Antitrombóticos: investigación y aplicaciones en la atención médica / Antithrombotics: Research and applications in healthcare

Resumen: Los antitrombóticos son fármacos que se utilizan para prevenir la formación de coágulos sanguíneos, también conocidos como trombos. Estos coágulos pueden causar graves problemas de salud, como infartos o enfermedades cerebrovasculares. En este artículo se analizan diferentes tipos de antitrombóticos, como los antiplaquetarios y los anticoagulantes, y se discuten sus mecanismos de acción. Además, se examinan los beneficios y los riesgos asociados con el uso de antitrombóticos. Por un lado, estos fármacos pueden reducir el riesgo de eventos trombóticos, lo que puede ser especialmente beneficioso en pacientes con condiciones de alto riesgo, como aquellos que han sufrido un infarto o que tienen fibrilación auricular. Por otro lado, también se discuten los posibles efectos secundarios de los antitrombóticos, como el aumento del riesgo de sangrado. Además, se proporcionan pautas para su uso seguro en diferentes escenarios clínicos. Finalmente, se abordan las estrategias de monitoreo y ajuste de la dosis de estos medicamentos para garantizar su eficacia y seguridad en los pacientes.

Abstract: Antithrombotics are drugs used to prevent the formation of blood clots, also known as thrombi. These clots can cause serious health problems, such as heart attacks or strokes. Different types of antithrombotics, such as antiplatelets and anticoagulants, are analyzed and their mechanisms of action are discussed. Additionally, the benefits and risks associated with the use of antithrombotics are examined. On the one hand, these drugs can reduce the risk of thrombotic events, which may be especially beneficial in patients with high-risk conditions, such as those who have suffered a heart attack or who have atrial fibrillation. On the other hand, the possible side effects of antithrombotics, such as the increased risk of bleeding, are also discussed and guidelines for their safe use in different clinical scenarios are provided. Additionally, monitoring and dose adjustment strategies for these medications are addressed to ensure their effectiveness and safety in patients.

Fondaparinux versus Enoxaparina no Tratamento de Pacientes Obesos com Síndrome Coronariana Aguda / Fondaparinux versus Enoxaparin in the Treatment of Obese Patients with Acute Coronary Syndrome

Resumo Fundamento: O fondaparinux é um anticoagulante eficaz e seguro usado no tratamento de síndromes coronarianas agudas (SCAs). No entanto, devido à baixa representatividade de indivíduos obesos em ensaios clínicos, os efeitos de se aplicar os resultados desse medicamento nesta população continuam incertos. Objetivos: Comparar o fondaparinux à enoxaparina no tratamento de obesos com SCA. Métodos: Este é um estudo do tipo coorte retrospectivo, incluindo indivíduos obesos (IMC ≥ 30 Kg/m2) internados com Infarto do Miocárdio sem Elevação do Segmento ST (IAMSSST) ou Angina Instável (AI) e tratados com fondaparinux ou enoxaparina entre 2010 e 2020. Os grupos que receberam fondaparinux e enoxaparina foram comparados quanto suas características clínicas e laboratoriais usando o teste do qui-quadrado e o teste de Mann-Whitney, conforme apropriado. A incidência dos desfechos primários (morte, reinfarto, acidente vascular cerebral, sangramento maior) foi comparada entre os grupos. Um p<0,05 foi considerado estatisticamente significativo em todas as análises. Resultados: Um total de 367 pacientes obesos com IAMSSST ou AI foi incluído, dos quais 258 usaram fondaparinux e 109 usaram enoxaparina. A idade média foi 64 ± 12 anos, 52,9% eram do sexo masculino. A prevalência e diabetes, hipertensão, dislipidemia, doença arterial coronariana prévia, acidente vascular cerebral prévio, e implementação de estratégia invasiva foi similar entre os grupos. A incidência do desfecho primário foi 4,7% no grupo fondaparinux e 5,5% no grupo enoxaparina (p = 0,729). Não houve diferença entre os grupos quando os componentes do desfecho primário foram analisados separadamente. Conclusão: Em uma amostra de pacientes obesos com IAMSSST ou AI, não houve diferença na ocorrência do desfecho composto (morte, acidente vascular cerebral, reinfarto, sangramento maior) entre os pacientes que utilizaram fondaparinux ou enoxaparina.

