Platelet Aggregation Values Research Articles

The potential clinical value of platelet aggregation in colorectal tumor progression

ObjectiveThe present study is to examine whether platelet aggregation function, platelet count and mean platelet volume are indicators that related to clinicopathological characteristics of colorectal cancer.MethodsA total of 546 patients with colorectal tumors and 118 healthy controls were enrolled, and patients with colorectal tumors were grouped according to malignancy, prognosis, recurrence and metastasis. The parameters of platelet aggregation function included max aggregation ratio, average aggregation ratio and max aggregation time were detected. 546 patients were induced by arachidonic acid, meanwhile, 415 of which were additionally induced by adenosine diphosphate. Of 118 healthy controls, 60 cases were induced by arachidonic acid and 58 cases were induced by adenosine diphosphate. We evaluated the intergroup significance of these indexes by receiver operating characteristic analysis.ResultsThe levels of max aggregation ratio, average aggregation ratio and platelet count were related to progression including cancerization, radical operation and recurrence and metastasis (P < 0.05). Notably, max aggregation ratio-arachidonic acid is the best indicator for predicting these three progressions with the areas under receiver operating characteristic curve of 0.685, 0.652, and 0.649, respectively.ConclusionCorrelations between max aggregation ratio, average aggregation ratio and colorectal tumor progression were observed with a certain clinical value.

Dynamics of hemostasis system parameters in assessing the risk of complications in the patients with acute myocardial infarction receiving antiplatelet therapy

Background. Current treatment of patients with myocardial infarction is based on the strategy of early invasive coronary intervention in combination with dual antiplatelet therapy - with acetylsalicylic acid and a P2Y12 blocker of platelet adenosine diphosphate receptors. In patients with thrombosis of the infarct-related artery, the phenomenon of “slow/ no reflow” (slowing of blood flow due to distal embolization of the artery), inhibitors of glycoprotein IIb/IIIa platelet receptors are administered as additional disaggregant therapy. In patients undergoing standard antiplatelet therapy in combination with glycoprotein IIb/IIIa inhibitors, there is a risk of hemorrhagic complications, therefore, monitoring of hemostasis parameters is necessary. Currently, there are no standard approaches to monitor the antiplatelet therapy.Objective. To study the dynamics of hemostatic system parameters in patients with acute myocardial infarction during antiplatelet therapy.Material and methods. We assessed platelet aggregation with 10 µmol of adenosine phosphate as an inducer in patients with ST-segment elevation myocardial infarction with different options of standard antiplatelet therapy in combination with GPIIb/IIIa inhibitors. Group 1 included 20 patients on dual antiplatelet therapy (clopidogrel 75 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor (tirofiban). Group 2 included 15 patients on dual antiplatelet therapy (ticagrelor 180 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor.Results. While on antiplatelet therapy the patients in both groups 1 and 2 demonstrated a decrease in platelet aggregation ability under the impact of adenosine phosphate, relative to the norm: 38 (21;43) % and 14 (11;15) %, respectively, the norm being 79 (73;84) % (p&lt;0.05). Meantime, no thrombotic events in the form of stent thrombosis were noted, which indicated antiplatelet therapy efficacy. In an intragroup comparison, the decrease in the platelet aggregation ability was most pronounced in group 2 (p&lt;0.05). By the 7th day of myocardial infarction, the platelet aggregation had continued to decrease to 26 (17;43) % in group 1, to 10 (7;11) % in group 2. The most pronounced effect of antiplatelet therapy was observed in group 2 (p&lt;0.05), which was manifested by a statistically significant decrease in platelet aggregation ability under the impact of 10 µmol of adenosine phosphate.Conclusions. While studying the hemostasis system changes over time in patients with myocardial infarction receiving antiplatelet therapy, we have found that making the platelet aggregation ability assessment with 10 µmol of adenosine phosphate as an inducer is possible to identify the effect of medications. However, further studies including larger patient groups are needed to determine the target values of platelet aggregation with 10 µmol of adenosine phosphate and assess the therapy efficacy.

The prognostic value of platelet aggregation in patients with sepsis.

