-
Atherosclerosis Jun 2015The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine,... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of P2Y12 inhibitors according to diabetes, age, gender, body mass index and body weight: systematic review and meta-analyses of randomized clinical trials.
OBJECTIVE
The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine, prasugrel, ticagrelor, and cangrelor according to diabetes status, age, gender, body mass index, and body weight.
METHODS
Randomized clinical trials (RCTs) of P2Y12 inhibitors reporting information on cardiovascular disease (defined as myocardial infarction, stroke, or cardiovascular death) and bleeding (defined as any bleeding) events among the subgroups diabetes and non-diabetes, age ≥65 and <65 year-old, men and women, body mass index ≥30 and <30 kg/m(2), and body weight ≥60 and <60 kg, were identified in Medline, Embase, Web of Science, and Cochrane Library on August 31st, 2014. For each inhibitor, random-effects meta-analyses were used to estimate the ratio of relative risks (rRR) for cardiovascular and bleeding events among patient subgroups.
RESULTS
Twenty distinct RCTs (233 285 participants, 21 323 cardiovascular and 5183 bleeding events) were identified. Cardiovascular risk reduction with clopidogrel did not significantly differ according to diabetes (rRR: 1.04; 95% CI: 0.95 to 1.13; p = 0.395), age (0.98; 0.88 to 1.09; p = 0.347), gender (0.97; 0.90 to 1.04; p = 0.382), or body mass index (1.11, 0.95 to 1.31; p = 0.191). Results for other inhibitors were comparable, although available data were sparse. Limited data on bleeding events were available.
CONCLUSION
Data from RCTs did not show a different cardiovascular efficacy of clopidogrel in diabetes mellitus and other clinically relevant subgroups. Limited information was available on the efficacy and safety of other P2Y12 inhibitors in specific subgroups.
Topics: Age Factors; Aged; Blood Platelets; Body Mass Index; Body Weight; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Drug Resistance; Female; Hemorrhage; Humans; Male; Middle Aged; Obesity; Odds Ratio; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 25897998
DOI: 10.1016/j.atherosclerosis.2015.04.015 -
Journal of Thrombosis and Thrombolysis Aug 2023Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a... (Meta-Analysis)
Meta-Analysis Review
Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 10/µl and the median nadir platelet count was 52 (31-90.5) x 10/µl.
Topics: Humans; Heparin; Heparinoids; COVID-19; Thrombocytopenia; Anticoagulants; Thrombosis
PubMed: 37219826
DOI: 10.1007/s11239-023-02827-5 -
Seminars in Thrombosis and Hemostasis Jul 2023Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet...
Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet function during the storage period, their effect on platelet storage lesions, and the optimal storage duration following PRTs have not been clearly defined. The aim of this study was to systematically review the existing literature and investigate the impact of PRTs on functional alterations of PRT-treated platelets during the storage period. The authors identified 68 studies suitable to be included in this review. Despite the high heterogeneity in the literature, the results of the published studies indicate that PRTs may increase platelet metabolic activity, accelerate cell apoptosis, and enhance platelet activation, which can subsequently lead to a late exhaustion of activation potential and reduced aggregation response. However, these effects have a minor impact on platelet function during the early storage period and become more prominent beyond the fifth day of the storage period. Large in vivo trials are required to evaluate the effectiveness of PRT-treated platelets during the storage period and investigate whether their storage can be safely extended to more than 5 days, and up to the traditional 7-day storage period.
Topics: Humans; Blood Platelets; Platelet Activation; Blood Preservation; Platelet Transfusion
PubMed: 36252605
DOI: 10.1055/s-0042-1757897 -
Heliyon Feb 2024Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated...
BACKGROUND
Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications.
METHODS
In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464).
RESULTS
Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels.
CONCLUSION
These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.
PubMed: 38356516
DOI: 10.1016/j.heliyon.2024.e25537 -
Platelets 2020Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its... (Meta-Analysis)
Meta-Analysis
Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its influence on platelet ADP-P2Y12 receptor inhibitors lack consistency. Thus, we conducted a systematic review and meta-analysis of already existing data/studies to further explore this issue. PubMed, Web of science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception to March 2018. Studies investigating the residual platelet reactivity categorized by smoking status and patients treated with platelet ADP-P2Y12 receptor inhibitors qualified the inclusion criteria. The primary outcome was P2Y12 reaction unit (PRU) value measured by VerifyNow P2Y12 assay, compared with different smoking status in ADP-P2Y12 receptor inhibitors treatment groups. Secondary outcome was post-treatment with 5 μmol/L ADP-inhibition of platelet aggregation (ADP-IPA) measured by light transmittance aggregometry (LTA). Of the 4954 citations retrieved, 12 studies involving 16 296 patients with acute coronary syndrome and/or stent deployment using platelet ADP-P2Y12 receptor inhibitors were included for meta-analysis. Pooled analysis revealed that PRU values of current smokers were 25.70 lower than nonsmokers (95% CI -38.81 to -12.60, = 0.0001), getting better effects of antiplatelet treatment. In the smoking extent subgroup analysis, patients smoking >10 cigarettes/day shown about 46.49 lower of PRU values than patients smoking <10 cigarettes/day ( < 0.00001). Racial subgroup analyses found that smokers had increased platelet inhibition in the Caucasian population. Further, pooled analysis of ADP-IPA values for 1658 patients from five studies showed a significantly lower residual platelet reactivity in current smokers compared to that in nonsmokers (MD = -4.19; 95% CI -6.55 to -1.83; = 0.0005). This systematic review and meta-analysis suggested that smokers have increased platelet inhibition and lower aggregation in response to clopidogrel than nonsmokers. These residual platelet reactivity observations may help to explain differential clinical outcomes in smokers vs. nonsmokers in large scale clinical trials.
