable outcomes assessed by the Modified Rankin Scale (mRS). Patients with unfavorable outcomes had higher NIHSS scores. NLR was positively correlated with WBC count, ANC, and CRP. The higher WBC, NLR, and NIHSS, the unfavorable the outcome was. Conclusion The higher WBC, the NLR, and the level of CRP at the onset of AIS, the more severe stroke and the poorer the short-term outcome are expected.

Abstract W P366: Hypothermia Does Not Affect Tissue Plasminogen Activator Activity in Acute Ischemic Stroke Patients as Measured by Thromboelastography

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Joancy M Archeval-Lao ◽  
Hope Moser ◽  
Stephen A Riney ◽  
Jorge Kawano-Castillo ◽  
Stephanie A Parker ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Venous Blood ◽  
Clot Formation ◽  
Clot Lysis ◽  
Stroke Patients ◽  
Blood Samples ◽  
Lytic Effect ◽  
Tissue Plasminogen ◽  
Coagulation Status

Background: Currently, t-PA is the only FDA approved treatment for acute ischemic stroke (AIS). Supplementing t-PA with therapeutic hypothermia is being evaluated, but cooler temperatures may affect the enzymatic activity of t-PA. Thromboelastography (TEG) determines coagulation status in whole blood, and has detected hypercoagulability in AIS patients compared to healthy controls. Using TEG, we evaluated the effect of variable degrees of hypothermia on clot formation and lysis in AIS patients receiving t-PA. Methods: Between June 2012 -July 2013, venous blood from 18 AIS patients receiving t-PA within 4.5 hours of symptom onset was collected prior to and 10 minutes after t-PA bolus. Blood samples were analyzed by TEG at 30°C, 33°C, and 37°C. The variables of interest were R (initiation of clot formation), K (speed of clot strengthening), Angle α (rate of clot formation), and LY30 (percentage of clot lysis over 30 minutes) (see figure). All statistical analyses were performed using SAS 9.3. Results: Baseline R averaged 6.0, 5.6, and 4.6 minutes at 30°C, 33°C, and 37°C (p=0.02),K averaged 2.5, 2.3, and 1.4 (p=0.01),and Angle averaged 59.1, 62.4, and 69.3(p=0.01), indicating slower clotting at lower temperatures. Post t-PA LY30 averaged 93.9, 93.9, 89.8 (p= 0.61, N=18) indicating no effect on t-PA lytic activity at lower temperatures. Conclusions: Our data suggest that hypothermia progressively slows clot formation in AIS patients but has no effect on the lytic effect of t-PA as measured by TEG.

scholarly journals Elevated plasma D-dimer level is associated with short-term poor outcome in patients with acute ischemic stroke: a prospective, observational study

2019 ◽  
Author(s):  
Tao Yao ◽  
Bo-Lin Tian ◽  
Gang Li ◽  
QIN CUI ◽  
Cui-fang Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Clinical Laboratory ◽  
Predictive Marker ◽  
Stroke Severity ◽  
Elevated Plasma ◽  
Short Term ◽  
Poor Outcome ◽  
D Dimer

Abstract Background Elevated level of D-dimer increases the risk of ischemic stroke, stroke severity and progression of stroke status, but the association between D-dimer and functional outcome is unclear. The aim of this study is to investigate whether Plasma D-dimer level is a determinant of short-term poor functional outcomes in patients with acute ischemic stroke (AIS). Methods This prospective study included 877 patients with AIS provided plasma D-dimer level after stroke onset. Patients were categorized per D-dimer level: Quartile 1(≤0.24 mg /L), Quartile 2 (0.25–0.56 mg /L), Quartile 3 (0.57–1.78 mg /L), and Quartile 4 (>1.78mg /L). Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale (mRS). Results Of 877 patients were included (mean age, 64 years; male, 68.5%), poor outcome was present in 302 (34.4%) patients. After adjustment for potential confounding variables, higher D-dimer level on admission was associated with poor outcome (adjusted odds ratio [aOR] 2.257, 95% CI1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a D-dimer level ≥0.315 mg/L for pour outcome [area under the ROC curve (AUC) 0.657; sensitivity 83.8%; specificity 41.4%]. Conclusion Elevated plasma D-dimer level on admission was significantly associated with increased poor outcome after admission for AIS, suggesting the potential role of D-dimer as a predictive marker for short-term poor outcomes in patients with AIS.

scholarly journals TRIAGE-STROKE: Treatment strategy In Acute larGE vessel occlusion: Prioritize IV or endovascular treatment—A randomized trial