This study aims to investigate the relevance of platelet aggregation markers, specifically arachidonic acid (AA) and adenosine diphosphate (ADP), in relation to the prognosis of sepsis patients. A cohort of 40 sepsis patients was included and stratified, based on their 28-day post-treatment prognosis, into two groups: a survival group (n = 31) and a severe sepsis group (n = 9. Then, their various clinical parameters, including patient demographics, platelet counts (PLT), inflammatory markers, and platelet aggregation rates (PAR) induced by AA and ADP between the two groups, were compared. Long-term health implications of sepsis were assessed using the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, and logistic regression analysis was conducted to evaluate the prognostic significance of PAR in sepsis patients. Patients with severe sepsis exhibited significantly elevated levels of procalcitonin (PCT), platelet adhesion rates, and PAR induced by ADP (P < 0.05), but having lower PLT (P < 0.05), compared to those in the survival group. Logistic regression analysis demonstrated that PAR induced by ADP was a protective factor in predicting prognosis in sepsis patients (P < 0.01). Activation of platelets in sepsis intensifies inflammatory response. Patients with sepsis whose ADP-induced PAR was < 60% displayed significant impairment in platelet aggregation function, and had higher mortality rate. Monitoring ADP-induced PAR is crucial for management of sepsis.

Identification of Molecular Markers Predicting the Outcome of Anti-thrombotic Therapy After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome and Atrial fibrillation: Evidence from a Meta-analysis and Experimental Study.

Acute coronary syndrome (ACS) and atrial fibrillation (AF) often coexist in clinical practice, and patients with these conditions often have a critical illness with high risk of both ischemia and bleeding. This study aims to report potential molecular markers for predicting the efficacy based on a meta-analysis of microarray data from the GEO database. In 40 patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) treated with PCI, P2RX1's effects on platelet aggregation, medication resistance, and predictive value were examined. Twenty up-regulated genes in peripheral blood samples of ACS and AF patients were down-regulated after PCI, while 7 down-regulated genes were up-regulated. ACS affected eight potential genes. P2RX1, one of the four LASSO analysis-retrieved disease characteristic genes, accurately predicted AF patients' thrombosis risk and PCI's anti-thrombotic impact. Therefore, P2RX1 may be a molecular marker to predict the effect of anti-thrombotic therapy in patients with ACS and AF after PCI.

Extracorporeal Detoxification Methods and Hemostasis System for Ovarian Cancer Patients. Clinical Case

Introduction. Malignant tumors dominate in the picture of disability and mortality worldwide. One of the most frequent and dangerous comorbid conditions is kidney injury. At the same time, the most unfavorable incidence of acute kidney injury is recorded in multiple myeloma, leukemia, lymphoma and kidney and/or liver cancer and malignant ovarian neoplasms. In this regard, of vital importance is the choice of tactics in the prevention of thrombosis and thromboembolic complications, as well as the individual approach to of the anticoagulant therapy regimen during renal replacement therapy sessions, depending on the underlying disease and the state of the hemostatic system. Aim. To evaluate the effect of calcium citrate veno-venous hemodiafi ltration sessions on the hemostatic system of a patient with progressive organ dysfunctions associated with malignant ovarian neoplasm. Materials and methods. The methodology involved literature review and a case study to assess the effect of veno-venous hemodiafi ltration on hemostasis. Results and discussion. The clinical case was assessed in terms of P-selectin (CD62), which characterizes platelet activation processes. It should be noted that in this patient, the expression of P-selectin increased with each session of renal replacement therapy, while the platelet aggregation values remained at the level of the lower thresholds, which indicates a low probability of coagulation initiation. However, due to aggressive regulation of ovarian cancer by the hemostatic system in the form of production of inflammatory mediators, microvesicles, tissue factor expression and endothelial activation, attention should be paid to the molecular aspects of platelet activation in renal replacement therapy with regional citrate coagulation. Conclusion. The widespread use of extracorporeal detoxification methods is an independent risk factor not only for bleeding events, but may potentially contribute to thrombosis and thromboembolic complications, which requires a further detailed study of molecular mechanisms of hemostasis regulation by tumor and clinical evaluation of various anticoagulation methods.