Topics: Adult; Aged; Biomarkers; Blood Platelets; Clopidogrel; Humans; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Publication Bias; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Smoking
PubMed: 30744477
DOI: 10.1080/09537104.2019.1572878 -
Autoimmunity Reviews May 2021Patients with systemic lupus erythematosus (SLE) have a high burden of cardiovascular disease (CVD) of multifactorial origin. The aim of this systematic review is to... (Review)
Review
OBJECTIVE
Patients with systemic lupus erythematosus (SLE) have a high burden of cardiovascular disease (CVD) of multifactorial origin. The aim of this systematic review is to analyze the role of the interferon I (IFN-I) signature and fibroblast growth factor-23 (FGF-23) in patients with SLE or cutaneous lupus erythematosus (CLE) herein.
MATERIALS AND METHODS
We conducted a systematic literature search in PubMed and Scopus using keywords for major adverse cardiovascular events (MACE) and intermediate outcomes (endothelial dysfunction, subclinical atherosclerosis, platelet activation) associated with IFN-I or FGF-23 in patients with SLE and CLE.
RESULTS
4745 citations were screened, of which 12 studies were included. IFN-I was associated with MACE in two third of the studies and the association was strongest for cardiac events. An association of IFN-I was found in all studies investigating impaired vascular function, but only in 50% (respectively 40%) of reports examining the relation of IFN-I and platelet activation (respectively subclinical atherosclerosis). Altogether the reports were of variable bias and quality due to high variability of examined IFN-I biomarkers and inconsistent results for different outcome measures. No studies investigating the cardiovascular risk of circulating IFN-I in CLE, nor FGF-23 in SLE or CLE were found.
CONCLUSION
Clinical studies measuring the association between IFN-I and direct / intermediate measures of CVD are rare and ambiguous in SLE and nonexistent in CLE, hampering a definite conclusion.
Topics: Cardiovascular Diseases; Fibroblast Growth Factor-23; Heart Disease Risk Factors; Humans; Interferon Type I; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Risk Factors
PubMed: 33722754
DOI: 10.1016/j.autrev.2021.102794 -
International Journal of Molecular... Jul 2021In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of...
In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Endothelial Cells; Humans; Leukocytes; P-Selectin
PubMed: 34360707
DOI: 10.3390/ijms22157942 -
Chinese Journal of Integrative Medicine Nov 2021To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD).
METHODS
The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.
RESULTS
The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups.
CONCLUSIONS
Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS.
Topics: Blood Coagulation; Blood Platelets; Coronary Disease; Humans; Platelet Aggregation; Tissue Plasminogen Activator
PubMed: 34532747
DOI: 10.1007/s11655-021-2871-2 -
Pregnancy Hypertension Jul 2018Mean platelet volume (MPV) has been explored in several observational studies in the field of preeclampsia and current evidence seem to be conflicting. The purpose of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Mean platelet volume (MPV) has been explored in several observational studies in the field of preeclampsia and current evidence seem to be conflicting. The purpose of the present meta-analysis is to evaluate the reported MPV differences in patients that develop preeclampsia and to compare them to those of otherwise healthy women.
DESIGN AND METHODS
We searched the international literature using the Medline (1966-2018), Scopus (2004-2018), EMBASE (1947-2018) and Clinicaltrials.gov (2008-2018) databases. Statistical meta-analysis was performed using the RevMan 5.3 software.
RESULTS
The meta-analysis was based on outcomes reported from 50 studies that included 14,614 women. MPV was significantly higher in preeclamptic than healthy pregnant women (7905 women, MD: 1.04 fl, 95% CI [0.76, 1.32]). The mean difference was less evident among women with mild preeclampsia (6604 women, MD: 0.65 fl, 95% CI [0.19, 1.11]), compared to the severe ones (6119 women, MD: 1.28 fl, 95% CI [0.75, 1.80]). The results of the univariate meta-regression analysis showed that region, sample size, time to analysis, anticoagulant, platelet count and NOS score did not affect the outcomes of the meta-analysis.
CONCLUSIONS
The findings of our meta-analysis suggest that mean platelet volume represents a promising biomarker for the detection and follow-up of patients that develop preeclampsia. However, given that the available evidence is drawn from case-control studies, future cohorts are needed in this field to accurately determine optimal timing and cut-off values that may be used in the clinical setting.
Topics: Blood Platelets; Blood Pressure; Female; Humans; Mean Platelet Volume; Platelet Activation; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Prognosis; Risk Factors
PubMed: 30177049
DOI: 10.1016/j.preghy.2018.06.016 -
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