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Journal of Stroke and Cerebrovascular... Jul 2020To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients.
METHODS
We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included.
RESULTS
Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I = 0.01%, p = 0.475).
CONCLUSIONS
This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance.
Topics: Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Resistance; Humans; Ischemic Attack, Transient; Pharmacogenomic Variants; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Risk Factors; Stroke; Treatment Outcome
PubMed: 32414579
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104877 -
Thrombosis and Haemostasis Jun 2020The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number...
The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.
Topics: Algorithms; Betacoronavirus; COVID-19; Cardiology; Coronavirus Infections; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Liver Failure; Pandemics; Partial Thromboplastin Time; Platelet Count; Pneumonia, Viral; Prothrombin Time; Risk; SARS-CoV-2; Thrombophilia; Thrombosis; Treatment Outcome
PubMed: 32349133
DOI: 10.1055/s-0040-1710317 -
Intensive Care Medicine Jun 2020Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings... (Meta-Analysis)
Meta-Analysis Review
Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9-29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6-61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8-34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8-5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.
Topics: Adult; Blood Platelets; Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Platelet Count; Thrombocytopenia
PubMed: 32328725
DOI: 10.1007/s00134-020-06031-4 -
Journal of Cardiovascular Pharmacology... May 2020Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450...
Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review.
BACKGROUND AND OBJECTIVES
Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS.
METHODS
A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment.
RESULTS
The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality.
CONCLUSION
Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI.
Topics: Acute Coronary Syndrome; Clinical Decision-Making; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Costs; Humans; Patient Selection; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Predictive Value of Tests; Ticagrelor; Treatment Outcome
PubMed: 32027168
DOI: 10.1177/1074248420902298 -
Journal of Ethnopharmacology Apr 2020Endothelial dysfunction is involved in lesion generation by the promotion of both early and late mechanism(s) of atherosclerosis such as adhesion molecules...
ETHNOPHARMACOLOGICAL RELEVANCE
Endothelial dysfunction is involved in lesion generation by the promotion of both early and late mechanism(s) of atherosclerosis such as adhesion molecules up-regulation, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, cytokine elaboration, platelet activation and vascular smooth muscle cell migration, and proliferation. Nigella sativa is from the Ranunculaceae family which is used in some countries for various medicinal purposes. Nigella sativa seed has been widely used in traditional medicine for the treatment of diabetes.
AIM OF THE REVIEW
This review article summarized the therapeutic effects of Nigella sativa on endothelial dysfunction.
METHODS
Databases such as PubMed, Web of Science, Google Scholar, Scopus, and Iran Medex were considered. The search terms were " Nigella sativa " or "endothelium" and " Diabetes"," endothelial dysfunction ", " Thymoquinone " and " anti-inflammatory effect ".
RESULTS
The current review shows that Nigella sativa and Thymoquinone have a protective effect on endothelial dysfunction induced by diabetes. This is done by several mechanisms such as reduction of inflammatory and apoptotic markers, improving hyperglycemia, hyperlipidemia and antioxidant function, inhibiting platelet aggregation, and regulating eNOS, VCAM-1 and LOX-1 genes expression that involve in the endothelial dysfunction. Thymoquinone also reduces expression and secretion of some cytokines such as MCP-1, interleukin-1β, TNF-α, NF-κB, and Cox-2 that result in anti-inflammation effect.
CONCLUSION
Thymoquinone, the main phenolic terpene found in Nigella sativa, has several important properties such as antidiabetic, anti-inflammatory, and antioxidant activity. Therefore, Nigella sativa can improve endothelial dysfunction.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Diabetes Mellitus; Endothelium, Vascular; Humans; Hypoglycemic Agents; Nigella sativa; Plant Extracts; Vascular Diseases
PubMed: 31972323
DOI: 10.1016/j.jep.2020.112585 -
Clinical Oral Investigations Feb 2020To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior.
OBJECTIVE
To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior.
METHODS
A systematic electronic search using MEDLINE database was performed. In vitro studies using PRF were considered and articles published up to June 31, 2018 were screened. Eligible studies were selected based on the use of human PRF.