Platelet Aggregation in Apparently Healthy Elderly Populations: Reference Ranges and Influence of Hematology Parameters.

Reference intervals based on younger populations may not apply to elderly populations. The aim of the current study was to calculate reference ranges for platelet aggregation in apparently healthy Chinese elderly populations and analyze the impact of gender, age, and hematological parameters on platelet aggregation in vitro. A total of 138 males and 161 females were enrolled based on stringent inclusion and exclusion criteria. Platelet aggregation was measured with sodium citrate anticoagulation whole blood samples using a PL12 analyzer, triggered by adenosine-5'-diphosphate (ADP) and arachidonic acid (AA) agonists. Hematological parameters were measured using a Sysmex XE2100 instrument. In the total sample tested in this study, the platelet aggregation induced by AA and ADP was not dependent on age (p > 0.05) but gender. Platelet aggregation triggered by ADP and AA was more enhanced in females than males (p = 0.024 for AA, p = 0.036 for ADP). The recommended reference values of AA-induced platelet aggregation were 48.42% - 85.93% for males and 43.62% - 87.80% for females. The recommended reference values of ADP-induced platelet aggregation were 38.12% - 80.21% for males and 40.12% - 83.05% for females. Furthermore, for all agonists, a positive correlation was found between platelet aggregation and platelet count. The ADP-triggered aggregation showed a significant positive correlation with white blood cell (WBC) count and a negative correlation with red blood cell (RBC) count. Moreover, platelet aggregation showed no significant correlation with mean platelet volume or hemoglobin concentration. Combined and gender-specific reference ranges for platelet aggregation in healthy elderly populations were established in whole blood measured by a sequential platelet counting method.

Evaluation of cardiovascular risk biomarkers after moderate consumption of red wine and cachaça in a randomized crossover trial: The Wine and Cachaça Study (WICAS).

Moderate daily consumption of alcohol (MDCA) is associated with cardiovascular risk (CVR) reduction in observational studies. Some researches have suggested that this benefit may be associated not only with red wine consumption but also with other beverages. However, there are no clinical trials evaluating the possible CVR benefit of Brazilian spirit (cachaça) in humans. This is a prospective, randomized, crossover study including healthy individuals initially assigned to a MDCA of cachaça or red wine for a period of 4 weeks. After a one-week abstinence period, the type of drink was changed for another 4 weeks of intervention. The MDCA for both beverages was determined as a dose equivalent to 28g of ethanol per day for men and 14g for women. CVR biomarkers analyses were performed before and after each intervention to assess the serologic status of C-reactive protein, lipid profile, platelet aggregation and glycemic profile. This study is registered on the ISRCTN platform under number 15978506. Of the 42 subjects initially randomized, 2 refused to continue in the study. The median age was 44.3±10.3 years and 19 were male (47.5%). Adherence to the protocol was considered ideal with 100% regular use in both interventions and only 3 individuals in each intervention group reported alcohol abuse. There was no significant variation in anthropometric measurements during the study, except for weight gain (0.7kg) in the red wine group (p=0.005). The median of the delta of platelet aggregation for MDCA of cachaça was 1.2% (-1.1 to 5.3) and the median of the delta to the MDCA of wine was-1.6% (-4.5 to 2) (p=0.02). The other biomarkers didn't show any statistically significant variation. Moderate consumption of wine and cachaça was related to variation in laboratory biomarkers of CVR related to atherosclerosis. There was significant weight gain during the period of wine consumption and there was observed a difference between platelet aggregation values after both interventions.

