De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

Effect of Anti?Platelet Therapy on Peri?Operative Blood Loss in Patients Undergoing Off?Pump Coronary Artery Bypass Grafting

Purpose:The purpose of this study was to review the effect of the pre?operative use of clopidogrel and aspirin on peri?operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG). Materials and Methods: A total of 1200 patients who underwent off?pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on?pump CABG, and the combined procedure were excluded from the study. Results: Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post?operatively, this was statistically significant. Re?exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients. Conclusion: The pre?operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.

Platelet Aggregation on Glass Surface under Physiological Flow Condition / 医用生物力学

Objective To investigate platelet aggregation on glass surface under physiological flow condition. Methods The polydimethylsiloxane (PDMS)-glass microchannel chips were fabricated by soft lithography. Anti-coagulant human peripheral whole blood was flowed through the microchannel chip at flow shear rate of 300 s-1 and 1 500 s-1, respectively. The fluorescence images of platelet aggregates formed on glass surface at the bottom of the microchannel were captured after 150 s using an inverted fluorescence microscope. The number of platelet aggregates, average size, surface coverage and average fluorescence intensity were quantified by image analysis. The glass surface was treated with oxygen plasma, BSA blocking or collagen modification to establish different surfaces for platelet aggregation. The hematocrit (Hct) of blood sample was adjusted, and the whole blood was treated with different anti-platelet agents. The platelet aggregation on glass surface was observed under the above experimental conditions. The platelet aggregations in healthy people and diabetic patients were also analyzed. Results Under the flow condition, platelet aggregation on glass surface was three-dimensional. Platelet aggregation was dependent on wall shear rate, the hydrophilicity of glass surface and Hct, and was mainly regulated by GPIIb/IIIa-fibrinogen and ADP-P2Y12 receptor pathways. The aggregation of platelets on the glass surface could also reflect the high activity of platelets in diabetic patients. Conclusions At the flow conditions of 300 s-1 and 1 500 s-1, platelet aggregation on glass surface is related to flow rate, protein adsorption, platelet related receptors and platelet activation state. In this study, a new model for microfluidic platelet function analysis without additional adhesion protein modification was established, and it could be used for clinical evaluation of platelet function.

Novedades de las guías de la Sociedad Europea de Cardiología 2020 sobre manejo del síndrome coronario agudo sin elevación persistente del segmento ST / News from the European Society of Cardiology 2020 guidelines on the management of acute coronary syndrome without persistent ST-segment elevation / Novidades da Sociedade Europeia de Cardiologia 2020 diretrizes sobre o tratamento da síndrome coronariana aguda sem elevação persistente do segmento ST

Las enfermedades cardiovasculares representan la primera causa de muerte en el mundo. El manejo de los síndromes coronarios ha avanzado formidablemente en los últimos 50 años, reduciendo el riesgo isquémico, a expensas del consiguiente aumento del riesgo hemorrágico. La Sociedad Europea de Cardiología publicó en el año 2020 la guía sobre el manejo de síndrome coronario agudo sin elevación del segmento ST, donde se destacan cambios en los algoritmos de estratificación de riesgo y la terapia antiplaquetaria y anticoagulante como dos de los aspectos principales. En el presente editorial se resumen las principales novedades publicadas en este documento.

Cardiovascular disease is the leading cause of death worldwide. The management of coronary syndromes has advanced dramatically in the last 50 years, reducing ischemic risk, but observing an increase in bleeding risk. The European Society of Cardiology published in 2020 the guideline on the management of acute coronary syndrome without ST-segment elevation, where changes in risk stratification algorithms and antiplatelet and anticoagulant therapy are highlighted as two of the main aspects. This editorial summarizes the main developments published in this document.

