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Background: Rheumatoid arthritis (RA)-associated disease activity is accompanied by abnormalities in the coagulation-fibrinolysis system, potentially increasing the risk of venous and arterial thromboembolism. The aim of this case-control study was to evaluate the hemostatic system functions in a group of RA patients by whole blood rotation thromboelastometry and impedance aggregometry.   Methods: Whole blood rotation thromboelastometry and impedance aggregometry were performed in RA patients (cases) treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and compared 1:1 with age (± 3 yrs) and sex-matched healthy individuals (controls). In each enrolled participant, global coagulation monitoring was assessed by whole blood rotational thromboelastometry (ROTEM®, Instrumentation Laboratory-Werfen) and whole blood impedance aggregometry (Multiplate® Analyser, Roche Diagnostics) tests. Variables assessing disease activity, demographics and cardiovascular risk were assessed. Univariate analyses (independent T-test, Pearson correlation) were performed.   Results: The study population included 30 RA patients on b/tsDMARDs and 30 controls. The cases (mean age 56.2±11.6 years, 90% female) had a mean disease duration of 17.8±9.1 years; most received methotrexate (60%) and low-dose prednisone (1.2±2.1 mg/day); NSAIDs were used by 47%. No participants were taking antiplatelet or anticoagulant medications. Disease activity and inflammatory markers were generally low (SDAI: 10.1±8, CRP 3.5±4.3 mg/L, ESR 23±18.5 mm/h). A history of VTE was reported in 7% of patients, while no previous MACE events were documented. Regarding cardiovascular risk factors: 10% were current smokers, 53% had hypercholesterolaemia, 27% had hypertension and only one patient had diabetes mellitus. Thromboelastometry and aggregometry showed excellent internal validity, as several measurements significantly and strongly correlated with inflammatory markers, disease activity, and lipids (Figure 1). In INTEM, EXTEM and FIBTEM tests, maximum clot firmness (MCF) was significantly increased in RA patients compared with controls (p<0.001 in all three comparisons) (Table 1). A significant difference in platelet aggregation was found between RA patients and healthy controls in each of the tests considered (Table 1). Patients taking glucocorticoids at the time of blood sampling had MCF in INTEM and EXTEM significantly higher than those patients who were not (p=0.011 and p=0.020, respectively; Table 2). Thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly higher in patients taking oral glucocorticoids than in those who were not (p=0.0006; Table 2). Use of NSAIDs did not affect outcomes. Analysis of data stratified by type of drug used is still in progress.   Conclusions: Hypercoagulability can be detected by whole blood thromboelastometry and impedance aggregometry in RA patients and correlates with disease activity. The clinical implication of these findings deserves further investigations.

Acute aortic dissection type A (AADA) is a life-threatening surgical emergency with high mortality. Use of antiplatelet drugs and/or platelet dysfunction are associated with higher rates of postoperative morbidity and mortality.1 However, studies on impact of platelet dysfunction in this patient group is limited. The aim of this study was to determine the relationship between preoperative platelet function assessed by Multiplate® aggregometry and transfusion requirement. This prospective observational study included 180 patients over a two-year period (2019–2021) who underwent emergency surgical repair of AADA. AADA patients with iatrogenic causes (n = 8) were excluded. Platelet function was evaluated prior to surgery using Multiplate® analyzer and three activators, namely adenosine diphosphate (ADP test), arachidonic acid (ASPI test) and thrombin receptor-activating peptide-6 (TRAP test). Platelet aggregometry is used to assess the effect of antiplatelet drugs such as Aspirin (ASPI test), ADP-antagonists like clopidogrel (ADP test) and GpIIbIIIa receptor antagonists (TRAP test). The number of blood products transfused, need for surgical re-exploration, length of hospital stay, mortality and survival were compared. An abnormal aggregation response was observed in 88 (48.9%) patients using ASPI test, in 43 (23.9%) patients using ADP test and in 112 (62.2%) patients using the TRAP test. 31 (17.2%) patients had an abnormal response to all three tests. Preoperative Aspirin use was reported in 35 (19.4%) while clopidogrel use was reported in 7 (3.9%). Patients with low ASPI response received more red cell concentrates (9.5 ± 7.3 vs 6.2 ± 4.5, p = 0.007) and platelet concentrates (5.9 ± 3.5 vs 4.8 ± 2.7, p = 0.038) whereas patients with low ADP tests received more red cell concentrates (9.6 7.2 vs 7.1 5.7, p = 0.014). There were no statistically significant differences in the need for surgical re-exploration, the total length of hospital stay, mortality, or survival time. Our results show that AADA patients with abnormal aggregation response require more red cell and platelet concentrate transfusions. Multiplate® aggregometry can be a useful indicator of platelet dysfunction and bleeding risk in AADA patients.