Peculiarities of hemostasis in patients with COVID-19

Analysis of the dynamics of different stages of clot formation and its lysis in patients with different COVID-19 severity. We prospectively included 58 patients with COVID-19 (39 patients with moderate disease severity and 18 patients with severe disease) and 47 healthy volunteers as a control group. All participants underwent the assessment of flow-mediated dilation (FMD) of brachial artery, impedance aggregometry, rotational thromboelastometry and thrombodynamics. Von Willebrand factor antigen (vWF:Ag) quantification was also performed in patients with COVID-19. Measurements were repeated on the 3rd and 9th day of hospitalization. Compared to the control group, patients with COVID-19 showed reduced values of platelet aggregation and greater values of the clot growth rate, as well as its size and density. On the first day of hospitalization, we found no differences in the activity of plasma hemostasis and endogenous fibrinolysis between subgroups of patients. With the progression of the disease, the growth rate and size of the clot were higher in the severe subgroup, even despite higher doses of anticoagulants in this subgroup. An increase in platelet aggregation was noted during the progression of the disease, especially in the severe subgroup. There were no differences in the results of the FMD test by subgroups of patients. The vWF:Ag level was significantly higher in the severe subgroup. Thus, plasma hemostasis followed by secondary platelet activation correlates with the severity of COVID-19. Patients with moderate to severe coronavirus infection have predominantly local rather than generalized endothelial dysfunction.

The Role of Vitamin D and Platelet Aggregation in Patients with Hypertension

IntroductionPlatelet aggregation is seen in many inflammatory conditions and in the pathogenesis of chronic conditions like hypertension,atherosclerosis, diabetes mellitus. It is seen to be associated with complications of these diseases and also has a considerable influence on the morbidity and mortality. Vitamin D improves endothelial function and causes reduction of platelet aggregation. This study aims to determine the role of Vitamin D in platelet aggregation and its effects in reducing the morbidity and mortality in patients with hypertension.Materials and MethodsThe study was conducted at a tertiary healthcare centre in 50 primary hypertensives. All subjects completed physical and cardiovascular system examination. Blood pressure recordings were done. A blood sample was taken from each patient. Platelet aggregation was estimated using chronologaggregometer after extracting platelet rich plasma using principle of light transmission. ADP and epinephrine were added to PRP to induce platelet aggregation. Serum Vitamin D levels were also measured. The values of platelet aggregation were correlated with serum Vitamin D levels in each subject.ResultsPlatelet aggregation and Vitamin D levels were correlated and a negative correlation was found. Correlation coefficient of platelet aggregation to ADP with Vitamin D was ‐0.992 (p value&lt;0.0001) and of platelet aggregation to epinephrine with Vitamin D was ‐0.838 (p value&lt;0.0001).ConclusionThe study determines that platelet aggregation is one of the physiological events that occurs in hypertension and may be one of the causative factors of complications like cerebrovascular accidents, ischemic heart diseases etc. Cases with lower serum Vitamin D levels showed increased platelet aggregation showing an inversely proportional relationship between platelet aggregation and serum Vitamin D levels. Hence, it can be concluded that supplementation of Vitamin D can be considered in patients with hypertension as a primary prophylactic measure for reducing thrombotic complications of hypertension and helps improve the morbidity and mortality.

Is there a Role of Anti‐platelet Aggregation Agents in the Management of Primary Hypertension: An In‐Vivo Study