A doença cardiovascular é a principal causa de morte em todo o mundo. O manejo das síndromes coronarianas avançou dramaticamente nos últimos 50 anos, reduzindo o risco isquêmico, mas observando um aumento no risco de sangramento. A Sociedade Europeia de Cardiologia publicou em 2020 a diretriz sobre o manejo da síndrome coronariana aguda sem supradesnivelamento do segmento ST, onde as alterações nos algoritmos de estratificação de risco e na terapia antiplaquetária e anticoagulante são destacadas como dois dos principais aspectos. Este editorial resume os principais desenvolvimentos publicados neste documento.

Dual antiplatelet therapy for mild stroke and transient ischemic attack / 国际脑血管病杂志

Patients with mild stroke and transient ischemic attack (TIA) have a high risk of early recurrence or deterioration. Antiplatelet therapy has been recognized to reduce the risk of ischemic vascular events. All guidelines recommend antiplatelet therapy for patients with ischemic stroke. Dual antiplatelet therapy (DAPT) refers to the application of two drugs with different mechanisms to block platelet aggregation and prevent thrombosis. There are many combinations of DAPT, and its safety and effectiveness are still uncertain. This article reviews the efficacy and safety of DAPT in patients with mild stroke and TIA.

The clinical profile of patients with intracerebral hemorrhage after receiving acute coronary syndrome regimen in a tertiary hospital: A case series

@#Coronary heart disease, which includes acute coronary syndromes (ACS) is a major cause of death and morbidity. Treatment for this condition includes dual anti-platelet treatment combined with an anti-coagulant and an anti-dyslipidemic. Bleeding complications may occur and one fatal adverse event is intracerebral hemorrhage (ICH). ACS cases in a tertiary hospital for the years 2014-2018 showed that there were 7 patients who presented with symptomatic ICH after treatment administration that accounts for 0.01% of a total of 1,097 patients. These patients were over the age of 50, but with no sex predilection. Common comorbidities were hypertension and malignancy. All patients presented with acute onset neurologic deficits within 1-4 days after administration of ACS regimen, with ICH scores of 3-4 signifying a high mortality rate of 72-90%. 6 out 7 patients had significant volume of ICH with mass effects, and 1 with subarachnoid hemorrhage. This lead to poor outcome in all patients with 6 out of 7 mortalities and 1 left with substantial disability. It was found that given the total number of patients administered with the said treatment, there is a low incidence of ICH.

Effect of anti-platelet antibodies on the efficacy of immunoglobulin therapy and Treg/Th17 ratio in children with immune thrombocytopenia / 中国输血杂志

【Objective】 To investigate the relationship between anti-platelet antibodies, therapeutic effect of intravenous immunoglobulin (IVIG) and Treg/Th17 cells imbalance in children with immune thrombocytopenia (ITP). 【Methods】 The changes and correlation of platelet count and Treg/Th17 ratio before and after IVIG treatment in 60 newly diagnosed ITP children with anti-platelet antibodies and 60 children with primary ITP without anti-platelet antibodies were analyzed. 【Results】 1) Compared with the control group, the efficacy of IVIG treatment was better in children with ITP in the case group(CR+ R cases: 50 vs 32) (P<0.01). 2) After IVIG treatment, platelet count(×109/L)(case: 4.5±2.9 vs 327.4±69.5, control: 4.1±3.2 vs 304.7±75.9), Treg cell level(%)(case: 2.15±1.08 vs 5.09±1.37, control: 2.41±0.92 vs 4.98±1.10), Treg/Th17 ratio(case: 1.10±0.19 vs 7.75±1.11, control: 1.27±0.21 vs 4.69±0.81)significantly increased while Th17 cell level(%) significantly decreased in the 2 groups of children(case: 2.07±1.31 vs 1.37±0.92, control: 2.13±1.18 vs 1.48±1.01); compared with the control group, there was no significant change in Treg, Th17 and Treg/Th17 ratio before and after treatment in the case group (P>0.05), but platelet count increased more significantly (P<0.05). 3) There were 3 positive cases in the control group and 12 negative cases in the case group after IVIG treatment, and IVIG treatment probably had no effect on the positive rate of anti-platelet antibodies in children with ITP (P>0.05). 4) The change in platelet count after IVIG treatment was significantly positively correlated with Treg levels (r=0.49 in the case group and r=0.441 in the control group) and negatively correlated with Th17 cell levels (r=-0.390 in the case group and r=-0.364 in the control group). 【Conclusion】 Anti-platelet antibodies can be used as a predictor of the efficacy of IVIG therapy in children with ITP, but they are not associated with changes in the Treg/Th17 ratio.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Review of studies on Bulbine natalensis Baker (Asphodelaceae): Ethnobotanical uses, biological and chemical properties

