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BACKGROUND: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. METHODS: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). RESULTS: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. CONCLUSION: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Masculino , Feminino , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Idoso , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Terapia Antiplaquetária Dupla/métodos , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Trombose/etiologia , Trombose/prevenção & controle , Plaquetas/efeitos dos fármacos , Trombectomia/métodosRESUMO
Background: Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses. Objectives: Our aim was to compare well-used platelet reactivity assays. Methods: Blood and platelet-rich plasma obtained from the Framingham Heart Study (N = 3429) were assayed using a range of agonists in 5 platelet assays: light transmission aggregometry, Optimul aggregometry, Multiplate impedance aggregometry (Roche Diagnostics), Total Thrombus-Formation Analysis System, and flow cytometry. Using linear mixed-effect models, we determined the contribution of preanalytical and technical factors that modulated platelet reactivity traits. Results: A strong intra-assay correlation of platelet traits was seen in all assays, particularly Multiplate velocity (r = 0.740; ristocetin vs arachidonic acid). In contrast, only moderate interassay correlations were observed (r = 0.375; adenosine diphosphate Optimul Emax vs light transmission aggregometry large area under the curve). As expected, antiplatelet drugs strongly reduced platelet responses, with aspirin use primarily targeting arachidonic acid-induced aggregation, and explained substantial variance (ß = -1.735; P = 4.59 × 10-780; variance proportion = 46.2%) and P2Y12 antagonists blocking adenosine diphosphate responses (ß = -1.612; P = 6.75 × 10-27; variance proportion = 2.1%). Notably, female sex and older age were associated with enhanced platelet reactivity. Fasting status and deviations from standard venipuncture practices did not alter platelet reactivity significantly. Finally, the agonist batch, phlebotomist, and assay technician (more so for assays that require additional sample manipulation) had a moderate to large effect on measured platelet reactivity. Conclusion: Caution must be exercised when extrapolating findings between assays, and the use of standard ranges must be medication-specific and sex-specific at a minimum. Researchers should also consider preanalytical and technical variables when designing experiments and interpreting platelet reactivity measures.
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Lipid emulsions are essential components of parenteral nutrition solutions that provide energy and essential fatty acids. The complexity of the formulations of lipid emulsions may lead to adverse outcomes such as platelet reactivity and changes in platelet aggregation and related coagulation. Platelets are responsible for haemostasis; they activate and demonstrate morphological changes upon extracellular factors to maintain blood fluidity and vascular integrity. Although parenteral nutrition lipid emulsions are generally found safe with regard to modulation of platelet activity, studies are still accumulating. Thus, this review aims to investigate platelet-related changes by parenteral nutrition lipid emulsions in human studies. Studies have pointed out patients at risk of bleeding and increased platelet aggregation responses due to the administration of lipid emulsions. Lipid emulsions may further benefit patients at high risk of thrombosis due to anti-thrombotic effects and should be cautiously used in patients with thrombocytopenia. The reported platelet-related changes might be associated with the fatty acid change in the plasma membranes of platelets following changes in platelet synthesis and plasma levels of eicosanoids. In conclusion, studies investigating platelets and parenteral nutrition should be supported to minimize the adverse effects and to benefit from the potential protective effects of parenteral nutrition lipid emulsions.
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Ácidos Graxos , Nutrição Parenteral , Humanos , Emulsões , Nutrição Parenteral/efeitos adversos , EicosanoidesRESUMO
BACKGROUND: Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). Multiple factors may concur to explain this, including increased amount of highly reactive immature platelets. OBJECTIVES: To investigate the association between immature platelets and reactivity determined with multicolour flow cytometry using the SYTO-13 dye in STEMI patients. METHODS: We conducted an observational study of 59 patients with acute STEMI. Blood samples were obtained within 24 h after admission and after loading doses of dual antiplatelet therapy. For comparison, samples were obtained from 50 healthy individuals. Immature platelets and platelet reactivity were investigated using multicolour flow cytometry including the SYTO-13 dye that binds to platelet RNA and thus provides a method for subdividing platelets into immature and mature platelets. Additionally, we assessed platelet aggregation, serum-thromboxane B2 levels and standard immature platelet markers. RESULTS: Immature platelets were more reactive than mature platelets in both STEMI patients and healthy individuals (p-values < 0.05). STEMI patients had lower platelet aggregation and thromboxane B2 levels than healthy individuals. We found a positive association between automatically determined immature platelet markers and CD63 expression on activated platelets (Spearman's rho: 0.27 to 0.58, p-values < 0.05). CONCLUSIONS: Our study shows that immature platelets identified with a multicolour flow cytometric method using the SYTO-13 dye are more reactive than mature platelets in patients with acute STEMI and in healthy individuals. The presence of immature platelets may be important for the overall platelet reactivity, which may have implications for the effect of antiplatelet therapy.