INTRODUCTIONHypertension is a leading identifiable and reversible risk factor for myocardial infarction, heart failure, atrial fibrillation, aortic dissection, peripheral arterial disease, stroke, kidney failure, etc with thrombus being the culprit lesion. South Asian ethnicity predisposes to higher mortality and morbidity from cardiovascular disease than other ethnic groups and is estimated to cause 7.5 million deaths, which accounts for 57 million disability‐adjusted life years (DALYs).Hypertension causes changes in platelets (shape, size, expression of P‐selectin, and sensitivity to catecholamines,) However, the data on platelet aggregation is sparse, inconclusive, and has shown contradictory results in Asian Indians. Therefore, this study is designed to study the platelet aggregation in Indian hypertensives and to investigate if platelet aggregation is determined by the level of blood pressure.MATERIALS AND METHODSThe study was conducted at the tertiary health center in 50 primary hypertensives &amp; compared with age &amp; sex‐matched healthy controls. After ethics approval from IRB, an informed and written consent was taken. All subjects completed a physical and cardiovascular system examination. Blood pressure recordings were done as per JNC‐VIII Guidelines and were further divided into sub‐groups as per the JNC‐VIII classification. Platelet rich plasma was used to estimate aggregation using a Chronolog aggregometer based on the principle of light transmission. ADP (5 µM) &amp; Epinephrine (2µM) were added to PRP to induce platelet aggregation. The normal value of platelet aggregation was compared between study subjects and controls using Independent t test and Mann‐Whitney Test.RESULTSAfter comparing platelet aggregation to ADP and epinephrine in primary hypertensives and healthy controls, 28 cases had stage I and 22 had stage II hypertension. The mean platelet aggregation to ADP in normotensives and primary hypertensives was 31.32±6.64 and 73±10.07, respectively (p value&lt;0.0001). Similarly, the mean platelet aggregation to Epinephrine in normotensives and primary hypertensives was 24.82±5.51and 50.94±12.19, respectively (p value&lt;0.0001). (Fig 1) Furthermore, platelet aggregability was found to be significantly increased in primary hypertensives as compared to controls. Moreover, it was further raised in stage II hypertensives in comparison to stage I hypertensives.(Fig 2)CONCLUSIONSThis study is the largest prospective study conducted on plasma from hypertensives and implicates platelet aggregation as a the causative factor leading to cerebrovascular accidents, ischemic heart diseases in primary hypertensives. Hence, any anti‐hypertensive drug which confers additional anti‐platelet aggregation properties may benefit in the management of hypertension especially in the Indian population. However, further larger studies are recommended to verify the same.

Microvascular rarefaction in patients with cerebrovascular events.

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n=13 ischemic, n=1 ischemic with hemorrhagic transformation and n=2 hemorrhagic stroke) or transitory ischemic attacks (n=5) within 24h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717μm/mm2, p=0.001 and 5263 vs 6550μm/mm2, p=0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717μm/mm2, p<0.001 and 5263 vs. 6550μm/mm2, p=0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r=-0.843, p<0.001), in patients with ischemic strokes (r=-0.82, p=0.001) as well as in healthy volunteers (r=-0.845, p<0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.

Hemocompatibility And Cytotoxicity Of Small-Diameter Bioabsorbable Tissue-Engineered Vascular Grafts Depending On Anti-Thrombogenic And Antimicrobial Coating

Anti-thrombogenic and antimicrobial coatings of polymer grafts constitute a promising approach to preventing infection and thrombosis of vascular grafts. The objective was to study the hemocompatibility and cytotoxicity of PHBV/PCL grafts with iloprost and amphiphilic coating. Material and Methods — Polymer matrices were manufactured by electrospinning a mixture of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) polymers. Several matrices were modified by complexation between polyvinylpyrrolidone (PVP) and cationic amphiphile and/or iloprost. The amphiphile was covalently cross-linked to the surface of other PHBV/PCL matrices. Unmodified PHBV/PCL matrices were used as the control group. Hemocompatibility and cytotoxicity of scaffolds before and after the modification were evaluated. Results — The hemocompatibility assessment revealed that hemolysis degree did not exceed normal values in all types of matrices. The PHBV/PCL/PVP matrices had increased platelet aggregation on the surface of the grafts. Subsequent addition of iloprost and amphiphile resulted in a sevenfold reduction of platelet aggregation. In PHBV/PCL/PVP matrices, the degree of platelet adhesion increased without changing the platelet deformation index values. Iloprost and amphiphilic coating of PHBV/PCL/PVP matrices diminished the number of adhered platelets and platelet deformation index by 1.5 times. The amphiphile, covalently cross-linked to PHBV/PCL matrices, caused a negative effect on the platelet adhesion, aggregation, and deformation index values. Evaluation of cytotoxicity of PHBV/PCL/PVP matrices, coated with iloprost and/or cationic amphiphile, demonstrated a slight decline in the rates of cell growth and proliferation after three days. Moreover, after three days, cell deaths and a sharp drop in the cell index values were noted in PHBV/PCL matrices with covalently cross-linked amphiphile. Conclusion — Iloprost and amphiphilic coating of PHBV/PCL grafts has increased their hemocompatibility. Also, there were no signs of cytotoxicity while using the complexation technique. However, covalently cross-linked amphiphile caused an increase in the cytotoxicity of matrices, which may have been indicative of the negative effect observed in this type of surface modification.

