Platelet Function Research Articles

Platelet Reactivity with MACE in Acute Coronary Syndrome Patients Post-PCI under Dual Antiplatelet Therapy: A Meta-Analysis.

Aim/Background Acute coronary syndrome (ACS), a condition characterized by acute cardiac ischemia, is among the major causes of death from cardiovascular diseases (CVD). However, whether there is a correlation between platelet reactivity and major adverse cardiovascular events (MACE) remains debatable, and whether platelet function tests should be tailored for ACS patients after percutaneous coronary intervention (PCI) is still under discussion. This study aims to investigate the relationship between platelet reactivity and the occurrence of MACE in ACS patients post-PCI and to discuss the implications of these findings. Methods Clinical studies on 'PCI, ACS, dual antiplatelet therapy (DAPT), platelet reactivity, major adverse cardiovascular events (MACE)' up to 31 October 2023, were systematically collected from Embase, PubMed, and the Cochrane Library. Twelve articles meeting predefined criteria were selected. Meta-analysis was performed using Review Manager 5.4 (Cochrane, London, UK) and Stata 15.0 (StataCorp LLC, College Station, TX, USA) to compute pooled effect sizes, assess heterogeneity, explore sources of heterogeneity, and evaluate publication bias. Results Twelve articles consisting of 9297 patients were included. The meta-analysis showed that ACS patients with high platelet reactivity (HPR) who received PCI and used DAPT for 1-2 years had a greater risk of MACE (risk ratio (RR) = 1.79, 95% confidence interval (CI): 1.30-2.46) compared to those with low platelet reactivity. Moreover, greater platelet reactivity was associated independently with all-cause mortality (RR = 2.26, 95% CI: 1.63-3.12), cardiac mortality (RR = 2.87, 95% CI: 2.16-3.8), myocardial infarction (RR = 1.98, 95% CI: 1.53-2.5), in-stent restenosis (RR = 1.87, 95% CI: 1.22-2.87), as well as stroke (RR = 1.62, 95% CI: 1.02-2.57), but not with coronary revascularization events (RR = 0.99, p = 0.96, 95% CI: 0.80-1.24). On the other hand, meta-regression revealed that region (p = 0.99), type of ACS patient (p = 0.16), drug regimen (p = 0.48), testing method (p = 0.51), sampling time (p = 0.70), follow-up time (p = 0.45), and PCI protocol (p = 0.27) were not sources of heterogeneity in the study. Conclusion The meta-analysis outcomes indicate that in ACS patients receiving PCI and using dual antiplatelet therapy for 1-2 years, HPR was independently positively correlated with major adverse cardiovascular events, all-cause (or cardiac) mortality, recurrent myocardial infarction, in-stent restenosis, and stroke. This suggests that platelet reactivity testing has clinical and translational significance in predicting patients' risk of adverse cardiovascular events.

CHARACTERISTICS AND OUTCOME OF LEFT MAIN STEM PCI AMONG WOMEN

Left main stem disease is a severe condition affecting a major coronary artery, traditionally treated with coronary artery bypass grafting. Recent advancements in percutaneous coronary intervention have made it a viable option, particularly for women who face unique risks and outcomes compared to men. Objective: This study aims to evaluate the characteristics and outcomes of percutaneous coronary intervention for left main stem disease in female patients, focusing on procedural outcomes and changes in laboratory parameters before and after the intervention. Methods: A prospective observational study was conducted from January to July 2024 with 68 female patients, aged 18 and above, from Fauji Foundation Hospital Rawalpindi. Various percutaneous coronary intervention techniques were used, and data on ejection fractions, access methods, and procedural specifics were collected. Pre- and post-procedural laboratory outcomes including haemoglobin, creatinine, platelet counts, and alanine aminotransferase levels were analyzed. Results: The mean age of participants was 63.6 years. Diabetes, hypertension, and dyslipidemia were common comorbidities. Laboratory results showed stable haemoglobin levels, slight increases in creatinine, and consistent platelet counts and ALT levels post-procedure. Statistical analysis revealed no significant changes in these parameters, indicating minimal impact on anaemia, renal function, and platelet or liver function. Conclusion: percutaneous coronary intervention for the left main stem in females generally results in stable laboratory outcomes with minimal impact on anaemia, renal function, and platelet or liver function. The procedure is safe with a low mortality rate. Continuous monitoring is recommended to manage any potential complications effectively.