Bulbine natalensis Baker is a native succulent herb that belongs to the family Asphodelaceae, and is regarded asprecious, highly valued, and extensively used throughout the continent for medicinal purposes and in treating maleimpotency due to the aphrodisiac and invigorating effect. This study reviews the status of B. natalensis ethnobotanicaluses, biological and chemical properties. This review was conducted from April 2019 to February 2020 by applyingthe mixed-method review approach, and in the framework of a complete description of B. natalensis species, dataon morphology, distribution, and economic importance were discussed. Pharmacological screening reported thatB. natalensis possesses anti-inflammatory and broad-spectrum antimicrobial properties. The bulbous plant vapourcontains substances such as tannins, anthraquinones, cardiac glycosides, saponins, and alkaloids. Scientific evaluationsfrom various researchers have substantiated the use of B. natalensis in the enhancement of male sexual disorders, cureof wounds, rashes, itches, ringworm, diabetes, rheumatism, cracked lips and herpes, diarrhea, and paroxysms amongother diseases.

Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivatives / 药学学报

Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method．The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

Advances in pharmacological effects of higenamine on cardiovascular system / 药学学报

Higenamine (HG) is an active cardiotonic component isolated from Aconite. Chinese and foreign scholars have done a lot of research on the metabolism and pharmacological effects of HG, which confirmed that it has cardiovascular pharmacological effects of cardiactonic action and vasodilation for the treatment of heart failure and bradycardia, anti-oxidative and anti-apoptotic effects which can be used to protect the heart and reduce heart ischemia and reperfusion injury. In addition, HG inhibits the expression of iNOS mRNA by inhibiting the activity of the transcription factor NF-κB, inhibits the lipopolysaccharide (LPS)-induced NO product, and inhibits platelet aggregation and thrombus formation, thereby improving the experimental septic shock in animals. This article reviews the recent progress in cardiovasular pharmacology of HG, which will contribute to the further development and clinical application of it in the future.

Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents / 中国天然药物

To search for potent anti-ischemic stroke agents, a series of tetramethylpyrazine (TMP)/resveratrol (RES) hybrids 6a-t were designed and synthesized. These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, 6d, 6g-i, 6o and 6q were more active than TMP. The most active compound 6h exhibited more potent anti-platelet aggregation activity than TMP, RES, as well as positive control ticlopidine (Ticlid) and aspirin (ASP). Furthermore, 6h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide (HO) or hydroxyl radical (·OH). Importantly, 6h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation (OGD/R) injury, comparable to an anti-ischemic drug edaravone (Eda). Together, our findings suggest that 6h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

Measurement of antiplatelet aggregation and potency of hirudo / 药学学报

The objective of this work was to develop a bioassay to quantify the antiplatelet aggregation activity of hirudo for quality evaluation and control. Antithrombin activity of hirudo extracted by high temperature decoction was determined by thrombin titration. Antiplatelet aggregation activity of hirudo was determined through pharmacodynamic experiments in vitro and in vivo using a bioassay we developed for quantifying inhibition of platelet aggregation. Methodological investigation was carried out and the titers of 12 batches of hirudo samples were determined. During the experiment, the disposal of animals is in accordance with the ethical standards of animal experiments. The results showed that the antithrombin activity of hirudo decocted at high temperature decreased significantly and almost lost its activity. Hirudo inhibited platelet aggregation and results in vivo and in vitro were consistent. These assays were employed to test 12 batches of hirudo. The results demonstrated that the biopotency of 12 batches was 113.49, 96.13, 121.22, 127.33, 83.48, 108.72, 131.41, 127.95, 76.90, 126.27, 132.89 and 573.53 U·mg-1. The method was reliable and reproducible and can be used to assess the quality of hirudo.

