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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 -
British Journal of Clinical Pharmacology Aug 2008The aim was to perform a systematic review of all candidate gene association studies in aspirin resistance. (Review)
Review
AIMS
The aim was to perform a systematic review of all candidate gene association studies in aspirin resistance.
METHODS
Electronic databases were searched up until 1 December 2007 for all studies investigating any candidate gene for aspirin resistance in humans. Aspirin resistance was required to have been measured by a standardized laboratory technique to be included in the analysis.
RESULTS
Within 31 studies, 50 polymorphisms in 11 genes were investigated in 2834 subjects. The PlA1/A2 polymorphism in the GPIIIa platelet receptor was the most frequently investigated, with 19 studies in 1389 subjects. The PlA1/A2 variant was significantly associated with aspirin resistance when measured in healthy subjects [odds ratio (OR) 2.36, 95% confidence interval (CI) 1.24, 4.49; P = 0.009]. Combining genetic data from all studies (comprising both healthy subjects and those with cardiovascular disease) reduced the observed effect size (OR 1.14, 95% CI 0.84, 1.54; P = 0.40). Moreover, the observed effect of PlA1/A2 genotype varied depending on the methodology used for determining aspirin sensitivity/resistance. No significant association was found with aspirin resistance in four other investigated polymorphisms in the COX-1, GPla, P2Y1 or P2Y12 genes.
CONCLUSIONS
Our data support a genetic association between the PlA1/A2 molecular variant and aspirin resistance in healthy subjects, with the effect diminishing in the presence of cardiovascular disease. The laboratory methodology used influences the detection of aspirin resistance. However, as heterogeneity was significant and our results are based on a limited number of studies, further studies are required to confirm our findings.
Topics: Aspirin; Cardiovascular Diseases; Cyclooxygenase 1; Drug Resistance; Genotype; Humans; Pharmacogenetics; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic
PubMed: 18429969
DOI: 10.1111/j.1365-2125.2008.03183.x -
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 -
Clinical Cardiology Apr 2013There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data.
HYPOTHESIS
PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events.
METHODS
PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis.
RESULTS
We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P<0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P=0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P=0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P=0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P=0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P=0.008).
CONCLUSIONS
Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events.
Topics: Adenosine Diphosphate; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Drug Resistance; Gastrointestinal Diseases; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Receptors, Purinergic P2Y12; Ticlopidine
PubMed: 23450832
DOI: 10.1002/clc.22094 -
Clinical and Applied... 2021Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in... (Meta-Analysis)
Meta-Analysis
Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in COVID-19 remains unknown. In this systematic review and meta-analysis, we performed a literature search using PubMed, EMBASE, and Cochrane Database to identify studies that reported the prevalence of systemic coagulopathy using established criteria in patients with COVID-19. The primary outcome was the prevalence of systemic coagulopathy (disseminated intravascular coagulation [DIC] and/or sepsis-induced coagulopathy [SIC]). Pooled prevalences and 95% confidence intervals [CIs] were calculated using random-effects model. A total of 5 studies including 1210 patients with confirmed COVID-19 were included. The pooled prevalence of systemic coagulopathy was 7.1% (95%CI: 3.2%,15.3%, I = 93%). The pooled prevalence of DIC (N = 721) and SIC (N = 639) were 4.3% (95%CI 1.7%, 10.4%, I = 84%) and 16.2% (95%CI: 9.3%, 26.8%, I = 74%), respectively. Only 2 studies reported the prevalence of elevated D-dimer levels with the pooled prevalence of 84.6% (95%CI: 52.0%,96.5%, I = 94%). Average D-dimer and fibrinogen levels were remarkably increased, while platelet counts, PT, and aPTT ratios were minimally affected in COVID-19. The estimated prevalence of systemic coagulopathy in patients with COVID-19 was low despite D-dimer elevation in most patients. Relatively low systemic coagulopathy in COVID-19 may contribute to the high incidence of thrombosis rather than bleeding in patients with COVID-19.
Topics: COVID-19; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Platelet Count; Prevalence; SARS-CoV-2; Sepsis; Thrombosis
PubMed: 33443456
DOI: 10.1177/1076029620987629 -
British Journal of Clinical Pharmacology Mar 2014The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this... (Meta-Analysis)
Meta-Analysis Review
AIM
The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this study was to conduct the first meta-analysis investigating the association between carriage of the PlA2 allele and resistance to currently licensed antiplatelet drugs.
