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Journal of Clinical Medicine Feb 2022Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In... (Review)
Review
Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In this systematic review, the role of inflammation in subjective tinnitus was studied. Nine animal and twenty human studies reporting inflammatory markers in both humans and animals with tinnitus were included. It was established that TNF-α and IL-1β are increased in tinnitus, and that microglia and astrocytes are activated as well. Moreover, platelet activation may also play a role in tinnitus. In addition, we elaborate on mechanisms of inflammation in tinnitus, and discuss potential treatment options targeting inflammatory pathways.
PubMed: 35207270
DOI: 10.3390/jcm11041000 -
Thrombosis and Haemostasis Apr 2016Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large... (Meta-Analysis)
Meta-Analysis Review
Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data.
Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 µM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel.
Topics: Age Factors; Cardiovascular Diseases; Clopidogrel; Humans; Platelet Aggregation; Platelet Function Tests; Predictive Value of Tests; Risk; Ticlopidine
PubMed: 26607655
DOI: 10.1160/TH15-09-0742 -
Thrombosis Research Nov 2023Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained....
INTRODUCTION
Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained. Platelets play a key role in CVD and may be affected by regular exercise training. We aimed to systematically summarise studies investigating the effect of regular exercise training on platelet function in patients with CVD and in healthy individuals.
METHODS
Studies were identified by PubMed, Embase and Web of Science May 16, 2022. We selected studies investigating markers of platelet function in relation to regular exercise training in patients with CVD and in healthy individuals. Regular exercise was defined as exercise training for four weeks or more.
RESULTS
Of the included studies, 11 investigated patients with CVD and 29 were on healthy individuals. Studies were heterogeneous regarding design, study population and methodology, and the results were ambiguous. In total, 52 different markers of platelet function were investigated with platelet aggregation, soluble P-selectin, and thromboxane B (TXB) as the most frequently examined. When evaluating between-group changes after regular exercise, two studies found a reduced platelet aggregation in the exercise group whilst three studies did not find a difference between groups. With respect to TXB, three studies reported a reduction and two studies an increase in the exercise group. There were no between-group differences in the seven studies examining soluble P-selectin.
CONCLUSION
Regular exercise training has no clear impact on platelet function in patients with CVD or healthy individuals.
PROSPERO REGISTRATION
CRD42022350539.
Topics: Humans; P-Selectin; Cardiovascular Diseases; Platelet Aggregation; Blood Platelets; Exercise
PubMed: 36609119
DOI: 10.1016/j.thromres.2022.12.017 -
Journal of the American Heart... May 2016A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still... (Review)
Review
BACKGROUND
A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still undefined.
METHODS AND RESULTS
We searched MEDLINE via PubMed and Cochrane database between 1965 and 2015. All observational clinical studies and interventional trials reporting 1-year incidence of MI in AF were included. We also discussed pathophysiological mechanisms, predictors, and therapeutic approaches to reduce the risk of MI in AF. Twenty-one observational studies and 10 clinical trials were included. The annual rate of MI in observational studies including AF patients ranged from 0.4% to 2.5%. Higher rates of MI were reported in AF patients with stable coronary artery disease (11.5%/year), vascular disease (4.47%/year), heart failure (2.9%/year), and in those undergoing coronary artery interventions (6.3%/year). However, lower annual rates have been described in AF patients from Eastern countries (0.2-0.3%/year), and in those enrolled in clinical trials (from 0.4 to 1.3%/year).
CONCLUSIONS
AF patients had a significant residual risk of MI despite anticoagulant treatment. Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF. Identification of high-risk AF patients is a needed first step to develop cost-effective approaches for prevention. A new score, the 2MACE score, has been recently developed to stratify MI risk in AF, and may help not only in allocating resources to high-risk groups, but also in design of studies examining novel therapies for prevention of MI in AF.
Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Heart Failure; Humans; Incidence; Myocardial Infarction; Myocardial Revascularization; Risk Factors; Vascular Diseases
PubMed: 27208001
DOI: 10.1161/JAHA.116.003347 -
Seminars in Thrombosis and Hemostasis Apr 2024Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in... (Meta-Analysis)
Meta-Analysis
Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count ( = 90), platelet indices ( = 19), and platelet function/activation markers ( = 13) in patients with solid cancers ( = 61), hematological cancers ( = 17), or mixed cancer types ( = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19-1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far.
Topics: Adult; Humans; Thrombosis; Platelet Count; Venous Thrombosis; Neoplasms; Biomarkers
PubMed: 36921613
DOI: 10.1055/s-0043-1764381 -
Clinical Chemistry and Laboratory... Apr 2024Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes. Indeed, altered platelet turnover, thrombotic events, and changes in thrombopoietin levels in systemic inflammation have been reported, but thrombopoietin-levels in sepsis and septic-shock have not yet been systematically evaluated. We therefore performed a meta-analysis of thrombopoietin (TPO)-levels in patients with sepsis.
METHODS
Two independent reviewers screened records and full-text articles for inclusion. Scientific databases were searched for studies examining thrombopoietin levels in adult sepsis and septic-shock patients until August 1st 2022.
RESULTS
Of 95 items screened, six studies met the inclusion criteria, including 598 subjects. Both sepsis and severe sepsis were associated with increased levels of thrombopoietin (sepsis vs. control: standardized mean difference 3.06, 95 % CI 1.35-4.77; Z=3.50, p=0.0005) (sepsis vs. severe sepsis: standardized mean difference -1.67, 95 % CI -2.46 to -0.88; Z=4.14, p<0.0001). TPO-levels did not show significant differences between severe sepsis and septic shock patients but differed between sepsis and inflammation-associated non-septic controls. Overall, high heterogeneity and low sample size could be noted.
