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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 -
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 -
Clinical Toxicology (Philadelphia, Pa.) Oct 2019Cannabis smoking can result in elevation of heart rate and blood pressure immediately after use, possibly from sympathetic nervous system stimulation and...
Cannabis smoking can result in elevation of heart rate and blood pressure immediately after use, possibly from sympathetic nervous system stimulation and parasympathetic nervous system inhibition. Vascular inflammation, platelet activation, and carboxyhemoglobin generation have also been proposed as potential side effects of cannabis smoking. As such, an association between cannabis use and acute coronary syndrome has been postulated. The objective of our study was to analyze systematically the medical literature pertaining to this putative association. PubMed, Google Scholar, and OpenGrey were queried using a unique search string. All human trials, case series, or case reports of cannabis use and acute coronary syndrome in any language were considered in the literature search. The definition of acute coronary syndrome represented a penumbra that included chest pain, angina pectoris, unstable angina, myocardial infarction, myocardial ischemia, and cardiac arrest. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Our final search strategy included free-text words (TW): ("cannabis"[TW] OR "marijuana"[TW]) AND ("acute coronary syndrome"[TW] OR "myocardial" OR "ischemia"[TW] OR "infarction"[TW] OR "chest pain"[TW] OR "cardiac arrest"[TW] OR "angina"[TW]). To remain consistent over a span of five decades, we specifically did not include any publications with non-phytogenic, non-smoked cannabis as the sole etiology, as these are relatively recent and may possess additional pharmacologic characteristics compared to phytogenic cannabinoids. Therefore, for the purpose of this review, the term "cannabis" refers to the smoked phytogenic form. The search resulted in 325 articles. References in each selected publication were carefully hand-searched for any additional reports having relevance, and a total of 12 publications were identified in this manner. Following comparison and discussion amongst the co-authors, duplicate and non-relevant publications were removed, and a total of 85 publications involving 541,518 human subjects were selected for inclusion. Results were synthesized and reviewed by the authors for relevance. Clinical trials, observational studies, retrospective studies, case series, and case reports were graded using Oxford Centre for Evidence-based Medicine guidelines. There were no Level I randomized blinded controlled studies specifically addressing the cannabis/acute coronary syndrome association. However, there were five Level I systematic reviews, 14 Level II studies with 83,961 subjects, and 14 Level III studies with 457,495 subjects. Conclusions from 28 of these 33 studies highlighted an increased risk of both acute coronary syndrome and chronic cardiovascular disease from cannabis use. The systematic reviews were wide-ranging in topic and scale, and none specifically focused on the association between cannabis use and acute coronary syndrome. The dissenting studies included two systematic reviews, one concluding there was limited and weak evidence for association of cardiovascular disease and acute coronary syndromes with cannabis use, and another citing the evidence was inconclusive. The other dissenting articles were two longitudinal prospective studies and a retrospective review concluding cannabis users had lower post-myocardial infarction mortality. There were 51 case series (Level IV) and case reports (Level V) with 62 subjects. Six cases were female (10%). Average age was 31 ± 12 years, reported maximum heart rate was 88 ± 21 bpm, systolic blood pressure was 125 ± 32 mmHg, and diastolic blood pressure was 80 ± 17 mmHg. ST-segment elevation was documented on 37 (60%) electrocardiograms, and the most common angiographic finding was left anterior descending coronary arterial occlusion and/or stenosis in 22 (35%) patients. Concomitant cardiomyopathy was described in 21 (34%) cases. There were 14 (23%) deaths attributed to acute coronary syndrome associated with cannabis use. There were five Level I systematic reviews, 14 Level II studies with 83,961 subjects, and 14 Level III studies with 457,495 subjects. All but five Level I-III publications highlighted an increased risk of both acute coronary syndrome and chronic cardiovascular disease associated with cannabis use.
Topics: Acute Coronary Syndrome; Adolescent; Adult; Aged; Aged, 80 and over; Cannabis; Female; Humans; Male; Marijuana Smoking; Middle Aged; Prospective Studies; Retrospective Studies; Risk Assessment; Young Adult
PubMed: 30964363
DOI: 10.1080/15563650.2019.1601735 -
Lipids in Health and Disease May 2019Combination of statins and clopidogrel is frequently administered in patients with coronary artery disease (CAD). They are mainly activated and eliminated in the liver... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combination of statins and clopidogrel is frequently administered in patients with coronary artery disease (CAD). They are mainly activated and eliminated in the liver by cytochrome P450 isoenzyme 3A4 (CYP3A4). The aim was to clarify whether the coadministration of clopidogrel and statins attenuate respective efficacy.
METHODS
PubMed, Embase, the Cochrane Library, Web of Science and Clinical Trials. gov were searched for until August 2018. Randomized controlled trials (RCTs) and cohort studies were taken into quality evaluation. Data were pooled using random effect models to estimate standard mean difference (SMD) or risk ratio (RR) with 95% confidence interval (CI).