Effect of Selected Crystalloid and Colloid Solutions on Coagulation Status Evaluated by Rotational Thromboelastometry and Platelet Function Analyser: An in vitro Study

Introduction: Crystalloid and colloid solutions commonly used in intensive and perioperative care can affect haemocoagulation status. This in vitro study assessed the impact of Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions on primary and secondary haemostasis using rotational thromboelastometry and platelet function analyser. Methods: In this prospective study, we examined blood samples from 20 healthy volunteers using rotational thromboelastometry and platelet function analyser. Simultaneously, we analysed the blood samples subjected to 10% dilution using Plasma-Lyte, albunorm 5%, and Gelaspan 4% solutions. Results: Compared to controls, Plasma-Lyte shortened EXTEM-CT (p = 0.005) and reduced FIBTEM-MCF (p = 0.017). albunorm 5% prolonged EXTEM-CFT (p = 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p = 0.038, p = 0.001, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also prolonged EXTEM-CFT (p < 0.001), decreased EXTEM-alpha (p < 0.001) and MCF in EXTEM, INTEM, and FIBTEM tests (p < 0.001, p < 0.001, p = 0.009, respectively), along with MCE in the PLTEM test (p < 0.001). Gelaspan 4% also reduced EXTEM-CT (p = 0.021). All solution prolonged CT in PFA Col/ADP (p = 0.003 for Plasma-Lyte, p < 0.001 for albunorm and Gelaspan) and albunorm 5% also prolonged CT in Col/Epi (p = 0.003). Conclusion: Plasma-Lyte had the least effect on secondary haemostasis, whereas albunorm 5% had the least effect among colloids. Gelaspan 4% adversely affected the propagation phase of coagulation, maximal strength and elasticity of the coagulum, and the level of functional fibrinogen. All solutions adversely affected platelet function in primary haemostasis, with Plasma-Lyte showing the least effect.

Pharmacological Actions of Adapalene on Platelet Function and Thrombosis through the PI3K/AKT Signaling Pathway

Pharmacological Actions of Adapalene on Platelet Function and Thrombosis through the PI3K/AKT Signaling Pathway

Mepacrine Flow Cytometry Assay for the Diagnosis of Platelet δ-granule Defects: Literature Review on Methods-Towards a Shared Detailed Protocol.

Accurate assessment of platelet secretion is essential for the diagnosis of inherited or acquired platelet function disorders and more specifically in identifying δ-storage pool disease. Mepacrine, a fluorescent dye, specifically accumulates in platelet δ-granules. The mepacrine flow cytometry (mepacrine FCM) assay has been used for more than half a century in the clinical laboratory as a diagnostic tool for platelet δ-granule disorders. The assay requires a small volume of blood, can be performed in thrombocytopenic patients, provides rapid assessment of δ-granule content and secretion, and, thus, enables differentiation between storage and release defects. There is however a broad heterogeneity in methods, reagents, and equipment used. Lack of standardization and limited data on analytical and clinical performances have led the 2022 ISTH SSC (International Society on Thrombosis and Haemostasis Scientific and Standardization Committee) Subcommittee on Platelet Physiology expert consensus to rate this assay as simple but of uncertain value. Yet, the data used by experts to formulate the recommendations were not discussed and even not mentioned. Guidance for laboratory studies of platelet secretion assay would be very helpful for clinical laboratories and health authorities especially considering the implications of the new In Vitro Diagnostic Regulation in Europe. The purpose of the present work was to review the reported methodologies for the mepacrine FCM assay and to offer an example of detailed protocol. This would help standardization and pave the way for more rigorous comparative studies.

Hydrogel encapsulating gold nanoparticles for targeted delivery of nitroglycerin to reduce post-cardiac dysfunction inflammation by inhibiting the Wnt/β-catenin signaling pathway.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) stainingrevealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction.

The effect of concurrent clopidogrel and omeprazole administration on clopidogrel metabolism and platelet function in healthy cats.

Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown. We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats. Ten domestic cats. In this 2-sequence, 2-period, 2-treatment randomized crossover study, healthy cats were randomly assigned to receive clopidogrel only (18.75 mg PO q24h) or clopidogrel with omeprazole (1 mg/kg PO q12h) for 10 days, followed by a 2-week washout period, and then the opposite treatment for another 10 days. Blood was collected by jugular venipuncture on days 0, 5, and 10. Plasma CAM concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate Analyzer, and Platelet Function Analyzer-100 (PFA-100). Multiplate Analyzer and PFA-100 detected no difference in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < .001) in platelet function from day 0 to 5 and day 0 to 10 in both treatment groups but no difference between treatment groups. Plasma CAM concentrations were significantly lower on day 10 (P < .02) in cats receiving both medications versus clopidogrel only. Concurrent omeprazole and clopidogrel administration was associated with altered pharmacokinetics on day 10, but no difference in pharmacodynamics between the 2 treatment groups. The short-term use of clopidogrel and omeprazole does not seem to alter platelet function significantly.

Assay variables and early clinical evaluation of low-angle light scattering for platelet function analysis.

The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting. Platelet aggregation was induced by ADP in diluted PRP in the presence of 2mM calcium at 23°C. The study included healthy adults (n = 30), healthy children (n = 20), and pediatric patients with suspected or diagnosed platelet function abnormalities (n = 25). The assay parameters were stable for at least 3h after isolation of PRP and were sensitive to plasma dilution in the range of 2-8%. The initial aggregation velocity was significantly reduced in pediatric patients compared with healthy children (p < 0.05). ADP-induced light transmission amplitude was moderately correlated with LaSca amplitude of aggregation in healthy children (p = 0.52, p < 0.05) but not in pediatric patients. We standardized the protocol for platelet aggregation assessment by LaSca and characterized the influence of preanalytical and analytical variables on it.

Thromboelastography with Platelet Mapping to Optimize Surgical Timing in Coronary Artery Bypass Grafting Patients on P2Y12 Receptor Blockers Therapy.

An increasing number of patients attending coronary artery bypass grafting (CABG) receive preoperative antiplatelet drugs (acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor). The optimal assessment of preoperative platelet function is the aim of this study for a shorter surgical timing in patients undergoing elective coronary artery bypass grafting. This study was performed on patients presenting for first-time isolated CABG on therapy with an P2Y12 receptor blockers loading dose (clopidogrel [300 mg] or prasugrel [60 mg] or ticagrelor [180 mg]) or P2Y12 receptor blockers maintenance therapy at least for five days (clopidogrel [75 mg once daily], prasugrel [10 mg once daily], ticagrelor [90 mg twice daily]). All patients received simultaneously acetylsalicylate acid (100 mg daily). Exclusion criterion was emergency CABG regardless of preoperative antiplatelet and anticoagulant therapy. All patients' data were recorded in an Excel® file and analyzed using RStudio® software. Forty-eight consecutive adult patients presenting for CABG were enrolled. Preoperative thromboelastography-platelet mapping showed platelet resistance to P2Y12 blockers receptor - 25% for clopidogrel (6/24), 33% for ticagrelor (6/18), 33% for prasugrel (2/6), and this data was useful to obtain a shorter CABG waiting time in comparison with current guidelines (2.7 vs. five days for clopidogrel, 2.5 vs. five days for ticagrelor, 3.3 vs. seven days for prasugrel). Preoperative thromboelastography-platelet mapping is helpful to detect harmful P2Y12 receptor blockers resistance and to minimize CABG waiting time avoiding unnecessary and life-threatening delays.

Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.