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Plaquetas , Citometria de Fluxo , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Plaquetas/metabolismo , Citometria de Fluxo/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacosRESUMO
In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.
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Hemostasia , Humanos , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/normas , Hemorragia/terapia , Hemorragia/sangue , Hemorragia/diagnóstico , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/terapia , Transtornos Hemorrágicos/sangue , Fenótipo , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Terminologia como AssuntoRESUMO
Optical aggregometry by 96-well plate assay, the microplate method, is a fast, efficient, and readily available method for measuring the pharmacological effects of antiplatelet drugs. Even though recent years have witnessed growing interest in adopting the microplate method for widespread use, it remains in the shadow of the standard light transmission aggregometry (LTA). Regardless of the method used, the results of platelet aggregation depend on a variety of factors and often vary among laboratories worldwide. While several methodological papers have examined the microplate method, no standards have been established, most likely because the approach is not used as a diagnostic tool. Currently, the microplate method is recommended by researchers to be used in conjunction with LTA or as an adjunct to LTA. This raises the question of whether an optimal protocol exists for microplate aggregometry, and what are the key considerations in a good experimental protocol for obtaining reliable results? This article attempts to address these questions by summarizing the knowledge accumulated in this field over the last three decades.
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Agregação Plaquetária , Testes de Função Plaquetária , Testes de Função Plaquetária/métodos , Inibidores da Agregação Plaquetária/farmacologia , Padrões de Referência , PlaquetasRESUMO
The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.
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Coagulação Sanguínea , Inibidor de Coagulação do Lúpus , Humanos , Testes de Coagulação Sanguínea/métodos , Tempo de Protrombina , Tempo de Tromboplastina Parcial , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The platelet-driven contraction or retraction of blood clots has been utilized to obtain blood serum for laboratory studies, but now, in vitro clot contraction assays are used in research laboratories and clinics to assess platelet functionality. The static final extent of clot contraction measured using a clot size or expelled serum volume can be supplemented substantially with a dynamic analysis. OBJECTIVES: To provide a step-by-step protocol for a relatively simple and affordable new automated methodology to follow the kinetics of blood clot contraction, which allows for simultaneous measurements of various samples at a time and requires only a fluorescence plate reader. METHODS: The kinetics of clot contraction in whole blood was assessed by continuously detecting the fluorescence intensity of fluorescein isothiocyanate-albumin added to a blood sample before clotting and expelled into the serum during clot shrinkage. RESULTS: The clots are formed and fluorescence is measured in the wells of a black multiwell plate using a standard plate fluorescent reader. The specificity of this technique for clot contraction has been demonstrated by the strong inhibitory effects of blebbistatin, latrunculin A, and abciximab. To validate the new technique, increased fluorescence intensity in the contracting clots was measured in parallel with a visual decrease in clot size performed with the same blood samples. CONCLUSION: The resulting clot contraction dynamics based on the expulsion of fluorescein isothiocyanate-albumin can be quantified using a number of kinetic parameters as well as a phase kinetics analysis. The advantages and drawbacks of the new technique are discussed.