Abstract Background: Fondaparinux is an effective and safe anticoagulant in the treatment of acute coronary syndromes (ACS). However, due to the low representation of obese individuals in clinical trials, the effects of applying the results of this drug to this population remain uncertain. Objectives: To compare Fondaparinux to Enoxaparin in the treatment of obese patients with ACS. Methods: This is a retrospective cohort study, including obese individuals (BMI ≥ 30 Kg/m2) admitted with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and treated with Fondaparinux or Enoxaparin between 2010 and 2020. The Fondaparinux and Enoxaparin groups were compared for their clinical and laboratory characteristics using chi-square and Mann-Whitney tests, as appropriate. The incidence of primary outcomes (death, reinfarction, stroke, major bleeding) was compared between groups. P-value < 0.05 was considered significant for all analyses. Results: A total of 367 obese patients with NSTEMI or UA were included, of whom 258 used Fondaparinux and 109 used Enoxaparin. Mean age was 64 ± 12 years, and 52.9% were male. The prevalence of diabetes, hypertension, dyslipidemia, prior coronary artery disease, prior stroke, and implementation of invasive strategy was similar between groups. The incidence of the primary outcome was 4.7% in the Fondaparinux group and 5.5% in the Enoxaparin group (p = 0.729). There was no difference between groups when analyzing the components of the primary outcome separately. Conclusion: In a sample of obese patients with NSTEMI or UA, there was no difference in the occurrence of the composite outcome (death, stroke, reinfarction, major bleeding) between patients who used Fondaparinux or Enoxaparin.

Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA) / Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA)

Resumo Fundamento: Os ensaios clínicos demonstraram a segurança da Edoxabana, um anticoagulante oral não dependente de vitamina K (NOAC), e a sua eficácia na prevenção de acidente vascular cerebral e embolia sistémica em pacientes com fibrilação atrial não valvar (FANV) e também na prevenção e tratamento de tromboembolismo venoso. No entanto, pesquisas adicionais são necessárias para avaliar a segurança e a eficácia da Edoxabana em um cenário real na população brasileira. Objetivo: A fim de compreender os riscos e benefícios do uso da Edoxabana em cenários clínicos de rotina, o estudo EdoBRA está sendo conduzido para obter informações sobre a segurança e eficácia do uso da Edoxabana em pacientes não pré-selecionados com FANV no Brasil. Métodos: O estudo EdoBRA é um estudo multicêntrico, prospectivo e observacional, realizado em 36 centros no Brasil. São elegíveis para este estudo pacientes com FANV, ≥ 18 anos de idade, tratados com Edoxabana disponível comercialmente, que iniciaram o tratamento por pelo menos 14 dias e não mais do que 90 dias antes da data de inclusão no estudo, e que não estão participando de nenhum outro estudo de intervenção. Ao todo, 700 pacientes devem ser inscritos e acompanhados por um ano, com coletas de dados programadas para o período basal e 3, 6 e 12 meses após a inscrição no estudo. O objetivo primário de segurança é o sangramento clinicamente relevante (de acordo com critérios da Sociedade Internacional de Trombose e Hemostasia - ISTH), e o objetivo secundário de eficácia são desfechos cardiovasculares relevantes relacionados à FANV. Conclusão: O estudo observacional EdoBRA gerará informações adicionais relevantes sobre a Edoxabana enquanto NOAC em diversos aspectos do manejo de pacientes no atendimento clínico de rotina, como perfil de segurança e efetividade em pacientes com FANV no Brasil.