Double C2-like domain beta (DOC2B) is a vesicle priming protein critical for glucose-stimulated insulin secretion in β-cells. Individuals with type 1 diabetes (T1D) have lower levels of DOC2B in their residual functional β-cell mass and platelets, a phenotype also observed in a mouse model of T1D. Thus, DOC2B levels could provide important information on β-cell dys(function). Our objective was to evaluate the DOC2B secretome of β-cells. In addition to soluble extracellular protein, we assessed DOC2B localized within membrane-delimited nanoparticles - extracellular vesicles (EVs). Moreover, in rat clonal β-cells, we probed domains required for DOC2B sorting into EVs. Using Single Extracellular VEsicle Nanoscopy, we quantified EVs derived from clonal β-cells (human EndoC-βH1, rat INS-1 832/13, and mouse MIN6); two other cell types known to regulate glucose homeostasis and functionally utilize DOC2B (skeletal muscle rat myotube L6-GLUT4myc and human neuronal-like SH-SY5Y cells); and human islets sourced from individuals with no diabetes (ND). EVs derived from ND human plasma, ND human islets, and cell lines were isolated with either size exclusion chromatography or differential centrifugation. Isolated EVs were comprehensively characterized using dotblots, transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting. DOC2B was present within EVs derived from ND human plasma, ND human islets, and INS-1 832/13 β-cells. Compared to neuronal-like SH-SY5Y cells and L6-GLUT4myc myotubes, clonal β-cells (EndoC-βH1, INS-1 832/13, and MIN6) produced significantly more EVs. DOC2B levels in EVs (over whole cell lysates) were higher in INS-1 832/13 β-cells compared to L6-GLUT4myc myotubes; SH-SY5Y neuronal-like cells did not release appreciable DOC2B. Mechanistically, we show that DOC2B was localized to the EV lumen; the tandem C2 domains were sufficient to confer sorting to INS-1 832/13 β-cell EVs. Clonal β-cells and ND human islets produce abundant EVs. In cell culture, appreciable DOC2B can be packaged into EVs, and a small fraction is excreted as a soluble protein. While DOC2B-laden EVs and soluble protein are present in ND plasma, further studies will be necessary to determine if DOC2B originating from β-cells significantly contributes to the plasma secretome.

PROTACs in platelets: emerging antithrombotic strategies and future perspectives.

Proteolysis-targeted chimeras (PROTACs) are heterobifunctional compounds that selectively target proteins for degradation and are an emerging therapeutic modality to treat diseases such as cancer and neurodegenerative disorders. This review will widen the area of application by highlighting the ability of PROTACs to remove proteins from the anucleate platelets and evaluate their antithrombotic potential. Proteomic and biochemical studies demonstrated that human platelets possess the Ubiquitin Proteasomal System as well as the E3 ligase cereblon (CRBN) and therefore may be susceptible to PROTAC-mediated protein degradation. Recent findings confirmed that CRBN ligand-based PROTACs targeting generic tyrosine kinases, Btk and/or Fak lead to efficacious and selective protein degradation in human platelets. Downregulation of Btk, a key player involved in signalling to thrombosis, but not haemostasis, resulted in impaired in-vitro thrombus formation. Platelets are susceptible to targeted protein degradation by CRBN ligand-based PROTACs and have limited ability to resynthesise proteins, ensuring long-term downregulation of target proteins. Therefore, PROTACs serve as an additional research tool to study platelet function and offer new therapeutic potential to prevent thrombosis. Future studies should focus on enhancing cell specificity to avoid on-target side effects on other blood cells.

Imperatorin reduces thrombus formation by inhibiting platelet function and phosphoproteins

Imperatorin reduces thrombus formation by inhibiting platelet function and phosphoproteins

Preoperative Depression is Associated With a Higher Risk of Bleeding in Type a Aortic Dissection Repair: A Population Study of National Inpatient Sample From 2015-2020.