METHODS
Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed effects and random effects models.
RESULTS
Sixteen studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n = 2318; 95% CI 0.743, 1.151; P = 0.481) was observed for resistance to any antiplatelet drug, OR 0.862 (n = 2085; 95% CI 0.685, 1.086; P = 0.208) for resistance to aspirin and OR 1.429 (n = 233; 95% CI 0.791, 2.582; P = 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed effects model when identified by the PFA-100 assay (n = 1151; OR 0.743, 95% CI 0.558, 0.989; P = 0.041) but with significant heterogeneity (I(2) = 55%; P = 0.002). Significance was lost with analysis using a random effects model.
CONCLUSIONS
The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated and standardized assays.
Topics: Drug Resistance; Gene Frequency; Genotype; Humans; Integrin beta3; Odds Ratio; Phenotype; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polymorphism, Genetic; Risk Factors
PubMed: 23834376
DOI: 10.1111/bcp.12204 -
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 -
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 -
Cerebrovascular Diseases (Basel,... 2022Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory...
INTRODUCTION
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus 2. It is characterized by thrombocytopenia, systemic activation of coagulation, extensive venous thrombosis, and anti-platelet factor 4 antibodies. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT, often associated with large vessel occlusion (LVO). Here, we describe a case of ischemic stroke with LVO after Ad26.COV2.S vaccine, then we systematically reviewed the published cases of ischemic stroke and VITT following COVID-19 vaccination.
METHODS
We describe a 58-year-old woman who developed a thrombotic thrombocytopenia syndrome with extensive splanchnic vein thrombosis and ischemic stroke due to right middle cerebral artery (MCA) occlusion, 13 days after receiving Ad26.COV2.S vaccination. Then, we performed a systematic review of the literature until December 3, 2021 using PubMed and EMBASE databases. The following keywords were used: ("COVID-19 vaccine") AND ("stroke"), ("COVID-19 vaccine") AND ("thrombotic thrombocytopenia"). We have selected all cases of ischemic stroke in VITT.
RESULTS
Our study included 24 patients. The majority of the patients were females (79.2%) and younger than 60 years of age (median age 45.5 years). Almost all patients (96%) received the first dose of an adenoviral vector-based vaccine. Ischemic stroke was the presenting symptom in 18 patients (75%). Splanchnic venous thrombosis was found in 10 patients, and cerebral venous thrombosis in 5 patients (21%). Most patients (87.5%) had an anterior circulation stroke, mainly involving MCA. Seventeen patients (71%) had an intracranial LVO. We found a high prevalence of large intraluminal thrombi (7 patients) and free-floating thrombus (3 patients) in extracranial vessels, such as the carotid artery, in the absence of underlying atherosclerotic disease. Acute reperfusion therapy was performed in 7 of the 17 patients with LVO (41%). One patient with a normal platelet count underwent intravenous thrombolysis with alteplase, while 6 patients underwent mechanical thrombectomy. A malignant infarct occurred in 9 patients and decompressive hemicraniectomy was performed in 7 patients. Five patients died (21%).
CONCLUSION
Our study points out that, in addition to cerebral venous thrombosis, adenoviral vector-based vaccines also appear to have a cerebral arterial thrombotic risk, and clinicians should be aware that ischemic stroke with LVO, although rare, could represent a clinical presentation of VITT.
Topics: Female; Humans; Male; Middle Aged; Ad26COVS1; COVID-19; COVID-19 Vaccines; Ischemic Stroke; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 35512656
DOI: 10.1159/000524290 -
Advances in Rheumatology (London,... Jun 2020Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of...
Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.
Topics: Antimalarials; Antiphospholipid Syndrome; Antirheumatic Agents; Arthritis, Rheumatoid; COVID-19; Chloroquine; Coronavirus Infections; Drug Eruptions; Drug Interactions; Female; Glucose; Heart Diseases; Humans; Hydroxychloroquine; Lipids; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Pandemics; Platelet Aggregation; Pneumonia, Viral; Pregnancy; Renal Insufficiency; Retinal Diseases; Sjogren's Syndrome
PubMed: 32517786
DOI: 10.1186/s42358-020-00134-8