Anti-platelet aggregation mechanism of Xixian Tongshuan Preparation based on molecular simulation methods / 中国中药杂志

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.

Research Progress in Clopidogrel Resistance / 医药导报

Clopidogrel is one of the anti-platelet drugs, which is widely used in the world.It plays an important role in the treatment of patients with acute coronary syndrome and those undergoing percutaneous coronary intervention.Clopidogrel is effective in inhibiting the activity of platelets, decreasing the incidence of thrombosis in the stent, and then reducing the risk of adverse cardiovascular events in affected individuals. However, some patients still have coronary thrombosis after taking clopidogrel.This phenomenon is known as clopidogrel resistance or clopidogrel non-response or low response. Identification of clopidogrel resistance is of great significance in preventing the occurrence of adverse cardiovascular events.This paper provides guidance for the clinical treatment of clopidogrel resistance by discussing the definition, mechanisms and laboratory evaluation of clopidogrel resistance.

Study Progress in Signaling through Thromboxane A2 Receptors in Platelet and Anti-platelet Drugs / 中国药师

Thromboxane A2 receptors (TPs) widely distribute in different organ systems and localize both on cell membranes and in intracellular structures.TPs are the members of seven-transmembrane G-protein-coupled receptor (GPCR) super family.Historical-ly, the involvement of TPs in platelet functions has received the greatest attention .TPs have the capacity to activate different signaling cascades which regulate platelet shape change , aggregation and secretion response .Currently , anti-platelet drugs primarily act on re-ceptors and /or signaling molecules in activation pathways .The signaling transduction of TPs in platelet contributes to the investigation of the effects of extracts of traditional Chinese medicine on antiplatelet aggregation and the exploration of the action mechanisms .

Pharmacological actions of miltirone in the modulation of platelet function / 中国药理学与毒理学杂志

OBJECTIVE Salvia miltiorrhiza bunge contains various active constituents, some of which have been developed as commercially available medicine. Moreover, some other ingredients in Salvia miltiorrhiza play great roles in anti-platelet activity. The aim of the present study was to investi-gate the effects and the underlying mechanism of miltirone,a lipophilic compound of Salvia miltiorrhiza Bunge. METHODS The ability of miltirone to modulate platelet function was investigated by a variety of in vitro and in vivo experiments.Platelet aggregation and dense granule secretion induced by various agonists were measured with platelet aggregometer.Clot retraction and spreading were imaged by digital camera and fl uorescence microscope. Ferric chloride-induced carotid injury model and pulmonary thromboembolism model were used to check miltirone effect in vivo. To elucidate the mechanisms of anti-platelet activity of miltirone,flow cytometry and Western blotting were performed. RESULTS Miltirone (2,4,8 μmol·L-1)was shown to suppress platelet aggregation,dense granule and α granule secretion in a dose-dependent manner. Meanwhile, miltirone inhibited the clot retraction and spreading of washed platelets.It reduced the phosphorylation of PLCγ2,PKC,Akt,GSK3β and ERK1/2 in the down-stream signal pathway of collagen receptor.It also reduced the phosphorylation of Src and FAK in the integrin αⅡbβ3 mediated"outside-in"signaling,while it did not suppress the phosphorylation of β3.In addition, miltirone prolonged the occlusion time and reduced collagen/epinephrine induced pulmonary thrombi. CONCLUSION Miltirone suppresses platelet "inside-out" and "outside-in" signaling by affecting PLCγ2/PKC/ERK1/2, PI3K/Akt and Src/FAK signaling. Therefore, miltirone might represent a potential anti-platelet candidate for the prevention of thrombotic disorders.

