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Medical Science Monitor Basic Research Mar 2017BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the... (Meta-Analysis)
Meta-Analysis Review
Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review.
BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusive. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating the association of coagulation activation, fibrinolytic, and endothelial function with occurrence of AF and clinical adverse events. A comprehensive subgroup analysis and meta-regression was performed to explore potential sources of heterogeneity. RESULTS A literature search of major databases retrieved 1703 studies. After screening, a total of 71 studies were identified. Pooled analysis showed the association of coagulation markers (D-dimer (weighted mean difference (WMD) =197.67 and p<0.001), fibrinogen (WMD=0.43 and p<0.001), prothrombin fragment 1-2 (WMD=0.53 and p<0.001), antithrombin III (WMD=23.90 and p=0.004), thrombin-antithrombin (WMD=5.47 and p=0.004)); fibrinolytic markers (tissue-type plasminogen activator (t-PA) (WMD=2.13 and p<0.001), plasminogen activator inhibitor (WMD=11.44 and p<0.001), fibrinopeptide-A (WMD=4.13 and p=0.01)); and endothelial markers (von Willebrand factor (WMD=27.01 and p<0.001) and soluble thrombomodulin (WMD=3.92 and p<0.001)) with AF. CONCLUSIONS The levels of coagulation, fibrinolytic, and endothelial markers have been reported to be significantly higher in AF patients than in SR patients.
Topics: Atrial Fibrillation; Biomarkers; Blood Coagulation Factors; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Stroke; Thromboembolism; Tissue Plasminogen Activator
PubMed: 28360407
DOI: 10.12659/MSMBR.902558 -
Seminars in Thrombosis and Hemostasis Jul 2019Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and... (Meta-Analysis)
Meta-Analysis
Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (PubMed), Scopus, Web of Science, ScienceDirect, Lilacs, Cinahl, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Among 5,278 studies identified, 32 were included in the final synthesis, and these included 485 patients with mild cognitive impairment, 568 with vascular dementia (VD), 1,781 with AD, and 2,855 participants without dementia. AD patients had increased plasma von Willebrand factor (VWF) (standardized mean difference [SMD]: 2.53; 95% confidence interval [CI]: 0.10-4.95), D-dimer (SMD: 0.50; 95% CI: 0.35-0.66), plasminogen activator inhibitor-1 (SMD: 3.34; 95% CI: 1.01-5.67), thrombomodulin (SMD: 1.08; 95% CI: 0.53-1.62), and homocysteine levels (SMD: 0.65; 95% CI: 0.15-1.15). In contrast, the VD group showed increased fibrinogen levels (SMD: 0.77; 95% CI: 0.13-1.41), activated factor VII (SMD: 0.36; 95% CI: 0.05-0.67), factor VIII (SMD: 0.57; 95% CI: 0.22-0.91), VWF (SMD: 2.34; 95% CI: 0.38-4.29), D-dimer (SMD: 1.14; 95% CI: 0.51-1.78), and homocysteine (SMD: 2.17; 95% CI: 1.67-2.68). AD showed an elevation in some markers of endothelial dysfunction, whereas VD presented mostly an involvement of coagulation cascade components.
Topics: Alzheimer Disease; Dementia; Hemostatics; Humans
PubMed: 31096308
DOI: 10.1055/s-0039-1688444 -
European Journal of Neurology Jun 2021According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms.
METHODS
We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects.
RESULTS
We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies).
CONCLUSIONS
This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.
Topics: Adult; Fibrinolytic Agents; Humans; Ischemic Stroke; Prospective Studies; Retrospective Studies; Risk Factors; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33772987
DOI: 10.1111/ene.14839 -
Frontiers in Immunology 2018Plasminogen activator inhibitor-1 (PAI-1), a crucial regulator of fibrinolysis, is increased in sepsis, but its values in predicting disease severity or mortality... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Plasminogen activator inhibitor-1 (PAI-1), a crucial regulator of fibrinolysis, is increased in sepsis, but its values in predicting disease severity or mortality outcomes have been controversial. Therefore, we conducted a systematic review and meta-analysis of its predictive values in sepsis.