2019 ◽  
Vol 15 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Anne Behrndtz ◽  
Søren P Johnsen ◽  
Jan B Valentin ◽  
Martin F Gude ◽  
Rolf A Blauenfeldt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Hospital Setting ◽  
Intravenous Thrombolysis ◽  
Large Vessel ◽  
Stroke Severity ◽  
Study Results ◽  
Primary Stroke Center ◽  
Stroke Center

Rationale For patients with acute ischemic stroke and large vessel occlusions, intravenous thrombolysis and endovascular therapy are standard of care, but the effect of endovascular therapy is superior to intravenous thrombolysis. If a severe stroke with symptoms indicating large vessel occlusions occurs in the catchment area of a primary stroke center, there is equipoise regarding optimal transport strategy. Aim For patients presenting with suspected large vessel occlusions (PASS ≥ 2) and a final diagnosis of acute ischemic stroke, we hypothesize that bypassing the primary stroke center will result in an improved 90-day functional outcome. Sample size We aim to randomize 600 patients, 1:1. Design A national investigator-driven, multi-center, randomized assessor-blinded clinical trial. The Prehospital Acute Stroke Severity Scale has been developed. It identifies most patients with large vessel occlusions in the pre-hospital setting. Patients without a contraindication for intravenous thrombolysis are randomized to either transport directly to a comprehensive stroke centers for intravenous thrombolysis and of endovascular therapy or to a primary stroke center for intravenous thrombolysis and subsequent transport to a comprehensive stroke centers for of endovascular therapy, if needed. Outcomes The primary outcome will be the 90-day modified Rankin Scale score (mRS) for all patients with acute ischemic stroke. Secondary outcomes include 90-day mRS for all randomized patients, all patients with ischemic stroke but without large vessel occlusions, and patients with hemorrhagic stroke. The safety outcomes include severe dependency or death and time to intravenous thrombolysis for ischemic stroke patients. Discussion Study results will influence decision making regarding transport strategy for patients with suspected large vessel occlusions.

Abstract 58: The Iscore Predicts Efficacy Of Thrombolytic Therapy For Acute Ischemic Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Gustavo Saposnik ◽  
Jiming Fang ◽  
Moira Kapral ◽  
Jack Tu ◽  
Muhammad Mamdani ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Clinical Response ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Neurological Deterioration ◽  
Stroke Severity ◽  
Risk Of Death ◽  
Poor Outcome

Background: The iScore is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. It includes demographics, stroke severity and subtype, vascular risk factors, cancer, renal failure, and pre-admission functional status. Limited information is available to predict the clinical response after intravenous thrombolytic therapy (tPA). Objective: To determine the ability of the iScore to predict the clinical response and risk of hemorrhagic transformation after tPA. Methods: We applied the iScore ( www.sorcan.ca/iscore ) to patients presenting with an acute ischemic stroke at 11 stroke centres in Ontario, Canada, between 2003 and 2008, identified from the Registry of the Canadian Stroke Network (RCSN). We compared outcomes between patients receiving and not receiving tPA adjusting for differences in baseline characteristics through matching by propensity scores. Three groups were defined a priori as per the iScore (low risk 180). Outcome Measures: Poor outcome, the primary outcome measure, was defined as disability at discharge or death at 30 days. Secondary outcomes included disability at discharge, neurological deterioration and intracranial hemorrhage (any type and symptomatic). Results: Among 12,686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Overall, 589 tPA patients were matched with 589 non-tPA patients (low iScore risk), 682 tPA were matched with 682 non-tPA patients (medium iScore risk) and 419 tPA patients were matched with 419 non-tPA patients (high iScore risk). There was good matching in all three groups. Higher iScore was associated with poor functional outcome in both the tPA and non-tPA groups (p<0.001). Among those with low and medium iScore risk, tPA use was associated with lower risk of poor outcome (Low iScore RR 0.74; 95%CI 0.67-0.84; medium iScore RR 0.88; 95%CI 0.84-0.93). There was no difference in clinical outcomes between matched patients receiving and not receiving tPA in the highest iScore group (RR 0.97; 95%CI 0.94-1.01). Similar results were observed for disability at discharge and length of stay. The incident risk of neurological deterioration and hemorrhagic transformation (any or symptomatic) increased with the iScore risk ( Figure ). Conclusion: The iScore appears to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not benefit from tPA and have higher risk of hemorrhagic transformation, though this finding should be validated independently (underway) before clinical use.