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

Platelet function testing is essential for the diagnosis of hemostasis disorders. While there are many methods used to test platelet function for research purposes, standardization is often lacking, limiting their use in clinical practice. Light transmission aggregometry has been the gold standard for over 60 years, with inherent challenges of working with live dynamic cells in specialized laboratories with independent protocols. In recent years, standardization efforts have brought forward fully automated systems that could lead to more widespread use. Additionally, new technical approaches appear promising for the future of specialized hematology laboratories. This review presents developments in platelet function testing for clinical applications.

Atherosclerotic cardiovascular disease is the leading cause of death in developed countries. Therefore, there is an increasing interest in developing new potent and safe antiplatelet agents. Coumarins are a family of polyphenolic compounds with several pharmacological activities, including platelet aggregation inhibition. However, their antiplatelet mechanism of action needs to be further elucidated. The aim of this study is to provide insight into the biochemical mechanisms involved in this activity, as well as to establish a structure–activity relationship for these compounds. With this purpose, the antiplatelet aggregation activities of coumarin, esculetin and esculin were determined in vitro in human whole blood and platelet-rich plasma, to set the potential interference with the arachidonic acid cascade. Here, the platelet COX activity was evaluated from 0.75 mM to 6.5 mM concentration by measuring the levels of metabolites derived from its activity (MDA and TXB2), together with colorimetric assays performed with the pure recombinant enzyme. Our results evidenced that the coumarin aglycones present the greatest antiplatelet activity at 5 mM and 6.5 mM on aggregometry experiments and inhibiting MDA levels.

Flavonoids are compounds with a benzopyranic structure that exhibits multiple pharmacological activities. They are known for their venotonic activity, but their mechanism of action remains unclear. It is thought that, as this mechanism is mediated by prostaglandins, these compounds may interfere with the arachidonic acid (AA) cascade. These assays are designed to measure the antiplatelet aggregation capacity of quercetin, rutin, diosmetin, diosmin, and hidrosmin, as well as to evaluate a potential structure−activity ratio. In this paper, several studies on platelet aggregation at different concentrations (from 0.33 mM to 1.5 mM) of different flavone compounds are conducted, measuring platelet aggregation by impedance aggregometry, and the cyclooxygenase (COX) activity by metabolites generated, including the activity of the pure recombinant enzyme in the presence of these polyphenols. The results obtained showed that quercetin and diosmetin aglycones have a greater antiplatelet effect and inhibit the COX enzyme activity to a greater extent than their heterosides; however, the fact that greater inhibition of the pure recombinant enzyme was achieved by heterosides suggests that these compounds may have difficulty in crossing biological membranes. In any case, in view of the results obtained, it can be concluded that flavonoids could be useful as coadjuvants in the treatment of cardiovascular pathologies.