Abstract Background: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. Objective: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. Methods: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. Conclusion: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise / Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis

Resumo Fundamento: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. Objetivos: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. Métodos: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. Resultados: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). Conclusões: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Abstract Background: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. Objectives: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. Methods: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. Results: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). Conclusions: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

Actividad biológica in vitro de los extractos acuosos y alcohólicos de tubérculos andinos

Introducción: La medicina ancestral ha utilizado plantas con cualidades medicinales para prevenir y tratar enfermedades; aun cuando este tipo de investigaciones se han incrementado, son escasos los estudios con tubérculos andinos. Objetivo: Determinar la actividad biológica de extractos acuosos y etanólicos de los tubérculos andinos Tropaeolum tuberosum (mashua) y Ullucus tuberosus (melloco). Métodos: La investigación fue experimental y se desarrolló in vitro. La muestra estuvo constituida por 2 tubérculos andinos utilizados en la medicina ancestral. Se aplicaron técnicas de extracción en medio acuoso y etanólico. Los extractos fueron evaluados para determinar la actividad hemoaglutinante, anticoagulante y antimicrobiana con cepas ATCC. Resultados: Se demostró actividad hemoaglutinante en el extracto acuoso de T. tuberosum sobre eritrocitos A. Todos los extractos acuosos mostraron actividad anticoagulante, Tropaeolum tuberosum inhibió la actividad de la coagulación sanguínea (vía intrínseca) con un TTPa> 300 seg. Tanto los extractos acuosos y etanólicos exhibieron actividad antimicrobiana contra cepas ATCC, Tropaeolum tuberosum inhibió el crecimiento de Staphylococcus aureus 25923 con halos de 17 y 22 mm y Ullucus tuberosus (blanco) con halos de 10 y 30 mm, respectivamente. Los extractos acuosos de Tropaeolum tuberosum y Ullucus tuberosus (rojo) inhibieron el crecimiento de Candida tropicalis 66029 con halos de 27 y 12 mm y respectivamente. Conclusiones: Determinada la actividad biológica, se evidencia que los tubérculos andinos estudiados aglutinan eritrocitos humanos, específicamente eritrocitos del grupo A, así mismo, capacidad de inhibir las proteínas plasmáticas de la coagulación y de inhibir el crecimiento bacteriano y micótico de cepas ATTC.

Introduction: Ancestral medicine has used plants with medicinal qualities to prevent and treat diseases, even though this type of research has increased, studies with Andean tubers are scarce. Objective: To determine the biological activity of aqueous and ethanolic extracts of the Andean tubers Tropaeolum tuberosum (mashua) and Ullucus tuberosus (melloco). Methods: The research was experimental and was developed in vitro. The sample consisted of 2 Andean tubers used in ancestral medicine. Extraction techniques were applied in aqueous and ethanolic medium. The extracts were evaluated for hemagglutinating, anticoagulant and antimicrobial activity with ATCC strains. Results: Hemagglutinating activity was demonstrated in the aqueous extract of T. tuberosum on A erythrocyte. All aqueous extracts showed anticoagulant activity, Tropaeolum tuberosum inhibited blood coagulation activity (intrinsic pathway) with an aPTT>300 sec. Both aqueous and ethanolic extracts exhibited antimicrobial activity against ATCC strains, Tropaeolum tuberosum inhibited the growth of Staphylococcus aureus 25923 with halos of 17 and 22 mm and Ullucus tuberosus (white) with halos of 10 and 30 mm, respectively. The aqueous extracts of Tropaeolum tuberosum and Ullucus tuberosus (red) inhibited the growth of Candida tropicalis 66029 with halos of 27 and 12 mm, respectively. Conclusions: Once the biological activity was determined, it was evident that the Andean tubers studied agglutinated human erythrocytes, specifically group A erythrocytes, as well as the ability to inhibit plasma coagulation proteins and inhibit the bacterial and fungal growth of ATTC strains.

A study on drug utilization pattern of anticoagulants in post-cardiac surgeries at a tertiary care hospital

Background: The study is being carried out mainly to understand the prevention of coagulation of blood after a patient undergoing various types of cardiac surgeries, using different anticoagulation therapies suitable to particular types of cardiac surgery. This study was conducted to know the types of anticoagulants prescribed to patients who have undergone different types of cardiac surgeries along with the prescribed anticoagulants. Methods: The study method used was a retrospective and prospective observational study carried out on 50 patients who underwent cardiac surgeries in the department of cardiology and medicine. Results: A total of 50 patients were enrolled for this study who satisfied the inclusion criteria, out of which 64% of patients were males, and 36% were females. The highest number of patients were found to be in between the age group of 61-70 yrs (34%), whereas age group between 51-60 yrs (28%), age group 71 and above (18%), 41-50 (14%), 21-30 yrs (4%) and 18-20 yrs (2%) respectively. Most of the patients had undergone Coronary Artery bypass grafting. It was seen that the highest Anticoagulant being prescribed was Heparin in most of the post-cardiac surgeries. Whereas drugs like dalteparin, acenocoumarol, and warfarin were prescribed the majority in valvular heart surgeries. Conclusions: Various cardiac surgeries were taken into consideration for the study. The most common anticoagulants prescribed were heparin, dalteparin, acenocoumarol, and warfarin in coronary artery bypass surgery and valvular heart surgeries respectively.

ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.

Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery / 中国药房

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Vertebral fractures combined with prolonged activated partial prothrombin time:A case report / 北京大学学报(医学版)

With the development of modern medical standards,autoimmune diseases and their associ-ated successive osteoporosis have received increasing attention in recent years.Patients with autoimmune diseases,due to the characteristics of the disease and the prolonged use of glucocorticoid hormone thera-py,may affect the bone formation and bone absorption of the patient,followed by severe successive osteo-porosis,thereby increasing the risk of osteoporotic vertebral fractures.Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures.Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases.Percutaneous vertebro-plasty(PVP)and percutaneous kyphoplasty(PKP)are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures.However,due to the operation of spinal puncture during the operation,there are serious surgical risks such as bone cement leakage,spinal epidural hemorrhage,subdural hemorrhage,and subarachnoid hemorrhage in both PVP and PKP.As a result,it is necessary to evaluate the patient's body before surgery carefully,especially in the case of blood coagulation.This article reports a case of autoimmune disease patient admitted to Peking University People's Hospital due to lumbar 4 vertebral compression fracture combined with Sj?gren's syn-drome.The patient's preoperative examination showed that the activated partial thromboplastin time(APTT)was significantly prolonged.After completing the APTT extended screening experiment and lu-pus anticoagulant factor testing,the multi-disciplinary team(MDT)of Peking University People's Hospi-tal jointly discussed the conclusion that the patient's test results were caused by an abnormal self-immuni-ty anti-copulant lupus(LAC).Based on the results of the laboratory examination,the patient was con-sidered to be diagnosed with combined antiphospholipid syndrome(APS).For such patients,compared with the patient's tendency to bleed,we should pay more attention to the risk of high blood clotting in the lower limbs of the patient,pulmonary clots and so on.With timely anti-coagulation treatment,the patient safely passed the peripheral period and was successfully discharged from the hospital.Therefore,for pa-tients with autoimmune diseases with prolonged APTT in the perioperative period,doctors need to careful-ly identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

Aspirin for thromboprophylaxis in orthopedic surgery: advancements in clinical evidence and guidelines / 中华创伤骨科杂志

As patients undergoing orthopedic surgery are a high-risk group for venous thromboembolism (VTE), clinical guidelines suggest anticoagulant drugs for VTE prophylaxis during perioperative period. Global antithrombotic guidelines vary in recommendations for anticoagulant drugs, but there is a general consensus in favor of using low-molecular-weight heparin (LMWH) as the first choice for prophylaxis, followed by unfractionated heparin, fondaparinux, warfarin, aspirin, and other direct oral anticoagulants (DOACs). Of them, aspirin is an inexpensive, widely used antiplatelet drug with limited complications and clear efficacy in prevention of myocardial infarction, stroke, and certain specific cancers. It was also used early for venous thromboembolism prophylaxis in orthopedic patients after surgery. Clinical experience of orthopedic physicians in North America has shown the effectiveness of aspirin in VTE prevention over several decades so that aspirin continues to be used to this day, but its use for VTE prophylaxis is less common in Europe and Asia. Historically, the role and efficacy of aspirin in VTE prevention have been the subjects of considerable controversy, for the early and recent research findings contradict each other, and recommendations conflict in different guidelines. This review focuses on the advancements in clinical evidence and guideline recommendations regarding the use of aspirin for VTE prophylaxis in major orthopedic surgeries.