Potensi Ekstrak Etanol Daun Sirih (Piper Betle L.) Sebagai Pengganti ADP (Adenosine Diphosphate) Pada Pemeriksaan Agregasi Trombosit

Adenosine diphosphate (ADP) reagent is often used in the examination of platelet aggregation, yet has limitations in terms of price and availability. Natural source namely betel leaf (Piper betle L.) are believed to be used as a substitute for ADP because betel leaf have the characteristics of styptic (to resist bleeding), vulnerary (to heal skin wounds), and anti-inflammatory (to preserve inflammation) (Moeljanto &amp; Mulyono, 2003). The aim of this study was to determine the potential of betel leaf on the examination of platelet aggregation. The method used in this research included the betel leaf extraction using ethanol as solvent with an evaporator. The extract obtained was used as a substitute for the ADP reagent in platelet examination in the form of determining the percentage of platelet aggregation in 16 human blood samples, with a population of students at the University of Muhammadiyah Semarang. The final results showed that the addition of betel leaf extraction to the 16 blood samples examined gave an average value of platelet aggregation percentage which was higher (65%) than the mean value of platelet aggregation using ADP reagent mixing (57%). Both results fall within the normal value range, namely 50-70%. It can be concluded that betel leaf extract has the potential to be used as a replacement reagent for ADP in the process of examining platelets, especially in determining the percentage value of platelet aggregation.

Analysis of Low Dose Aspirin on Platelet Aggregation Percentage in High-Risk Pregnancy Hypertension

Objective: Low dose aspirin (LDA) is one of platelet aggregation agents in high-risk pregnancy that is believed to prevent complication by inhibiting thromboxane A2 as a strong vasoconstrictor in platelet. It can inhibit platelet aggregation involved in pathophysiology of pregnancy hypertension. The aim of this study is to analyse the effect of LDA on platelet aggregation in pregnant patient with high-risk hypertension. Material and methods: A prospective observational method was conducted in this study. It was approved by the Ethics Committee of Haji Teaching Hospital Surabaya. Data was collected from July to September 2018 involving 18 patients divided into three groups who have age of 35-39 years old in the majority. The range of gestational age in this study was 19-37 weeks. Platelet aggregations on plasma were measured before and 14 – 30 days after LDA use. The collected data were statistically analyzed by using a paired t-test. Results: Platelet aggregation percentage using collagen agonists was an increase of 0.8% (p > 0.05) in the old patient group and followed by 6% (p > 0.05) in the group of patients who did not get LDA. Whereas in the group of new patients showed a decrease of 6% (p > 0.05). While ADP agonists showed that the group of new patients decreased by 17% (p > 0.05), followed by the group of patients who did not use LDA of 9% (p > 0.05) and the old patient group was 4% (p > 0.05). Conclusions: Low-dose aspirin use did not affect a decrease in platelet aggregation values.

Use of increased concentrations of adenosinediphosphate for high residual platelet reactivity in patients with coronary heart disease