Background： Several platelet function tests are currently used to measure responsiveness to antiplatelet therapy. This study was to compare two tests, light transmittance aggregometry （LTA） and modified thrombelastography （mTEG）, for predicting clinical outcomes in Chinese patients after percutaneous coronary intervention （PCI）. Methods： Prospective, observational, single-center study of 789 Chinese patients undergoing PCI was enrolled. This study was investigated the correlations between the two tests and performed receiver operating characteristic curve （ROC） analysis for major adverse cardiovascular events （MACEs） at 1-year follow-up. Results： MACEs occurred in 32 patients （4.1%）. Correlations were well between the two tests in the adenosine diphosphate induced platelet reactivity （Spearman r = 0.733, P 〈 0.001 ）. ROC-curve analysis demonstrated that LTA （area under the curve [AUC]： 0.677; 95% confidence interval [CO： 0.643-0.710; P = 0.0009）, and mTEG （AUC： 0.684; 95% CI： 0.650-0.716; P = 0.0001） had moderate ability to discriminate between patients with and without MACE. MACE occurred more frequently in patients with high on-treatment platelet reactivity （HPR） when assessed by LTA （7.4% vs. 2.7%; P 〈 0.001）, and by TEG （6.7% vs. 2.6%; P 〈 0.001 ）. Kaplan-Meier analysis demonstrated that HPR based on the LTA and mTEG was associated with almost 3-fold increased risk of MACE at 1-year follow-up. Conclusions： The correlation between LTA and mTEG is relatively high in Chinese patients. HPR measured by LTA and mTEG were significantly associated with MACE in Chinese patients undergoing PCI.

PurposeObese patients exhibit an overall increased platelet reactivity and a reduced sensitivity to antiplatelet therapy. The aim of this study is to evaluate the platelet reactivity measured by impedance aggregometry in overweight and obese patients and chronic coronary syndrome (CCS) that were treated with dual antiplatelet therapy (DAPT).MethodsPlatelet aggregation was assessed by impedance aggregometry in patients with CCS receiving DAPT (aspirin plus clopidogrel). We compared the platelet reactivity in patients with a normal weight versus overweight or obese patients. Furthermore, the correlation between the body mass index (BMI) and adenosine diphosphate- (ADP-) or thrombin receptor-activating peptide- (TRAP-) dependent platelet aggregation was analyzed.Results64 patients were included in the study of which 35.9% were patients with normal weight. A higher ADP- and TRAP-dependent platelet reactivity was observed in overweight and obese patients (ADP: median 27 units (U) [IQR 13–39.5] vs. 7 U [6–15], p < 0.001 and TRAP: 97 U [73–118.5] vs. 85 U [36–103], p = 0.035). Significant positive correlations were observed between agonist-induced platelet reactivity and BMI.ConclusionDespite the use of DAPT, a higher platelet reactivity was found in overweight and obese patients with CCS. If these patients will benefit from treatment with more potent platelet inhibitors, it needs to be evaluated in future clinical trials.

Abstract Background Platelet function testing in cats allows determination of clopidogrel effect. Plateletworks assesses aggregation based on decreasing platelet counts on hematology analyzers in response to agonists. It has not been validated for the IDEXX ProCyte Dx analyzer. Ideal time to perform analysis and the utility of other platelet parameters have not been fully assessed. Objectives To validate Plateletworks ADP on the ProCyte Dx, to investigate the utility of various platelet parameters using Plateletworks ADP, and determine the ideal time to perform analysis. Animals Twenty healthy cats recruited from the general population used for transference of reference intervals to a new analyzer, and 10 cats receiving clopidogrel to determine clopidogrel effect. Methods Plateletworks ADP using the ProCyte Dx and ADVIA 2120i analyzer was run simultaneously in both healthy cats and cats receiving clopidogrel, and CBC results at different timepoints were compared between analyzers. Results Aggregation was significantly different (P < .001) between analyzers. Cohen's kappa showed almost perfect agreement for determination of clopidogrel effect, and the area under the curve of the receiver operating characteristic was 1.0. Lower limits of the aggregation reference interval in healthy cats were 28.8% on the ProCyte Dx and 12.5% on the ADVIA 2120i. Coefficients of variation for platelet parameters were not different between analyzers. No significant changes in mean platelet volume, plateletcrit, large platelets, and mean platelet component were identified. No significant change in aggregation was observed within the first hour after phlebotomy. Conclusions and Clinical Importance Our study validated the Plateletworks ADP system on the ProCyte Dx analyzer. Samples may be analyzed up to 1 h after collection.

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.