Depression is highly prevalent in patients with aortic diseases. While depression has been shown to predispose patients to adverse outcomes after surgery, its impact on postoperative outcomes in Stanford Type A Aortic Dissection (TAAD) has not been established. This study aimed to conduct a population-based examination of the effect of preoperative depression on in-hospital outcomes after TAAD using the National/Nationwide Inpatient Sample (NIS) database, the largest all-layer database in the US. Patients undergoing TAAD repair were identified in NIS from the last quarter of 2015-2020. Multivariable logistic regressions were used to compare in-hospital outcomes between patients with and without preoperative depression, adjusted for demographics, comorbidities, hospital characteristics, primary payer status, and transfer status. There were 321 (7.50%) patients with depression and 3961 (92.50%) non-depressive patients who underwent TAAD repair. Patients with and without depression had comparable in-hospital mortality (11.84% vs 15.37%, P = 0.35). However, Patients with depression had a higher risk of hemorrhage/hematoma (83.49% vs 76.6%, aOR 1.593, 95 CI 1.161-2.184, P < 0.01) and a higher rate of transfer out (40.81% vs 32.62%, aOR 1.396, 95 CI 1.077-1.81, P = 0.01). All other in-hospital complications, hospital length of stay (LOS), and total hospital charge were comparable between patients with and without depression. Preoperative depression is associated with a higher risk of bleeding after TAAD repair. This may be due to anti-depression treatment, such as Selective Serotonin Reuptake Inhibitors (SSRIs), that can disrupt platelet function and lead to abnormal bleeding. While depression is not associated with other major outcomes, preoperative depression screening, as well as hemostatic monitoring and appropriate blood management in patients with depression may be crucial in preventing bleeding complications in TAAD repair.

The role of platelets and megakaryocytes in sepsis and ARDS.

Since the global COVID-19 pandemic, there has been a renewed focus on lung injury during infection. Systemic inflammatory responses such as acute respiratory distress syndrome (ARDS) and sepsis are a leading cause of morbidity and mortality for both adults and children. Improvements in clinical care have improved outcomes but mortality remains ∼40% and significant morbidity persists for those patients with severe disease. Mechanistic studies of the underlying biological processes remain essential to identifying therapeutic targets. Furthermore, methods for identifying the underlying drivers of organ failure are key to treating and preventing tissue injury. In this review, we discuss the contribution of megakaryocytes (MKs) and platelets to the pathogenesis of systemic inflammatory syndromes. We explore the role of MKs and the new identification of extramedullary MKs during sepsis. We describe the alterations in the platelet transcriptome during sepsis. Lastly, we explore platelet function as defined by aggregation, activation and the formation of heterotypic aggregates. Much more work is necessary to explore the contribution of platelets to these heterogenous syndromes, but the foundation of platelets as key contributors to inflammation has been laid.

Increased platelet-leucocyte complexes do not result in coagulation activation in plateletpheresis donors.

Although plateletpheresis donation is commonly accepted as a safe procedure, its influence on platelet function, coagulation system and fibrinolysis is not completely elucidated. In this study, we tried to assess the effects of plateletpheresis on donor's hemostasis system by measuring platelet activation, development of platelet-leukocyte aggregates, and coagulation activation. Prospective observational study. We used flow cytometry to determine the levels of platelet-monocyte complexes (PMC) and platelet-neutrophil complexes (PNC). sP-selectin and prothrombin fragment (PF) 1 + 2 values were determined by ELISA. The PMC levels increased significantly seven days after apheresis in comparison with just after apheresis and 24 h after apheresis (p < 0.05). The PNC levels increased significantly seven days after apheresis compared to immediately after apheresis (p < 0.05). sP-selectin values decreased significantly immediately after apheresis (p < 0.05). While sP-selectin values increased seven days after apheresis in comparison with immediately after apheresis and 24 h after apheresis, but there were not statistically significant differences for sP-selectin levels (p > 0.05). PF1 + 2 levels decreased significantly immediately after apheresis compared to pre-apheresis (p < 0.05) and increased 24 h after apheresis and seven days after apheresis, but these differences were not statistically significant. We concluded that plateletpheresis affects platelet activation but does not cause any change in coagulation activation.

Distinct role of GRK3 in platelet activation by desensitization of G protein-coupled receptors.