METHODS
PubMed and Embase were searched until August 18, 2017 for studies that evaluated the relationships between PAI-1 levels and disease severity or mortality in sepsis.
RESULTS
A total of 112 and 251 entries were retrieved from the databases, of which 18 studies were included in the final meta-analysis. A total of 4,467 patients (36% male, mean age: 62 years, mean follow-up duration: 36 days) were analyzed. PAI-1 levels were significantly higher in non-survivors than survivors [odds ratios (OR): 3.93, 95% confidence interval (CI): 2.31-6.67, < 0.0001] and in patients with severe sepsis than in those less severe sepsis (OR: 3.26, 95% CI: 1.37-7.75, = 0.008).
CONCLUSION
PAI-1 is a significant predictor of disease severity and all-cause mortality in sepsis. Although the predictive values of PAI-1 reached statistical significance, the clinical utility of PAI-1 in predicting outcomes will require carefully designed prospective trials.
Topics: Biomarkers; Humans; Mortality; Odds Ratio; Plasminogen Activator Inhibitor 1; Prognosis; Sepsis; Severity of Illness Index
PubMed: 29967603
DOI: 10.3389/fimmu.2018.01218 -
Journal of Clinical Medicine Nov 2018The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of... (Review)
Review
AIM
The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation.
METHODS
An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation.
RESULTS
A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) ( = 0.04), re-transplantation rate ( = 0.0001), and no increased requirement of blood transfusion ( = 0.16) with a better one year graft survival ( = 0.02).
CONCLUSIONS
To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.
PubMed: 30413051
DOI: 10.3390/jcm7110425 -
Molecular Human Reproduction Mar 2013The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic... (Meta-Analysis)
Meta-Analysis Review
The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I(2) statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR = 1.36, 95% CI: 1.13-1.64, P = 0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I(2) = 20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.
Topics: Alleles; Female; Genes, Recessive; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Mutagenesis, Insertional; Odds Ratio; Plasminogen Activator Inhibitor 1; Pre-Eclampsia; Pregnancy; Promoter Regions, Genetic; Sequence Deletion
PubMed: 23180602
DOI: 10.1093/molehr/gas056 -
Shock (Augusta, Ga.) Apr 2020Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the importance of timely diagnosis for sepsis treatment, we conducted this systematic review and meta-analysis to evaluate the value of suPAR diagnosis and prognosis for sepsis.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies, which reported the value of suPAR diagnosis and/or prognosis in patients with sepsis.
RESULTS
A total of 30 studies involving 6,906 patients were included. Sensitivity and specificity of suPAR for diagnosing sepsis were 0.76 [95% confidence interval (CI), 0.63-0.86] and 0.78 (95% CI, 0.72-0.83), respectively. The area under the summary receiver-operating characteristic curve (AUC) was 0.83 (95% CI, 0.80-0.86). Pooled sensitivity and specificity for predicting mortality were 0.74 (95% CI, 0.67-0.80) and 0.70 (95% CI, 0.63-0.76), respectively, with AUC of 0.78 (95% CI, 0.74-0.82). In addition, AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was 0.81 (95% CI, 0.77-0.84), and the sensitivity and specificity were 0.67 (95% CI, 0.58-0.76) and 0.82 (95% CI, 0.73-0.88), respectively.
CONCLUSION
suPAR is a feasible biomarker for timely diagnosis and prognosis of sepsis. Compared with effective value of procalcitonin (PCT) identified by previous meta-analysis, suPAR has similar clinical guiding value, whereas suPAR exhibits higher specificity, which can facilitate the deficiencies of PCT. suPAR also shows a diagnostic value in differentiating sepsis from SIRS. Considering the lack of biomarkers for sepsis and the similar clinical value of suPAR and PCT, suPAR should be considered as a biomarker in clinical practice for sepsis.
Topics: Biomarkers; Humans; Predictive Value of Tests; Prognosis; Receptors, Urokinase Plasminogen Activator; Sepsis
PubMed: 31490358
DOI: 10.1097/SHK.0000000000001434 -
Atherosclerosis May 2015The aim of this systematic review was to perform a meta-analysis of randomized controlled trials (RCTs) examining the efficacy of fibrate therapy in reducing plasma... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review was to perform a meta-analysis of randomized controlled trials (RCTs) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 (PAI-1).