Dental management of patients on anti-thrombotic agents

The number of geriatric patients seeking dental service is ever-rising because of increased life expectancy, also with problem of increased chronic medical conditions. One of them are patients on anti-thrombotic medication. Bleeding complication after minor oral surgery by anti-thrombotic agents is of concerns to dentists on dental management of these patients. Risk and benefit of the anti-thrombotic agents must be weighed before initiating dental procedures, which should be established as a treatment guideline. Purpose of the paper is to optimize the management of the dental patients on anti-thrombotic medication via standardization of treatment protocol of such a patient.

Chemical constituents from a Tibetan herbal medicine Corydalis hendersonii / 中国中药杂志

Nine alkaloids and two phenolic glycosides were isolated from EtOH extract of the whole plants of Corydalis hendersonii by various chromatographic techniques including silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified as groenlandicine (1), berberine (2), protopine (3), cryptopine (4), N-trans-feruloyloctopamine(5), 3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl] acrylamide (6), N-cis-p-coumaroyloctopamine (7), N-trans-p-coumaroylnoradrenline (8),N-cis-feruloyloctopamine (9), apocynin (10), and glucoacetosyringone (11) by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 10 and 11 were isolated from this genus for the first time, and 1, 2, and 5-9 were isolated from the species for the first time. All isolates were tested for their protection for in vitro PC12 cell line and antiplatelet aggregation activity. The results showed that compounds 5 and 7 displayed protective effects at a concentration of 10 μmol·L⁻¹, and compound 2 showed antiplatelet aggregation activity induced by THR, ADP, and AA, and compound 3 exhibted inhibitory effect induced by THR.

Uso de terapia antiagregante dual luego de angioplastía coronaria: duración, frecuencia de sangramientos y validación de scores de riesgo de hemorragia en una cohorte chilena / Dual anti platelet therapy post PTCA: duration, bleeding risk and validation of scores for predicting risk of bleeding in a Chilean population

Resumen: Introducción: La terapia antiagregante dual (TAD) con aspirina más clopidogrel o ticagrelor es fundamental para prevenir trombosis de stent y nuevos eventos cardiovasculares (CV) en pacientes sometidos a angioplastía coronaria (AC). Sin embargo, TAD se asocia a un riesgo aumentado de hemorragias, en particular cuando su uso se prolonga. Recientemente se han creado puntajes (DAPT, PRECISE-DAPT) que buscan estimar el riesgo de sangrado en pacientes con TAD por tiempo prolongado, los que quisimos evaluar en nuestra población. Métodos: Se utilizó la base de datos prospectiva de Prevención Cardiovascular del Hospital Clínico U. Católica, seleccionando pacientes sometidos a AC el año 2015. Se realizó una encuesta telefónica estandarizada para identificar episodios de sangrado definidos según clasificación ISTH, tiempo de uso de TAD y nuevos eventos CV. Se calcularon los puntajes DAPT y PRECISE-DAPT. Se usó pruebas de t de Student, test exacto de Fisher y curva ROC, según correspondiese, considerando significativa una p<0,05. Resultados: Se incluyeron 227 pacientes (edad 64,2±12,3 años, 22,5% mujeres), de los cuales el 69,6% eran hipertensos, 28,6% diabéticos, 26,9% fumadores y 5,3% insuficientes renales crónicos. En el 63% de los pacientes la AC fue por síndrome coronario agudo, se implantaron 1,4±0,7 stents/paciente y el 37% de los pacientes recibió sólo stents metálicos. Al momento de la encuesta, el seguimiento fue de 26±3 meses. Se registró un tiempo promedio de duración de TAD de 12,6±7,4 meses, con 99,1% de los pacientes recibiendo aspirina, 93,4% clopidogrel, 6,6% ticagrelor y 9,3% anticoagulantes orales. Hubo 35 (15,4%) nuevos eventos CV (revascularización 14, infarto 12, accidente cerebrovascular 2 y muerte 7) y 31 (13,6%) episodios de sangrados (criterio ISTH). De acuerdo con el criterio TIMI de sangrado se registraron 5 (2,2%) episodios graves, 9 (3,9%) leves y 17 (7,4%) menores. En 10 (4,4%) pacientes se modificó la TAD debido al sangrado. PRECISE-DAPT se asoció de manera significativa a los episodios de sangrado (p<0,01); tener un puntaje de alto riesgo (>25) aumentó más de 3 veces el riesgo de sangrado (OR 3,1 IC 1,4-7,1, p<0,01) y una curva ROC estableció que en la población estudiada el mejor punto de corte fue de 18 puntos (C-statistic 0,69) (Figuras 1A y B). El uso de TACO aumentó el riesgo (OR 3,4 IC 1,2-9,5, p=0,02). Si bien miden distintos parámetros, los puntajes de riesgo DAPT y PRECISE-DAPT se correlacionaron significativamente en nuestra cohorte (p<0,01). Conclusiones: En esta cohorte de la vida real se demuestra que la ocurrencia de sangramientos es un evento frecuente en pacientes con TAD, similar a la tasa de nuevos eventos CV, y por tanto debe ser un factor relevante a considerar al momento de la AC y la selección de la TAD. El puntaje PRECISE-DAPT es una herramienta útil para predecir sangrados, aunque nuestros resultados sugieren que en población chilena los valores de corte pueden ser algo menores que lo previamente publicado .