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Coagulação Sanguínea , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Cinética , Coagulação Sanguínea/efeitos dos fármacos , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Reprodutibilidade dos Testes , Testes de Coagulação Sanguínea/métodos , Retração do Coágulo , Fatores de Tempo , Trombose/sangue , Albumina SéricaRESUMO
BACKGROUND: Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often have altered blood cell counts, which are associated with venous thromboembolism (VTE) development. The high thrombotic risk in patients with PDAC may be partially caused by procoagulant blood cells. OBJECTIVES: The aim of this study was to compare blood cell-dependent coagulation between patients with PDAC (n = 18) and healthy controls matched for age and sex (n = 18). METHODS: Thrombin generation (TG) was measured in whole blood (WB) and plasma. The capacity of platelets to release granules (PGRCs) was measured in WB. We explored the occurrence of thromboembolic events in patients with PDAC during a 6-month follow-up. RESULTS: Patients showed an increased endogenous thrombin potential in WB compared with controls. This difference was not observed in plasma, indicating a procoagulant effect of blood cells. Both in WB and plasma, the lag time was prolonged in patients compared with controls. Patients had hyperresponsive platelets, with a shorter time to peak granule release. Of the 18 patients with PDAC, 4 developed a venous thromboembolism (22%) and 1 developed an arterial thrombosis (6%). A shorter lag time in WB, but not in plasma, and an increased PGRC were associated with thromboembolic events. CONCLUSION: Patients with PDAC have an increased and delayed WB TG coagulation profile compared with controls. A shorter lag time in WB TG and increased PGRC are associated with the incidence of thromboembolic events. Platelets appear to be key players in thrombosis development. Measuring hemostasis in WB could improve thrombosis risk estimation in patients with PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Trombose , Tromboembolia Venosa , Humanos , Trombina , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/complicações , Plaquetas , Trombose/etiologia , Neoplasias Pancreáticas/complicaçõesRESUMO
Background: In hemophilia and von Willebrand disease, the degree of alteration of laboratory assays correlates with bleeding manifestations. Few studies have assessed the predictive value for bleeding of laboratory assays in patients with inherited platelet function disorders (IPFDs). Objectives: To assess whether there is an association between platelet function assay results and bleeding history, as evaluated by the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT). Methods: Centers participating in the international ISTH-BAT validation study were asked to provide results of the diagnostic assays employed for the patients they enrolled, and the association with the individual patients' bleeding score (BS) was assessed. Results: Sixty-eight patients with 14 different IPFDs were included. Maximal amplitude of platelet aggregation was significantly lower in patients with a pathologic BS and correlated inversely with the BS, a finding largely driven by the subgroup of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency; after their exclusion, TRAP-induced aggregation remained significantly lower in patients with a pathologic BS. Bleeding time was significantly more prolonged in patients with a high BS than in those with a normal BS (27.1 ± 6.2 minutes vs 15.1 ± 10.6 minutes; P < .01). Reduced α-granule content was significantly more common among patients with a pathologic BS than among those with a normal BS (80% vs 20%; P < .05). Receiver operating characteristic curve analysis revealed a significant discriminative ability of all the aforementioned tests for pathologic BS (P < .001), also after exclusion of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency. Conclusion: This study shows that altered platelet laboratory assay results are associated with an abnormal ISTH-BAT BS in IPFD.
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BACKGROUND: Platelet (PLT) product transfusion is a life-saving therapy for actively bleeding patients. There is an urgent need to maintain PLT function and extend shelf life to improve outcomes in these patients. Cold-stored PLT (CS-PLT) maintain hemostatic potential better than room temperature-stored PLT (RT-PLT). However, whether function in long-term CS-PLT is maintained under physiological flow regimes and/or determined by cold-induced metabolic changes is unknown. OBJECTIVES: This study aimed to (i) compare the function of RT-PLT and CS-PLT under physiological flow conditions, (ii) determine whether CS-PLT maintain function after 3 weeks of storage, and (iii) identify metabolic pathways associated with the CS-PLT lesion. METHODS: We performed phenotypic and functional assessments of RT- and CS-PLT (22 °C and 4 °C storage, respectively; N = 10 unique donors) at storage days 0, 5, and/or 21 via metabolomics, flow cytometry, aggregation, thrombin generation, viscoelastic testing, and a microfluidic assay to measure primary hemostatic function. RESULTS: Day 21 4 °C PLT formed an occlusive thrombus under arterial shear at a similar rate to day 5 22 °C PLT. Day 21 4 °C PLTs had enhanced thrombin generation capacity compared with day 0 PLT and maintained functionality comparable to day RT-PLT across all assays performed. Key metrics from microfluidic assessment, flow cytometry, thrombin generation, and aggregation were associated with 4 °C storage, and metabolites involved in taurine and purine metabolism significantly correlated with these metrics. Taurine supplementation of PLT during storage improved hemostatic function under flow. CONCLUSION: CS-PLT stored for 3 weeks maintain hemostatic activity, and storage-induced phenotype and function are associated with taurine and purine metabolism.
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Hemostáticos , Humanos , Trombina/metabolismo , Preservação de Sangue , Plaquetas/metabolismo , Purinas/metabolismoRESUMO
INTRODUCTION: Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin-induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L-PRP). Previously, we developed a strategy for diagnostic LTA assessment of L-PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L-PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression-derived 95% confidence intervals, determined for diluted control L-PRP (C-L-PRP). METHODS: To further evaluate the L-PRP LTA strategy, we evaluated findings for a subsequent patient cohort. RESULTS: Between 2008 and 2021, the L-PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109 /L) for blood and L-PRP were: 105 [13-282; 89% with thrombocytopenia] and 164 [17-249], respectively. Patient-L-PRP had more abnormal MA findings than simultaneously tested C-L-PRP (p-values <0.001). Among patients with accessible electronic medical records (n = 181), L-PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L-PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L-PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3-related thrombocytopenia, and acquired PFD. CONCLUSION: Diagnostic LTA with L-PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative.