Abstract W P160: Elevated Lipoprotein A Levels Predict Worse Short-term Outcomes in Acute Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Alyana A Samai ◽  
Dominique J Monlezun ◽  
Amir Shaban ◽  
Alexander George ◽  
Janelle Cyprich ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Serum Levels ◽  
Stroke Severity ◽  
Short Term ◽  
Poor Functional Outcome ◽  
Lipoprotein A ◽  
Stroke Registry ◽  
History Of

Background: Lipoprotein A (Lp(a)) is a risk factor for vascular disease; however, few studies have examined the relationship between serum levels of Lp(a) and patient outcomes in acute ischemic stroke (AIS). In this study, we sought to assess whether AIS patients with elevated Lp(a) levels exhibit characteristic differences in stroke severity, in-hospital complications, and short-term outcomes as compared to patients with normal Lp(a) levels. Methods: From our prospective stroke registry, patients consecutively admitted and diagnosed with AIS 07/2008-10/2013 were included if Lp(a) levels were measured during admission. Regressions, adjusting for key covariates, analyzed outcomes in patients with elevated (+) and severely elevated (++) Lp(a) with respect to normal (-) Lp(a). The primary outcome was poor functional outcome (modified Rankin Scale > 2) on discharge. Results: Among the 1,453 patients in our stroke registry, 159 patients met our inclusion criteria; 24 patients (15.1%) were in the +Lp(a) group and 37 patients (23.3%) in the ++Lp(a) group. After adjustment for total cholesterol, LDL, HDL, and triglycerides, patients with ++Lp(a) were more than twice as likely to experience poor functional outcome (OR=2.48, 95% CI 1.0781-5.7231, p=0.033) as those with -Lp(a). Adjusting for age, NIHSS baseline, history of diabetes, admission glucose level, and tPA administration, patients with ++Lp(a) were more than 2.5 times more likely to experience poor functional outcome (OR=2.59, 95% CI 1.0129-6.6282, p=0.047) as compared to those with -Lp(a). Conclusions: Lp(a) elevation predicts higher odds of poor functional outcomes for patients with AIS compared to patients with normal levels. Our findings support the utility of Lp(a) level as a clinically useful biomarker in the development of patient risk profiles.

Abstract TMP66: Intravenous Thrombolysis is Associated with Lower Risk of Severe Disability and Death among SPAN-100 Positive Acute Ischemic Stroke Patients

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Bruce Ovbiagele ◽  
Mat Reeves ◽  
S. C Johnston ◽  
Philip Bath ◽  
Gustavo Saposnik ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Treatment Effect ◽  
Lower Risk ◽  
Intravenous Thrombolysis ◽  
Severe Disability ◽  
Neurological Deficits ◽  
Stroke Severity ◽  
Low Probability

BACKGROUND: Clinicians are cautious about administering intravenous thrombolysis (tPA) to acute ischemic stroke (AIS) patients who are very elderly and/or have severe neurological deficits. The Stroke Prognostication using Age and NIHSS (SPAN) index combines age plus stroke severity (NIHSS) to create a binary measure (≥ 100 vs. < 100) to predict clinical outcome. We evaluated the effectiveness of tPA by SPAN-100 index status among a large sample of AIS patients. METHODS: Data on 7140 AIS participants in the Virtual International Stroke Trials Archive (VISTA) collaboration. Outcome measures included severe disability or death at 3 months (defined as modified Rankin Scale {mRS} 4-6) and death alone. Effect of tPA on outcomes was assessed using multivariable logistic regression adjusting for SPAN-100 status. RESULTS: Among all patients, 743 (10.5%) were SPAN-100 positive (≥ 100), and 2731 (38.2%) received tPA treatment. Of those treated with tPA, SPAN-100 positive patients were more likely to experience severe disability or death (73.2% vs. 36.3%; p<0.0001) or death alone (33.6% vs. 11.4%; p<0.0001) than SPAN-100 negative patients. However, among SPAN-100 positive patients, tPA was associated with a significantly lower risk of severe disability and death, and tPA had a significantly greater treatment effect among SPAN-100 positive vs. SPAN-100 negative patients (Table). Logistic regression analyses showed significant interactions between SPAN-100 status and tPA (mRS of 4-6 <0.001; death 0.029) confirming that tPA had a greater treatment effect among SPAN-100 positive vs. SPAN-100 negative patients, even after adjustment for age and NIHSS. CONCLUSIONS: Despite the low probability of a favorable outcome, tPA reduces the risk of severe disability and death among SPAN-100 positive AIS patients. SPAN-100 index can be readily used in emergency care settings to identify high risk AIS patients who may be less prone to catastrophic outcomes after tPA treatment.

Sign in / Sign up

Export Citation Format

Share Document