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European Heart Journal. Cardiovascular... Jul 2023Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence...
Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.
Topics: Humans; Coronary Artery Disease; Fibrinolytic Agents; Blood Coagulation
PubMed: 37120728
DOI: 10.1093/ehjcvp/pvad032 -
The Cochrane Database of Systematic... Aug 2016Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016.
OBJECTIVES
We assessed the benefits and harms of thromboelastography (TEG)-guided or thromboelastometry (ROTEM)-guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far.
SEARCH METHODS
In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010.
SELECTION CRITERIA
We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta-analysis was not provided for continuous outcome data. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG- or ROTEM-guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA.
MAIN RESULTS
We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta-analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I(2) = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I(2) = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta-analyses also showed fewer participants with dialysis-dependent renal failure.We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I(2) = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I(2) = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG- or ROTEM-guided transfusion in bleeding patients.
AUTHORS' CONCLUSIONS
There is growing evidence that application of TEG- or ROTEM-guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.
Topics: Adult; Blood Coagulation Disorders; Cardiac Surgical Procedures; Child; Erythrocyte Transfusion; Hemorrhage; Humans; Liver Transplantation; Outcome Assessment, Health Care; Plasma; Randomized Controlled Trials as Topic; Thrombelastography
PubMed: 27552162
DOI: 10.1002/14651858.CD007871.pub3 -
Stroke Jun 2021Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND PURPOSE
Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke.
METHODS
We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model.
RESULTS
Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P<0.001, I2=0%).
CONCLUSIONS
As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.
Topics: Aspirin; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Time-to-Treatment
PubMed: 33902301
DOI: 10.1161/STROKEAHA.120.033033 -
Pediatric Blood & Cancer Mar 2023Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children... (Review)
Review
Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Treatment Outcome; Consensus
PubMed: 36579787
DOI: 10.1002/pbc.30173 -
Andrologia Mar 2021The updated systematic review and meta-analysis was conducted to assess the platelet indices between patients with varicocele and healthy subject. The main purpose of... (Meta-Analysis)
Meta-Analysis Review
The updated systematic review and meta-analysis was conducted to assess the platelet indices between patients with varicocele and healthy subject. The main purpose of our study was to explore the relationship between platelet and the pathogenesis of varicocele. Databases including Cochrane Library, PubMed, and MEDLINE were retrieved to identify studies. Two independent investigators extracted the related information of the included original passages. In order to estimate the difference of varicocele patients and healthy subjects, we applied the standardised mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs). 1,156 patients and 797 healthy subjects of nine studies met the pre-set inclusion criteria. The estimated SMD in MPV between varicocele patients and healthy subjects was 0.61 (95% CI: 0.29-0.93, p < 0.001). The estimated SMD in MPV between preoperative varicocele patients and post-operative varicocele patients was 0.22 (95% CI: 0.03-0.41, p = 0.02). The estimated SMD in PLT between varicocele patients and healthy subjects was -0.19 (95% CI: -0.28, -0.08, p = 0.001). The available data suggest that a higher MPV level in varicocele patients, and the varicocele operation can normalise the preoperatively elevated mean platelet volume levels. Further researches are needed to investigate the potential role of platelet with varicocele.
Topics: Blood Platelets; Humans; Male; Mean Platelet Volume; Platelet Count; Postoperative Period; Varicocele
PubMed: 33369777
DOI: 10.1111/and.13939 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
American Journal of Obstetrics &... Jul 2023Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a systematic review and meta-analysis to evaluate the association in pooled samples and in detail.
DATA SOURCES
A systematic literature search was performed using Medline, Embase, ScienceDirect, Web of Science, Cochrane Library, NICHD-DASH, LILACS, and Scopus from inception to April 22, 2022.
STUDY ELIGIBILITY CRITERIA
Observational studies comparing platelet count between women with preeclampsia and normotensive pregnant women were included.
METHODS
The mean differences with 95% confidence interval in platelet count were calculated. Heterogeneity was assessed using I statistics. Sensitivity and subgroup analyses were conducted. Statistical analysis was performed using RevMan 5.3 and ProMeta 3 software.
RESULTS
A total of 56 studies comprising 4892 preeclamptic and 9947 normotensive pregnant women were included. Meta-analysis showed that platelet count was significantly lower in women with preeclampsia than in normotensive controls (overall: mean difference, -32.83; 95% confidence interval, -40.13 to -25.52; P<.00001; I=92%; mild preeclampsia: mean difference, -18.65; 95% confidence interval, -27.17 to -10.14; P<.00001; I=84%; severe preeclampsia: mean difference, -42.61; 95% confidence interval, -57.53 to -27.68; P<.00001; I=94%). Significantly lower platelet count was also observed in the second trimester (mean difference, -28.84; 95% confidence interval, -44.59 to -13.08; P=.0003; I=93%), third trimester (mean difference, -40.67; 95% confidence interval, -52.14 to -29.20; P<.00001; I=92%), and before the diagnosis of preeclampsia (mean difference, -18.81; 95% confidence interval, -29.98 to -7.64; P=.009; I=87%), but not in the first trimester (mean difference, -15.14; 95% confidence interval, -37.71 to 7.43; P=.19; I=71%). Overall, the pooled sensitivity and specificity of platelet count were 0.71 and 0.77, respectively. The area under the curve was 0.80.
CONCLUSION
This meta-analysis confirmed that platelet count was significantly lower in preeclamptic women, irrespective of severity and presence or absence of associated complications, even before the onset of preeclampsia and in the second trimester of pregnancy. Our findings suggest that platelet count may be a potential marker to identify and predict preeclampsia.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Platelet Count; Blood Pressure; Pregnancy Trimester, First; Pregnancy Trimester, Third
PubMed: 37098392
DOI: 10.1016/j.ajogmf.2023.100979 -
International Journal of Cardiology Aug 2014Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV.
METHODS
Medline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data.
RESULTS
Forty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70 fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84 fL (95% CI: 0.63, 1.04) and 0.46 fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥7.3 fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58).
CONCLUSION
Larger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.
Topics: Coronary Artery Disease; Cross-Sectional Studies; Humans; Mean Platelet Volume; Observational Studies as Topic; Platelet Count; Risk Factors
PubMed: 25017904
DOI: 10.1016/j.ijcard.2014.06.028 -
European Journal of Pediatrics Aug 2023Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly... (Meta-Analysis)
Meta-Analysis Review
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
Topics: Infant, Newborn; Humans; Infant, Premature; Hemorrhage; Enterocolitis, Necrotizing; Thrombocytopenia; Sepsis
PubMed: 37258776
DOI: 10.1007/s00431-023-05031-y -
Journal of the American Society of... Jul 2021Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on...
BACKGROUND
Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.
METHODS
To help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.
RESULTS
We included 73 studies in the systematic review to assess CKD's overall effect on platelet function in patients; 11 of them described CKD's effect on platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ; analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.
CONCLUSIONS
Overall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.
PubMed: 33941607
DOI: 10.1681/ASN.2020101440