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Transtornos Plaquetários , Plasma Rico em Plaquetas , Trombocitopenia , Doenças de von Willebrand , Humanos , Contagem de Plaquetas , Agregação Plaquetária , Testes de Função Plaquetária , Plaquetas/patologia , Doenças de von Willebrand/diagnóstico , Trombocitopenia/diagnóstico , Trombocitopenia/patologia , Transtornos Plaquetários/diagnósticoRESUMO
Background: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at a risk of developing cardiovascular disease. Antiplatelet therapy not only prevents cardiovascular disease in these patients, but may also lower the risk of progression into advanced stages of fibrosis. However, patients with MASLD-associated cirrhosis often have complex changes in the hemostatic system and have been excluded from randomized trials. Objectives: The aim of this study was to assess the potency of antiplatelet drugs in these patients with MASLD-associated cirrhosis. Methods: We included patients with MASLD-associated cirrhosis (n = 19), patients with type 2 diabetes (DM2) and steatosis (n = 22), patients with steatosis only (n = 15), and healthy controls (n = 20). We measured basal platelet aggregation and activation using light transmission aggregometry and flow cytometry. We subsequently measured platelet aggregation and activation after in vitro addition of aspirin, cangrelor, and ticagrelor and compared the antiplatelet response in patients and healthy controls. Results: Rates of aspirin resistance as measured by light transmission aggregometry were similar between patients with MASLD-associated cirrhosis and healthy controls (21% vs 16%), but were significantly higher in patients with DM2 and steatosis (50% [P = .02] vs controls) and patients with steatosis only (53% [P = .05] vs controls). In patients with DM2 and steatosis, but not with MASLD-associated cirrhosis, the potency of cangrelor was significantly lower than that in healthy controls (P = .028). Conclusion: The in vitro potency of aspirin, cangrelor, and ticagrelor in samples of patients with MASLD-associated cirrhosis is similar to that of healthy controls. In contrast, the potency of commonly used antiplatelet drugs may be altered in patients with DM2 and steatosis and in patients with steatosis only.
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Background: Flow cytometry is an important technique for understanding multiple aspects of blood platelet biology. Despite the widespread use of the platform for assessing platelet function, the optimization and careful consideration of preanalytical conditions, sample processing techniques, and data analysis strategies should be regularly assessed. When set up and designed with optimal conditions, it can ensure the acquisition of robust and reproducible flow cytometry data. However, these parameters are rarely described despite their importance. Objectives: We aimed to characterize the effects of several preanalytical variables on the analysis of blood platelets by multiparameter fluorescent flow cytometry. Methods: We assessed anticoagulant choice, sample material, sample processing, and storage times on 4 distinct and commonly used markers of platelet activation, including fibrinogen binding, expression of CD62P and CD42b, and phosphatidylserine exposure. Results: The use of suboptimal conditions led to increases in basal platelet activity and reduced sensitivities to stimulation; however, the use of optimal conditions protected the platelets from artifactual stimulation and preserved basal activity and sensitivity to activation. Conclusion: The optimal preanalytical conditions identified here for the measurement of platelet phenotype by flow cytometry suggest a framework for future development of multiparameter platelet assays for high-quality data sets and advanced analysis.
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PURPOSE: To assess the antiplatelet effect of cilostazol clinically, we compared the effects of cilostazol in combination with clopidogrel on various platelet function tests. METHODS: We recruited patients with ischemic stroke at high risk of recurrence who were treated with clopidogrel alone within 180 days after stroke onset. Subjects underwent baseline platelet function tests, and were then randomly assigned to receive dual antiplatelet therapy (DAPT) comprising clopidogrel and cilostazol or clopidogrel monotherapy (SAPT). After 6 months, platelet function was measured again and compared to that at baseline in each group, and the rate of change was compared between groups. RESULTS: Thirty-four patients were enrolled, but 4 patients were excluded for various reasons. In total, 30 subjects (13 in DAPT and 17 in SAPT group) were analyzed. Adenosine diphosphate- and collagen-induced aggregation, VerifyNow P2Y12 reaction units, vasodilator-stimulated phosphoprotein (platelet reactivity index: PRI) and plasma p-selectin concentration were significantly lower (P = 0.004, 0.042, 0.049, 0.003 and 0.006 respectively), while VerifyNow % inhibition was significantly higher at 6 months compared to baseline (P = 0.003) in the DAPT group only. Comparison of the rate of change in each parameter from baseline to 6 months showed that while PRI decreased at a greater rate (P = 0.012), VerifyNow % inhibition increased at a greater rate (P = 0.003) in the DAPT group than the SAPT group. CONCLUSIONS: The inhibitory effects of adjunctive cilostazol added to clopidogrel on platelet function differed by type of platelet function test. VerifyNow % inhibition and PRI were more inhibited than the other platelet function tests. TRIAL REGISTRATION: CSPS.com substudy in TWMU (UMIN000026672), registered on April 1, 2017. This study was performed as a substudy of CSPS.com (UMIN000012180, registered on October 31, 2013) and was retrospectively registered.