Detection of a tendency to increased thrombosis in patients with coronary heart disease (CHD) is of important prognostic value in the selection of drugs aimed at achieving a persistent antithrombotic effect. The aim of the study was to evaluate the use of elevated ADP inducer concentrations to improve the accuracy of ADP-induced platelet aggregation in patients with coronary heart disease. Material and method. Material and method. We studied 48 patients with CHD who were on continuous double antiplatelet therapy for 6 months (aspirin 75mg and clopidogrel 75mg per day). The aggregation activity of the platelet suspension was studied using the Born method G. in the modification of Gabbasov Z. A. Platelet activity was evaluated by the degree of aggregation of platelet-rich plasma along the light transmission curve under the influence of the inducer adenosine diphosphate (ADP) at a concentration of 2 mmol/l and by its own patented method against the background of additional ADP application. Results. In patients, platelet aggregation decreased to 5-35% (p&lt;0.005) compared to the standard values, which are 50-60%. The values of platelet aggregation with the additional introduction of the inducer of aggregation ADP in a ratio of 2:1 to 2 µmol/l for 1, 2, 3, and 4-minute registration of platelet aggregation, resulted in increased aggregation from 55% to 75% (p&lt;0.001), indicating high residual platelet reactivity on the background of double antiplatelet therapy. Correlations of the degree of aggregation for elevated ADP concentrations with multivessel arterial lesion and dyslipidemia were also found, r=0.86 and r=0.92, respectively. Conclusion. The use of elevated concentrations of adenosine diphosphate in platelet aggregation in patients with ischemic heart disease increases the accuracy of assessing ADP-induced platelet aggregation against the background of dual antiplatelet therapy and contributes to the detection of high residual platelet reactivity.

Impact of renin angiotensin system inhibitors on homocysteine levels and platelets reactivity in patients on dual antiplatelet therapy

Background and aimsDual antiplatelet therapy (DAPT) and Renin-angiotensin system inhibitors (RASi) represent the cornerstone in the treatment of patients undergoing percutaneous coronary interventions (PCI), mainly after an acute ischemic event. However, high-on treatment residual platelet reactivity (HRPR), is not infrequent despite optimal medical treatment. Homocysteine (Hcy) is a metabolite of methionine catabolism linked to atherothrombosis. Recently, a potential crosstalk between RAS and Hcy has been suggested, potentially favouring platelet aggregation and cardiovascular disease.Therefore, we aimed to investigate the impact of RASi on Hcy levels and platelet aggregation in patients on DAPT after PCI. Methods and resultsPatients undergoing PCI on DAPT with ASA plus an ADP-antagonist (clopidogrel, ticagrelor or prasugrel), were included. RASi comprised angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Aggregation tests were performed by Multiple Electrode Aggregometry. We included 1210 patients, of whom 862 (71.2%) were on treatment with RASi. Overall, DAPT composition was ASA+clopidogrel in 566 (46.8%) patients, ASA+ticagrelor in 428 (35.4%) and ASA+prasugrel in 216 (17.9%). Median values of Hcy were higher in RASi patients (p = 0.006), who displayed a higher percentage of Hcy above the median value (52.4% vs. 44.8%, p = 0.019, adjustedOR [95%CI] = 1.40 [1.04–1.88], p = 0.027). No differences in HRPR rate were found according to RASi use for ASPI test (3.6% vs. 3.3%, p = 0.88) and ADP test (25.6% vs. 24.3%,p = 0.62; adjustedOR [95%CI] = 1.23 [0.89–1.70], p = 0.220) and according to ADP-antagonist type. A direct linear relationship was observed between platelet reactivity and Hcy in both patients receiving RASi and untreated ones, with higher values of platelet aggregation being observed in patients with Hcy above the median, independently from RASi administration and DAPT strategy. ConclusionIn patients on DAPT after PCI, RASi treatment did not emerge as an independent predictor of HRPR. However, the levels of Hcy were significantly elevated in patients on RASi and related to higher values of platelet reactivity, independently from the DAPT strategy.

ADP-induced platelet aggregation in patients with acute coronary syndrome treated with prasugrel or ticagrelor. Results of the ISAR REACT 5 platelet aggregation substudy