Many platelet agonists mediate their cellular effects through G protein-coupled receptors (GPCRs) to induce platelet activation, and GPCR kinases (GRKs) have been demonstrated to have crucial roles in most GPCR functions in other cell types. Here, we investigated the functional role of GRK3 and the molecular basis for the regulation of GPCR desensitization by GRK3 in platelets. We used mice lacking GRK3 as well as β-arrestin2 which has been shown to be important in GPCR function in platelets. Platelet aggregation and dense granule secretion induced by 2-MeSADP, U46619, thrombin, and AYPGKF were significantly potentiated in both GRK3 -/- and β-arrestin2 -/- platelets compared to wild-type (WT) platelets, while non-GPCR agonist collagen-induced platelet aggregation and secretion were not affected. We have previously shown that GRK6 is not involved in the regulation of Gq-coupled 5HT2A and Gz-coupled a2A adrenergic receptors. Interestingly, in contrast to GRK6, platelet aggregation induced by co-stimulation of serotonin and epinephrine which activate 5-HT2A and a2A adrenergic receptors, respectively, was significantly potentiated in GRK3 -/- platelets, suggesting that GRK3 was involved in general GPCR regulation. In addition, platelet aggregation in response to the second challenge of ADP was restored in GRK3 -/- platelets whereas re-stimulation of the agonist failed to induce aggregation in WT platelets, confirming that GRK3 contributes to general GPCR desensitization. Finally, 2-MeSADP- and AYPGKF-induced AKT and ERK phosphorylation were significantly potentiated in GRK3 -/- platelets. GRK3 plays a crucial role in the regulation of platelet activation through general GPCR desensitization in platelets.

PAR for the liver course: Preserving platelet function mitigates outcomes in cirrhosis.

PAR for the liver course: Preserving platelet function mitigates outcomes in cirrhosis.

Platelet Function, Platelet Size and Content of Reticulated Platelets: Interactions in Patients Receiving Dual Antiplatelet Therapy.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy.

Effects of selective serotonin reuptake inhibitors on platelet functions: a literature review.

Many epidemiological studies have evidenced an increased bleeding risk associated with selective serotonin reuptake inhibitors (SSRIs), yet the underlying mechanisms remain unclear. This review summarizes data on SSRIs' effects on platelet functions assessed with assays used in clinical practice and highlights the areas that deserve further investigation. Conflicting results of SSRI effects on platelet aggregation were observed irrespectively of the agonist used, the antidepressant drug or the study type. Alike, discrepant results were reported with flow-cytometry-based assays assessing either platelet surface glycoprotein levels, integrin activation, agonist-induced secretion of intraplatelet granule content or membrane anionic phospholipid exposure. Other tests may have detected a platelet function defect in SSRIs samples, however, results were largely inconsistent. Critical literature examination unveils very low certainty of evidence on potential SSRI effect on platelet functions. Findings are often inconsistent even when similar methods are used, most likely because of differences in study design, included patients (age, comorbid conditions), SSRIs' type and dose, uncontrolled confounding factors, and statistical analysis power. Further studies are needed to disentangle any intrinsic antiplatelet effect of SSRIs and the multiple confounding factors, mainly the depression control itself and the degree of platelet SERT inhibition.

Outcome of tailored antiplatelet therapy in carotid stenting: a retrospective comparative study

BackgroundCarotid stenting requires dual antiplatelet therapy to effectively prevent thromboembolic complications. However, resistance to clopidogrel, a key component of this therapy, may lead to persistent risk of these complications. The aim of this study was to determine, if the implementation of routine platelet function testing and adjusting therapy was associated with lower incidence of thromboembolic complications and death.MethodsAll consecutive patients treated with carotid artery stenting in a single institution over 8 years were enlisted in a retrospective study. Platelet function testing was performed, and efficient antiplatelet therapy was set before the procedure. Incidence of procedure-related stroke or death within periprocedural period (0–30 days) was assessed. The results were evaluated in relation to the findings of six prominent randomized control trials.ResultsA total of 241 patients were treated for carotid stenosis, seven patients undergo CAS on both sides over time. There was 138 symptomatic (55,6%) and 110 asymptomatic stenoses (44,4%). Five thromboembolic complications (2,01%) occurred, four of them (1,61%) was procedure-related. Two patients died because of procedure-related stroke (0,82%). Incidence of procedure-related stroke or death was significant lower compared to the results of CREST study (2,01% vs. 4,81%, P = 0,0243) in the entire cohorts, and to the results of ICSS study in the symptomatic cohorts (2,86% vs. 7,37%, P = 0,0243), respectively.ConclusionsTailored antiplatelet therapy in carotid stenting is safe and seems to be related with lower incidence of procedure-related death or stroke rate. Larger prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard dual antiplatelet should be considered.