RESULTS
In total, 28 studies representing 25,267 participants were included. Statins reduce the mortality of patients administered clopidogrel (RR 0.54; 95% CI 0.40,0.74; p = 0.000), no differences were found in platelet aggregation (PA) (SMD 0.02; 95% CI -0.38,0.42; p = 0.920) and the expressions of P-selectin (SMD -0.04; 95% CI -0.14,0.05; p = 0.346), CD40L (SMD 0.09; 95% CI -0.29,0.48; p = 0.633), CD63 (SMD 0.09; 95% CI -0.01,0.19; p = 0.079) and PAC-1 (SMD 0.03; 95% CI -0.08,0.13; p = 0.633). Furthermore, CYP3A4 metabolized or non-CYP3A4 metabolized statins have no discrepancies in PA (SMD 0.13; 95% CI -0.31,0.58; p = 0.556), P-selectin (SMD 0.17; 95% CI -0.16,0.51; p = 0310), death (RR 0.89; 95% CI 0.38,2.07; p = 0.791), except for triglyceride (TG) (SMD -0.19; 95% CI -0.33,-0.06; p = 0.005).
CONCLUSIONS
This meta-analysis confirmed that statins reduce mortality in patients undergoing clopidogrel treatment without affecting platelet activation and aggregation.
Topics: Clopidogrel; Cytochrome P-450 CYP3A; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Mortality; Platelet Aggregation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31122249
DOI: 10.1186/s12944-019-1053-0 -
Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients: A Systematic Review.Frontiers in Cardiovascular Medicine 2018Hemorrhagic and thromboembolic complications are common during treatment with extracorporeal membrane oxygenation (ECMO), resulting in considerable morbidity and...
Hemorrhagic and thromboembolic complications are common during treatment with extracorporeal membrane oxygenation (ECMO), resulting in considerable morbidity and mortality. This emphasizes the clinical relevance of understanding hemostatic changes occurring during ECMO treatment. As platelets are key players in hemostasis, detailed knowledge on how ECMO treatment affects platelet function is of great importance. We therefore aimed to systematically summarize and discuss existing knowledge on platelet function during ECMO treatment in adult patients. Systematic review complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Objectives and methods were specified in a PROSPERO protocol (ID no CRD42018084059). The MEDLINE/PubMed, EMBASE, and Web of Science databases were systematically searched on September 10, 2018. A standardized quality assessment tool was used to assess the risk of bias in included studies. Primary outcome was platelet function during ECMO treatment, measured as platelet adhesion, activation or aggregation. Secondary outcomes were thrombosis, bleeding, and mortality during ECMO treatment. A total of 591 studies were identified, of which seven were eligible for inclusion in the qualitative synthesis. Of these, one study investigated expression of platelet adhesion receptors and found them to be reduced during ECMO treatment; two studies reported a decrease in platelet activation markers during ECMO treatment; and five studies demonstrated reduced platelet aggregation during ECMO treatment. Three studies reported on thrombosis, mortality and/or bleeding during ECMO treatment; no thromboembolic events were reported; all three studies reported frequent bleeding episodes defined on basis of transfusion requirements. An in-hospital mortality of 35-40% and a 30-day mortality of roughly 30% were reported in three different studies. The present systematic review reveals a substantial knowledge gap regarding platelet function during ECMO treatment in adult patients and underscores the demand for more and well-designed studies on this topic. There is suggested evidence of reduced platelet adhesion, decreased platelet activation, and reduced platelet aggregation in adult patients during ECMO treatment. Importantly, platelet aggregation results need to be interpreted in the light of low platelet counts. The associations of platelet function and bleeding and/or thromboembolic complications during ECMO treatment remain to be fully elucidated.
PubMed: 30474031
DOI: 10.3389/fcvm.2018.00157 -
Aesthetic Surgery Journal Mar 2017Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide... (Review)
Review
BACKGROUND
Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide popularity in aesthetic surgery as a result of uncertainty surrounding objective clinical evidence.
OBJECTIVES
We aim to describe the current applications, define preparation and activation, explore effectiveness, and propose a classification system to facilitate comparisons across studies.
METHODS
A comprehensive review of the literature regarding the use of platelet rich plasma in aesthetic surgery was performed. Data gathered included: PRP application, study type, subject number, centrifugation, anticoagulation, activation, PRP composition, and outcomes.
RESULTS
Thirty-eight reports were identified. Applications included injection into aging skin (29%), scalp alopecia (26%), lipofilling (21%), fractional laser (13%), and facial surgery (11%). The majority of studies (53%) were case series without controls. Leucocytes were sparsely defined (32%). The concentration of injected and/or baseline platelets was rarely clarified (18%). The mechanism of activation was described in 27 studies (71%), while anticoagulation was uncommonly elucidated (47%). While most studies (95%) claim effectiveness, objective measures were only utilized in 17 studies (47%).
CONCLUSIONS
Current studies produce context-dependent results with a lack of consistent reporting of PRP preparation, composition, and activation in aesthetic applications, making meaningful meta-analysis unrealistic. Thus the method of PRP preparation warrants increased attention. We recommend a set of descriptors, FIT PAAW (described below), to produce scientifically grounded conclusions, facilitating a clearer understanding of the situations in which PRP is effective.