Abstracts: Background: Dual antiplatelet therapy (DAT) with aspirin plus clopidogrel or ticagrelor is essential for the prevention of stent thrombosis and new cardiovascular events in patients undergoing PCI. However, DAT is associated with an increased risk of bleeding, more so when it is used for prolonged time periods. Scores (DAPT, PRECISE-DAPT) developed to predict bleeding risk were evaluated in this study. Method: The prospective Cardiovascular Prevention database at Catholic University Hospital was used to select patients who underwent PCI followed by DAT during 2015. By phone contact information on bleeding episodes - according to the ISTH classification -, new cardiovascular events and DAT duration were collected. DAPT and PRECISE- DAPT scores were calculated. Student's t test, Fisher exact test and ROC analysis were used. Significance was established at p< 0.05. Results: 277 patients were included (age 64.2±12.3 y-o, 22.5% women). Hypertension was present in 66.9%, diabetes in 28.6%, smoking habit in 26.9% and renal failure in 5.3%. The indication for PCI was acute coronary syndrome in 63%, 1.4±0.7 stents per patient were implanted and 37% of patients received bare metal stents exclusively. Follow-up extended for 26±3 months. DAT was active for 12.6±7.4 months and 9.3% of patients received oral anticoagulant therapy. There were 35 (15.4%) new cardiovascular events (14 revascularizations, 12 myocardial infarctions, 2 CVA and 7 deaths). Conversely, there were 31 (13.6%) bleeding episodes. According to the TIMI classification, bleeding episodes were severe in 2.2%, mild in 3.9% and minor in 7.4%. In 4% of patients DAT was modified due to bleeding. PRECISE-DAPT score was significantly associated to bleeding episodes (p<0.01). A high score (>25) was associated with a 3-fold risk of bleeding (OR 3.1, CI 1.4-7.1 (p<0.01). Through ROC analysis the best PRECISE-DAPT cutting point in this cohort was 18 (C=0.69). The use of oral anticoagulation increased bleeding risk (OR 3.4 CI 1.2 - 9.5, p=0.02). DAPT and PRECISE-DAPT were significantly correlated (p<0.01). Conclusion: Bleeding is a frequent complication of DAT, similar to the risk of new cardiovascular events. PRECISE-DAPT score is useful to estimate the risk of bleeding, although this study suggests that in the studied population the cutting point may be somewhat lower than previously published.