Abstract Introduction The recently published randomized multicenter open label ISAR REACT 5 trial showed that prasugrel was superior to ticagrelor with respect to the composite primary end point of death, myocardial infarction, or stroke at one year after randomization in patients with acute coronary syndrome with planned invasive evaluation. The reasons for this finding are speculative. Purpose The aim of this prespecified platelet aggregation substudy was to assess platelet aggregation induced by adenosine-diphosphate (ADP) in patients who received prasugrel or ticagrelor treatment and underwent PCI. Methods We assessed all patients who underwent PCI and who had valid ADP-induced platelet aggregation values at hospital admission and at 2–24 hours after administration of prasugrel or ticagrelor loading dose followed by maintenance dose. ADP-induced platelet aggregation values were measured using the Mulitplate Analyzer®. Patients were recruited in the German Heart Center, Munich, Germany or in Klinikum rechts der Isar, Munich, Germany, Technical University of Munich. Results A total of 608 patients were analyzed. Patients in the prasugrel group were slightly but significantly older than patients in the ticagrelor group (66,5 years versus 64,6 years, P=0,048). The remaining baseline characteristics did not significantly differ between the two treatment groups. ADP-induced platelet aggregation (median [IQR]) at baseline did not differ between prasgurel- and ticagrelor treated patients (809 [556; 1057] AU x min versus 797 [534–1095] AU x min. At 2–24 hours after study drug administration ADP-induced platelet aggregation was significantly lower in patients who had received prasugrel in comparison to ticagrelor (105 [57–176] AU x min versus 138 [77–207] AU x min (Figure 1). Conclusion ADP-induced platelet aggregation was significantly lower in patients who received prasugrel in comparison to patients who received ticagrelor, which could have influenced patients' outcome in the ISAR-REACT 5 trial. Figure 1 Funding Acknowledgement Type of funding source: None

Thrombocyte aggregation activity in the conditions of intensive light deprivation

The aim of the research was to study the effect of photoperiodism disturbances on platelet aggregation activity. Material and methods. The experiment was conducted in two stages in 5 groups of male rats: the control group and four experimental groups. At the first stage, the animals were exposed to 24 h/day continuous light (24L:0D) for 10 and 21 days. In the second stage, animals after 10 and 21 days of round-the-clock lighting were returned to natural lighting for a period of 21 days to study the reversibility of changes. Animals were withdrawn from the experiment by intramuscular injection based on body weight of drugs for anesthesia (telazol, xylanite). Blood sampling was performed by puncture of the right heart. The functional activity of platelets was determined no later than 3 hours after the collection of blood. Results and discussion. The results of the experiment indicate a direct effect of light desynchronosis on the increase in platelet aggregation ability, while it was noted that the degree of increase in aggregation activity and reversibility of changes directly depend on the duration of round-the-clock lighting. So, a 10-day stay of animals in conditions of abnormal lighting leads to an increase in aggregation indices, which remain at a high level even when animals return to normal conditions. In animals that were under round-the-clock illumination for 21 days, a more pronounced increase in platelet aggregation values relative to animals on day 10 was noted. In this regard, it can be argued that circadian rhythm disturbances provoke the development of microvasculature disorders.

Optimal strategy of switching from clopidogrel to ticagrelor in Chinese acute coronary syndrome patients with complicated coronary artery disease: the switching from clopidogrel to ticagrelor (SHIFT-CACS) study.

The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI). From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint. The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events. The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel. ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

Platelet reactivity patterns in patients treated with dual antiplatelet therapy.

AimThe aim of the present study was to investigate the patterns of platelet reactivity and discriminators of therapeutic response to dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel in patients with acute coronary syndrome (ACS).DesignIn this multicentre prospective observational study, 492 patients with ACS were enrolled. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) or arachidonic acid (AA) as agonists in the maintenance phase of treatment with prasugrel or ticagrelor.ResultsAge emerged as the strongest variable influencing aspirin response status: The mean AA‐induced platelet aggregation in patients <49 years of age was 49% higher than in those >49 years (13.1 U vs 8.8 U; P = 0.011). The second strongest discriminator of aspirin response was sex: Male patients had a 40% higher AA‐induced platelet aggregation values than female patients (9.5 U vs 6.8 U; P = 0.026). Platelet count emerged as the only variable influencing ADP antagonists response status showing that patients with platelet count >320 g/L displayed higher ADP‐induced platelet aggregation. About 12% of patients had high on‐treatment platelet reactivity (HTPR) to aspirin, 3% and 4% a HTPR to prasugrel and ticagrelor, respectively, and only 2% displayed HTPR to dual antiplatelet therapy.ConclusionWhen potent platelet inhibitors as prasugrel and ticagrelor are administered with aspirin, HTPR to DAPT plays only a marginal role.