RESULTS
In total, 1746 titles were identified with the search terms, from these 37 met the inclusion criteria and were chosen for data extraction. In addition, 16 new studies, mainly published in 2019, were also included in the analysis resulting in 53 studies. No meta-analysis could be performed due to the heterogeneity of study designs. Included studies show that PRF enhances proliferation, migration, adhesion, and osteogenic differentiation on a variety of cell types along with cell signaling activation. Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells. Despite some notable differences of the studies, the overall findings suggest a positive effect of PRF on cell proliferation, migration, adhesion, differentiation, and inflammation pointing towards a therapeutic potential in regenerative dentistry.
CLINICAL RELEVANCE
PRF serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. Although the cellular mechanisms by which PRF supports the clinical outcomes remain unclear, in vitro research provides possible explanations. This systematic review aims to provide an update of the existing research on how PRF affects basic physiological processes in vitro. The overall findings suggest that PRF induces cell proliferation, migration, adhesion, and differentiation along with possessing anti-inflammatory properties further supporting its therapeutic potential in wound healing and bone regeneration.
Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Humans; Inflammation; Osteogenesis; Platelet-Rich Fibrin
PubMed: 31879804
DOI: 10.1007/s00784-019-03156-9 -
Frontiers in Cardiovascular Medicine 2019Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality...
Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality associated with bleeding and clotting complications remain high in pediatric patients undergoing ECMO. Platelets, a key element of the coagulation system, have been proposed to be the main cause of coagulopathy in the setting of ECMO. This systematic review aims to summarize and discuss the existing knowledge of platelet phenotype and function in the pediatric ECMO population. A systematic review was conducted for the Embase, Medline, and PubMed databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The detailed study selection process yielded a total of 765 studies and only 3 studies that fulfilled the selection criteria were included in this review. Techniques used to assess platelet function in the three existing studies included platelet aggregometry, flow cytometry, and thromboelastography-platelet mapping. The finding that is common to the three studies is reduced platelet function in pediatric patients during ECMO either compared to before the initiation of ECMO or in non-survivors compared to survivors. Two studies demonstrated reduced platelet aggregation that are irreversible by platelet transfusion during ECMO. Two studies reported bleeding events and mortality in children on ECMO and none of the studies investigated thrombotic events. This systematic review demonstrates the extremely limited information available for platelet phenotype and function in the pediatric ECMO population. Evidence from the existing literature suggests reduced platelet aggregation and increased platelet activation in children during ECMO. However, this needs to be interpreted with care due to the limitations associated with the techniques used for platelet function testing. Furthermore, the association between platelet dysfunction and clinical outcomes in the pediatric ECMO population remains elusive. Multiple research gaps have been identified when it comes to the knowledge of platelet phenotype and function of children on ECMO, highlighting the need for robust, well-designed studies in this setting.
PubMed: 31620448
DOI: 10.3389/fcvm.2019.00137 -
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 -
The World Journal of Biological... Jun 2020Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This... (Meta-Analysis)
Meta-Analysis
Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR, MLR and PLR in non-affective psychosis. Eight studies have been identified from the main electronic databases. Meta-analyses based on random-effects models have been carried out generating pooled standardised mean differences (SMDs) between non-affective psychotic patients and healthy controls (HCs). Subjects with non-affective psychosis had a significant higher NLR and MLR as compared with HC (respectively SMD = 0.715; < 0.001; =57.565% and SMD = 0.417; = 0.001; =65.754%), confirmed by heterogeneity-based sensitivity analysis. Subgroup analyses showed no differences in effect size across different study characteristics, including drug treatment status, diagnosis, and setting. Meta-regression showed that age influenced the relationship between non-affective psychosis and MLR. A trend of significance, not confirmed by heterogeneity-based sensitivity analysis, was observed in PLR with patients showing higher PLR than HC. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in non-affective psychosis and inflammatory ratios, especially NLR and MLR, may be useful to detect this activation.
Topics: Blood Platelets; Humans; Lymphocytes; Monocytes; Neutrophils; Psychotic Disorders
PubMed: 30806142
DOI: 10.1080/15622975.2019.1583371 -
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