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Molekuliarnaia Biologiia 2018The heritable component of susceptibility to myocardial infraction (MI) remains unexplained, possibly due to the minor effects of genes, which are not obviously...
The heritable component of susceptibility to myocardial infraction (MI) remains unexplained, possibly due to the minor effects of genes, which are not obviously associated with the disease. These genes may be integrated in miRNA regulated networks associated with myocardial infarction. A systematic review of the literature led us to selecting rs2910164 (MIR146A), rs11614913 (MIR196A2), and rs3746444 (MIR499А) variants to study the association with the MI phenotype. In ethnic Russians, variant rs11614913*C (MIR196A2) was found to be associated with the risk of myocardial infraction (p = 0.023, OR = 1.74) for the first time; this association was validated in an independent cohort. The gene-gene interaction network for experimentally validated miR-196a2 target genes was built and analyzed. One of its four topological clusters contained the majority of miR-196a2 target genes associated with atherosclerosis, coronary artery disease or myocardial infarction and was enriched with the genes regulating the TGFβ and class I MHC signaling pathways, platelet activation/aggregation, and the cell cycle control. This analysis points towards the role of miR-196a2 in the pathological coronary phenotypes and opens up an avenue for further investigations.
Topics: Genetic Predisposition to Disease; Humans; MicroRNAs; Myocardial Infarction; Phenotype; Polymorphism, Single Nucleotide; Signal Transduction
PubMed: 30633243
DOI: 10.1134/S0026898418060149 -
Hepatology International Jan 2019While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.
METHODS
We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.
RESULTS
Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p ≤ 0.0001). The statistical heterogeneity among the studies was insignificant.
CONCLUSION
Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.
Topics: Adult; Aged; Chronic Disease; End Stage Liver Disease; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Treatment Outcome
PubMed: 30539518
DOI: 10.1007/s12072-018-9918-2 -
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 -
Research and Practice in Thrombosis and... Oct 2018Fondaparinux is commonly used for treatment of heparin-induced thrombocytopenia (HIT) despite lack of approval for this indication. High quality randomized controlled...
BACKGROUND
Fondaparinux is commonly used for treatment of heparin-induced thrombocytopenia (HIT) despite lack of approval for this indication. High quality randomized controlled trials of this agent are unlikely to be forthcoming.
OBJECTIVES
The objective of this systematic review is to update the literature on the efficacy and safety of fondaparinux for treatment of confirmed and probable HIT based on the available evidence.
METHODS
Primary articles were identified using Web of Science and PubMed database searches for English-language studies from January 2006 to November 2017. Selected studies enrolled consecutive adult patients who received fondaparinux as the primary anticoagulant to treat acute HIT; confirmed the diagnosis by serological testing with a serotonin-release assay; heparin-induced platelet activation assay or enzyme-linked immunosorbent assay; provided clinical criteria used to define HIT and reported clinically important outcomes.
RESULTS
A total of 9 studies were identified with 154 HIT positive patients. Ten experienced a new thrombotic event while receiving fondaparinux (6.5%, 95% CI, 3.4 to 11.7%) and 26 experienced major bleeding (16.9%, 95% CI, 11.7 to 23.6%). Mortality due to thrombosis or bleeding was reported in 5 patients (3.2%, 95% CI, 1.2 to 7.6%).
CONCLUSIONS
Fondaparinux appears to be an effective and safe anticoagulant for treatment of acute HIT despite the absence of randomized trials. Caution should exercised when using fondaparinux in patients with renal insufficiency.
PubMed: 30349886
DOI: 10.1002/rth2.12145 -
Critical Care (London, England) Aug 2018Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage,...
BACKGROUND
Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain.
METHODS
We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries.
RESULTS
Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n = 4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs.
CONCLUSIONS
PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.
Topics: Blood Platelets; Critical Illness; Drug Storage; Humans; Platelet Transfusion; Treatment Outcome
PubMed: 30077181
DOI: 10.1186/s13054-018-2114-x -
Journal of Pharmacy & Pharmaceutical... 2018Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is... (Meta-Analysis)
Meta-Analysis
PURPOSE
Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed.
METHODS
We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib.
RESULTS
In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict.
CONCLUSION
Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiovascular Diseases; Humans; Platelet Aggregation; Treatment Outcome
PubMed: 29891025
DOI: 10.18433/jpps29854 -
Plastic and Reconstructive Surgery.... Dec 2017The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent...
BACKGROUND
The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies.
METHODS
In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data.
RESULTS
From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios.
CONCLUSIONS
Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice.
PubMed: 29632775
DOI: 10.1097/GOX.0000000000001596 -
PloS One 2017Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. (Review)
Review
INTRODUCTION
Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined.
AIM
The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia.
METHODS
A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia.
RESULTS
The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR.
CONCLUSION
Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.
Topics: Antipsychotic Agents; Computational Biology; Genetic Predisposition to Disease; Humans; Pneumonia
PubMed: 29077727
DOI: 10.1371/journal.pone.0187034 -
The Cochrane Database of Systematic... Apr 2017Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012.
OBJECTIVES
The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH).
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use the accepted definition of HIT. This was defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained greater than 150 x 10/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, we required circulating antibodies associated with the syndrome to have been investigated through laboratory assays.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author.
MAIN RESULTS
In this update, we included three trials involving 1398 postoperative participants. Participants were submitted to general surgical procedures, minor and major, and the minimum mean age was 49 years. Pooled analysis showed a significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was consistently reduced comparing participants undergoing major surgical procedures exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The occurrence of HIT complicated by venous thromboembolism was significantly lower in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84); low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one participant who received UFH. There were no amputations or deaths documented. Although limited evidence is available, it appears that HIT induced by both types of heparins is common in people undergoing major surgical procedures (incidence greater than 1% and less than 10%).
AUTHORS' CONCLUSIONS
This updated review demonstrated low-quality evidence of a lower incidence of HIT, and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in people undergoing major surgical procedures was lower when treated with LMWH compared to UFH (low-quality evidence). The quality of the evidence was downgraded due to concerns about the risk of bias in the included studies and imprecision of the study results. These findings may support current clinical use of LMWH over UFH as front-line heparin therapy. However, our conclusions are limited and there was an unexpected paucity of RCTs including HIT as an outcome. To address the scarcity of clinically-relevant information on HIT, HIT must be included as a core harmful outcome in future RCTs of heparin.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Numbers Needed To Treat; Postoperative Complications; Randomized Controlled Trials as Topic; Surgical Procedures, Operative; Thrombocytopenia; Thrombosis; Venous Thrombosis
PubMed: 28431186
DOI: 10.1002/14651858.CD007557.pub3 -
Medical Science Monitor Basic Research Mar 2017BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS Literature search of all major databases retrieved 1,676 studies. After screening, a total of 73 studies were identified. Pooled analysis showed significant differences in PC (weighted mean difference (WMD)=-26.93 and p<0.001), MPV (WMD=0.61 and p<0.001), PDW (WMD=-0.22 and p=0.002), BTG (WMD=24.69 and p<0.001), PF4 (WMD=4.59 and p<0.001), and p-selectin (WMD=4.90 and p<0.001). CONCLUSIONS Platelets play a critical and precipitating role in the occurrence of AF. Whereas distribution width of platelets as well as factors of platelet activity was significantly greater in AF patients compared to SR patients, platelet count was significantly lower in AF patients.
Topics: Atrial Fibrillation; Blood Coagulation; Blood Platelets; Humans; Platelet Activation; Platelet Count; Stroke
PubMed: 28302997
DOI: 10.12659/msmbr.902557