METHODS
Scopus and MEDLINE databases were searched (up to October 15, 2014) to identify RCTs investigating whether fibrates lower plasma PAI-1 concentration or activity. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential moderators on the estimated effect sizes.
RESULTS
A total of 14 RCTs examining the effects of gemfibrozil (6 trials), bezafibrate (4 trials), and fenofibrate (5 trials) were included. Meta-analysis suggested that fibrate therapy did not significantly reduce plasma PAI-1 concentration (weighed mean difference [WMD]: -11.39 ng/mL, 95% CI: -26.64, 3.85, p=0.143) or activity (WMD: 2.02 U/mL, 95% CI: -0.87, 4.90, p=0.170). These results remained unchanged after subgroup analysis according to duration of treatment (<12 and ≥12 weeks) and type of fibrate administered (fenofibrate, bezafibrate or gemfibrozil). The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis.
CONCLUSION
This meta-analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1.
Topics: Biomarkers; Cardiovascular Diseases; Down-Regulation; Dyslipidemias; Fibric Acids; Humans; Plasminogen Activator Inhibitor 1; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 25828270
DOI: 10.1016/j.atherosclerosis.2015.03.016 -
Journal of Vascular Surgery Feb 2020The initial treatment of patients with acute limb ischemia (ALI) remains undefined. The aim of this article was to compare the safety and effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The initial treatment of patients with acute limb ischemia (ALI) remains undefined. The aim of this article was to compare the safety and effectiveness of catheter-driven thrombolysis (CDT) with surgical revascularization and evaluate the various fibrinolytic agents, endovascular, and pharmacochemical approaches that aim for thrombectomy.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies on the management of ALI by means of surgical or endovascular recanalization, returning 520 studies. All randomized, controlled trials, nonrandomized prospective, and retrospective studies were included comparing treatment of ALI.
RESULTS
Twenty-five studies, investigating a total of 4689 patients, were included for meta-analysis spread across nine different comparisons. No differences were found in limb salvage between thrombectomy and thrombolysis. More major vascular events were seen in the thrombolysis group (6.5% compared with 4.4% in the surgically treated group; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13-0.87; P = .02; I = 20%). Comparable limb salvage was found for high- and low-dose recombinant tissue plasminogen activator (r-tPA). No significant differences were found in major vascular event between low r-tPA (14%) and high r-tPA (10.5%; P = .13). The 30-day limb salvage rate was 79.7% for r-tPA treatment and 60.4% for streptokinase (OR, 3.14; 95% CI, 1.26-7.85; P = .01; I = 0%). AngioJet showed more limb salvage at 6 months compared with r-tPa (OR, 2.21; 95% CI, 1.17-4.18; P = .01; I = 0%).
CONCLUSIONS
Both CDT and surgery have comparable limb salvage rates in patients with ALI; however, CDT is associated with a higher risk of hemorrhagic complications. No conclusions can be drawn regarding the risk of hemorrhagic complications regarding thrombolytic therapy by means of r-tPA, streptokinase, or urokinase. Insufficient data are available to conclude the preference of using a hybrid approach, ultrasound-accelerated CDT, heated r-tPA. or novel endovascular (rheolytical) thrombectomy systems. Future trials regarding ALI need to be constructed carefully, ensuring comparable study groups, and should follow standardized practices of outcome reporting.
Topics: Acute Disease; Endovascular Procedures; Fibrinolytic Agents; Humans; Ischemia; Limb Salvage; Lower Extremity; Tissue Plasminogen Activator; Vascular Surgical Procedures
PubMed: 31353270
DOI: 10.1016/j.jvs.2019.05.031 -
Journal of Clinical Neuroscience :... Dec 2022Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS.
METHODS
The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021.
RESULTS
A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I = 0 %; P = 0.30).
CONCLUSION
Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.
Topics: Humans; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Urokinase-Type Plasminogen Activator
PubMed: 36274296
DOI: 10.1016/j.jocn.2022.09.015