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Inibidores da Agregação Plaquetária , Ticlopidina , Humanos , Clopidogrel/farmacologia , Cilostazol/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Testes de Função Plaquetária , Quimioterapia Combinada , Agregação PlaquetáriaRESUMO
Clinical flow cytometry tests for inherited and acquired platelet disorders are useful diagnostic tools but are not widely available. Flow cytometric methods are available to detect inherited glycoprotein deficiencies, granule release (secretion defects), drug-induced thrombocytopenias, presence of antiplatelet antibodies, and pharmacodynamic inhibition by antiplatelet agents. New tests take advantage of advanced multicolor cytometers and allow identification of novel platelet subsets by high-dimensional immunophenotyping. Studies are needed to evaluate the value of these new tests for diagnosis and monitoring of therapy in patients with platelet disorders.
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Transtornos Plaquetários , Plaquetas , Humanos , Plaquetas/fisiologia , Transtornos Plaquetários/diagnóstico , Anticorpos , Citometria de Fluxo/métodos , ImunofenotipagemRESUMO
INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. AREAS COVERED: In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. EXPERT OPINION: Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária , Síndrome Coronariana Aguda/tratamento farmacológico , Medicina de Precisão , Intervenção Coronária Percutânea/efeitos adversos , Cloridrato de Prasugrel , Hemorragia/induzido quimicamente , Resultado do Tratamento , Antagonistas do Receptor Purinérgico P2YRESUMO
BACKGROUND: Perinatal management of congenital platelet dysfunction represents a challenge. One of the major concerns is whether neuraxial anesthesia can be applicable for cesarean delivery. We present a patient with thrombasthenia who underwent emergency cesarean delivery. CASE PRESENTATION: A 34-year-old primipara was diagnosed with autosomal dominant thrombasthenia, which was not classified as any known type. A thorough examination revealed that adenosine diphosphate aggregation and collagen aggregation were suppressed. Platelet mapping of viscoelastic testing was used to observe the trajectory of platelet function during pregnancy, which was found to be normal to hypercoagulable until 38 weeks of gestation. On the basis of the results of testing and physiological status, we commenced spinal anesthesia and avoided prophylactic platelet transfusion. CONCLUSION: The platelet mapping of viscoelastic testing was rapid and simple, allowing repeated examinations. We could choose the appropriate anesthesia method and determine the necessity of blood transfusion for a pregnant patient with thrombasthenia.
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BACKGROUND: The response of platelets to activating stimuli and pharmaceutical agents varies greatly within the normal population. Current platelet function tests are used to measure end-point levels of platelet activation without taking the speed at which platelets activate into account, potentially missing vital metrics to characterize platelet reactivity. OBJECTIVES: To identify variability, to agonists and among individuals, in platelet activation kinetics and assess the impact of this on thrombus formation. METHODS: We have developed a bespoke real-time flow cytometry assay and analysis package to measure the rate of platelet activation over time using 2 parameters of platelet activation, fibrinogen binding and P-selectin exposure. RESULTS: The rate of platelet activation varied considerably within the normal population but did not correlate with maximal platelet activation, demonstrating that platelet activation rate is a separate and novel metric to describe platelet reactivity. The relative rate of platelet response between agonists was strongly correlated, suggesting that a central control mechanism regulates the rate of platelet response to all agonists. CONCLUSION: For the first time, we have shown that platelet response rate corresponds to thrombus size and structure, wherein faster responders form larger, more densely packed thrombi at arterial, but crucially not venous, shear. We have demonstrated that the rate of platelet activation is an important metric in stratifying individual platelet responses and will provide a novel focus for the design and development of antiplatelet therapy, targeting high-shear thrombosis without exacerbating bleeding at low shear.