CONCLUSIONS
Concluding, increased levels of thrombopoietin appear to be present both in sepsis and severe sepsis with high heterogeneity but thrombopoietin does not allow to differentiate between severe sepsis and septic-shock. TPO may potentially serve to differentiate sepsis from non-septic trauma and/or tissue damage related (systemic) inflammation. Usage of different assays and high heterogeneity demand standardization of methods and further large multicenter trials.
Topics: Adult; Humans; Shock, Septic; Thrombopoietin; Sepsis
PubMed: 38037809
DOI: 10.1515/cclm-2023-0792 -
European Journal of Vascular and... Jan 2022Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.
OBJECTIVE
Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease.
METHODS
A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS
There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes.
CONCLUSION
ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.
Topics: Cause of Death; Clopidogrel; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Activation; Platelet Function Tests; Postoperative Complications; Postoperative Hemorrhage; Purinergic P2 Receptor Antagonists; Treatment Outcome
PubMed: 34844834
DOI: 10.1016/j.ejvs.2021.09.026 -
Frontiers in Immunology 2024Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis.
METHODS
Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023.
RESULTS
Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines.
CONCLUSION
Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.
Topics: Humans; Anaphylaxis; Arachidonic Acid; Proteomics; Allergens; Biomarkers
PubMed: 38384462
DOI: 10.3389/fimmu.2024.1328212 -
Platelets Jun 2007The Platelet Function Analyzer (PFA-100) is increasingly being used in the workup of patients with a bleeding diathesis. A profound knowledge of the possible diagnostic... (Meta-Analysis)
Meta-Analysis Review
Diagnostic performance of the platelet function analyzer (PFA-100) for the detection of disorders of primary haemostasis in patients with a bleeding history-a systematic review and meta-analysis.
The Platelet Function Analyzer (PFA-100) is increasingly being used in the workup of patients with a bleeding diathesis. A profound knowledge of the possible diagnostic performance of this test is essential in order to make sound clinical decisions based on its results. It was the aim of this study to systematically review the published literature and provide valid estimates of the diagnostic performance of the PFA-100 for detecting disorders of primary haemostasis in newly presenting patients with a bleeding diathesis. A comprehensive literature search was performed for studies published between January 1994 and February 2006. Studies were eligible for the systematic review if they provided data supposed to be applicable to the determination of the diagnostic performance of the PFA-100. Furthermore, they were included in a meta-analysis if study reporting allowed calculation of sensitivity and specificity and if study quality ensured minimized biases of these estimates for the described clinical setting. Pooled weighted sensitivity, specificity and diagnostic odds ratio were calculated applying random effects modelling and constructing summary operator characteristic curves. This was done separately for the available test modifications using either collagen/epinephrine (PFA-EPI) or collagen/adenosine-diphosphate (PFA-ADP) for platelet activation. Thirty-six articles were included in the systematic review. Six studies met our eligibility criteria for a meta-analysis. The major reason for exclusion from the meta-analysis was a case-control design. A total of 1486 and 1259 patients were included in the meta-analysis of the diagnostic performance of the PFA-EPI and PFA-ADP, respectively. Pooled weighted sensitivity and specificity of the PFA-EPI/PFA-ADP in detecting a disorder of primary haemostasis were: 82.5/66.9% (95%-confidence interval (95%-CI): 76.0-88.9%/57.9-75.9%), and 88.7/85.5% (95%-CI: 84.3-93.1%/82.0-89.1%). 83/75% of patients with a positive PFA-EPI/PFA-ADP result do have a disorder of primary haemostasis whereas 88/79% with a negative PFA-EPI/PFA-ADP result do not. The PFA-EPI appeared to have a higher sensitivity and better predictive values than the PFA-ADP in detecting disorders of primary haemostasis, although a rigorous gold standard definition for a disorder of primary haemostasis, particularly for platelet disorders, was not applied in most studies. The majority of the studies lacked important requirements for quality and reporting, precluding a more precise and definitive characterization of the clinical utility of the PFA-100. This emphasizes the need for an evidence-based critical appraisal of diagnostic studies in haemostasis research in order to promote the conducting of studies that produce clinically relevant results.
Topics: Blood Platelet Disorders; Hemostasis; Humans; Platelet Function Tests; ROC Curve
PubMed: 17538845
DOI: 10.1080/09537100601100366 -
American Heart Journal Sep 2010A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates.
METHODS
Relevant observational studies published between January 2003 and February 2010 were searched that presented intent-to-treat analyses on the clinical relevance of HPR measured with an adenosine diphosphate (ADP)-specific platelet function assay. The main outcome measures were cardiovascular (CV) death, definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and a composite end point of reported ischemic events. The outcome parameters were pooled with the random-effect model via generic inverse variance weighting.
RESULTS
Twenty studies comprising a total number of 9,187 patients qualified. High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI, ST, and the composite end point of reported ischemic events (odds ratios [95% CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P < .00001 for all cases). According to the meta-analysis, patients with HPR had a 3.4-fold higher risk for CV death compared with patients with normal ADP reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P < .00001). Although there were large differences in the methodology as well as in the definition of HPR between studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2): 0%, 0%, and 12%, respectively; P = not significant for all cases).
CONCLUSIONS
High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet function assay, is a strong predictor of CV death, MI, and ST in patients after percutaneous coronary intervention.
Topics: Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Humans; Intention to Treat Analysis; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Systems; Predictive Value of Tests; Prognosis; Stents; Thrombosis; Ticlopidine
PubMed: 20826265
DOI: 10.1016/j.ahj.2010.06.004