LEVEL OF EVIDENCE
4
Topics: Cosmetic Techniques; Esthetics; Humans; Platelet-Rich Plasma; Plastic Surgery Procedures; Treatment Outcome
PubMed: 28207031
DOI: 10.1093/asj/sjw178 -
Phytotherapy Research : PTR Nov 2022The increment of platelet aggregation factors has been considered a key phenomenon in atherosclerosis. Studies have shown that garlic (Allium sativum) is associated with... (Review)
Review
The increment of platelet aggregation factors has been considered a key phenomenon in atherosclerosis. Studies have shown that garlic (Allium sativum) is associated with a reduction in platelet aggregation and thrombosis. Hence, the present systematic review was conducted to evaluate the effect of garlic on platelet aggregation. All randomized controlled trials (RCTs) with keywords related to garlic and platelet aggregation were thoroughly searched in electronic databases including PubMed, Scopus, ISI Web of Science, and Google Scholar up to January 2021. Moreover, the references of all related articles were screened to discover more relevant studies. The quality of each study was reported based on Cochrane Collaboration's tool. In total, 12 studies met the inclusion criteria from 18,235 identified articles (including 595 participants). Most of the studies assessed platelet aggregation in response to different inducers. Of the 12 clinical trials, six studies depicted the beneficial effect of garlic on reducing platelet aggregation. The summary of the quality assessment indicated that most of the studies had high-quality scores. Regarding the small number of RCTs and heterogeneity between studies, it is impossible to make a proper conclusion about the impacts of garlic on platelet aggregation. Therefore, further precise trials with a standard design are necessary to validate the anti-thrombotic effect of garlic.
Topics: Humans; Garlic; Platelet Aggregation; Randomized Controlled Trials as Topic; Antioxidants; Biological Products; Dietary Supplements
PubMed: 36222178
DOI: 10.1002/ptr.7556 -
Frontiers in Cardiovascular Medicine 2022Humans have been ascending to high altitudes for centuries, with a growing number of professional- and leisure-related sojourns occurring in this millennium. A multitude...
Humans have been ascending to high altitudes for centuries, with a growing number of professional- and leisure-related sojourns occurring in this millennium. A multitude of scientific reports on hemostatic disorders at high altitude suggest that hypoxia is an independent risk factor. However, no systematic analysis of the influence of environmental hypoxia on coagulation, fibrinolysis and platelet function has been performed. To fill this gap, we performed a systematic literature review, including only the data of healthy persons obtained during altitude exposure (<60 days). The results were stratified by the degree of hypoxia and sub-categorized into active and passive ascents and sojourns. Twenty-one studies including 501 participants were included in the final analysis. Since only one study provided relevant data, no conclusions regarding moderate altitudes (1,500-2,500 m) could be drawn. At high altitude (2,500-5,400 m), only small pathophysiological changes were seen, with a possible impact of increasing exercise loads. Elevated thrombin generation seems to be balanced by decreased platelet activation. Viscoelastic methods do not support increased thrombogenicity, with fibrinolysis being unaffected by high altitude. At extreme altitude (5,400-8,850 m), the limited data showed activation of coagulation in parallel with stimulation of fibrinolysis. Furthermore, multiple confounding variables at altitude, like training status, exercise load, fluid status and mental stress, prevent definitive conclusions being drawn on the impact of hypoxia on hemostasis. Thus, we cannot support the hypothesis that hypoxia triggers hypercoagulability and increases the risk of thromboembolic disorders, at least in healthy sojourners.
PubMed: 35252392
DOI: 10.3389/fcvm.2022.813550 -
American Heart Journal Jun 2017VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error.
METHODS
Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta-analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method.
RESULTS
The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r=-0.349; P<.001; 10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r=-0.526; P<.001; 8 studies with 4,395 patients). % Inhibition (r=0.081; P=.059; 6 studies with 3,832 patients) and ΔPRU (r=-0.037; P=.188; 5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta-analysis (3,533 patients pooled from 5 studies; r=-0.335; P<.001). Light transmission aggregometry (r=0.160; P=.072; 4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r=-0.029; P=.394; 3 studies with 7,645 patients) showed no significant association with hemoglobin.
CONCLUSIONS
A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.
Topics: Blood Platelets; Coronary Artery Disease; Hemoglobins; Humans; Platelet Aggregation; Platelet Function Tests; Purinergic P2Y Receptor Antagonists
PubMed: 28577681
DOI: 10.1016/j.ahj.2017.03.006 -
Shock (Augusta, Ga.) Jan 2017The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury.
METHODS
We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. Medline, embase, and cochrane databases were searched.
RESULTS
The literature search yielded 1,314 unique articles. Fifteen preclinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g., ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps, and prostaglandins. High-dose ASA may be the drug of choice. A meta-analysis of three clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36-0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality.
CONCLUSION
This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models are being evaluated to guide optimal timing and dose, before prospective randomized trials.
Topics: Animals; Aspirin; Humans; Platelet Activation; Respiratory Distress Syndrome
PubMed: 27984533
DOI: 10.1097/SHK.0000000000000745