Embolic stroke of undetermined source: knowledge validated and refuted in the past 10 years / 中华神经科杂志

Embolic stroke of undetermined source (ESUS) is a concept proposed by an international working group in 2014 to define a class of stroke patients and explore the rationality of secondary prevention by anticoagulation in them. During the decade since the concept was proposed, numerous studies have been conducted on the pathogenesis and prevention strategies of ESUS. However, the research results are not quite consistent with the speculations and assumptions when the concept was proposed. Based on the review of the findings of related studies over the past decade, this article discusses the inherent defects in the ESUS concept, the new idea derived from the research results, the future role of ESUS, and trends in etiological diagnosis of ischemic stroke.

Research Progress on the Effect of Abnormal Thyroid Function on the Coagulation System and the Interaction of Therapeutic Drugs / 医药导报

For patients with abnormal thyroid function,the detection of peripheral blood coagulation indicators may be irregular,and there is a potential risk of thrombosis or bleeding.Patients with hyperthyroidism have significant endothelial dysfunction and risk of thrombosis.However,the reports on the effect of hypothyroidism on coagulation function are still controversial.The potential risk of abnormal thyroid function to the coagulation system may interfere with the safety of anticoagulant therapy,and the interaction between thyroid disease treatment drugs and anticoagulant drugs also affects the safety of the patient's medication.Therefore,this article is based on previous research literature,analyzes the correlation between abnormal thyroid function and coagulation function,and evaluates and discusses the impact of abnormal thyroid function on the coagulation system and related therapeutic drug interactions.It is expected to provide a reference for diagnosing and treating patients with thyroid dysfunction and abnormal coagulation function.

Clinical Comprehensive Evaluation of Oral Anticoagulants Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition) / 医药导报

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Falta de Uso de Anticoagulantes em Pacientes com Fibrilação Atrial e Risco Aumentado de Eventos Tromboembólicos de Acordo com o Sexo: Insights de um Estudo Multicêntrico Brasileiro / Lack of Anticoagulant Use in Patients with Atrial Fibrillation and Increased Risk of Thromboembolic Events According to Sex: Insights from a Multicentric Brazilian Study

Resumo Fundamento A fibrilação atrial (FA) é a arritmia cardíaca mais prevalente e sua apresentação difere de acordo com a idade e o sexo. Estudos recentes revelaram diferenças na FA entre vários grupos demográficos, incluindo a população latino-americana. Objetivos Melhor compreender as possíveis disparidades na prevalência da FA e nas estratégias de tratamento na população brasileira por meio de dados de um registro prospectivo multicêntrico de grande escala. Métodos O registro de FA da Rede D'Or é um estudo observacional prospectivo multicêntrico que incluiu pacientes com idade ≥ 18 anos com FA atendidos no pronto-socorro de 32 hospitais terciários no Brasil. Os pacientes foram caracterizados de acordo com o sexo e outras características basais e classificados de acordo com o uso prévio de anticoagulantes. Foi analisada a falta de uso de anticoagulantes em pacientes com indicações prévias. A significância estatística foi estabelecida em 5%. Resultados Os dados do estudo foram provenientes de um total de 1.955 pacientes inscritos. O sexo masculino foi mais prevalente e os homens eram mais jovens que as mulheres. Devido ao aumento da prevalência de episódios anteriores de FA e a um escore CHA2DS2-VASc mais elevado, mais mulheres tiveram indicação de terapia anticoagulante; no entanto, uma proporção significativa não estava recebendo esse tratamento. Dos 29 óbitos intra-hospitalares, 15 pacientes tinham indicação prévia para anticoagulação, mas apenas 3 estavam em uso de anticoagulantes. Conclusão O presente estudo revelou diferenças relacionadas ao sexo na população brasileira de pacientes com FA que são consistentes com tendências em países de alta renda. A promoção de uma melhor implementação de terapias anticoagulantes e antitrombóticas para reduzir o risco de óbito e eventos tromboembólicos entre mulheres com FA no Brasil é crucial.

Abstract Background Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and its presentation differs according to age and sex. Recent studies have revealed differences in AF among various demographic groups, including the Latin American population. Objectives To better understand potential disparities in AF prevalence and treatment strategies in the Brazilian population through data from a large multicentric prospective registry. Methods The Rede D'Or AF registry is a multicenter prospective observational study including patients aged ≥ 18 years with AF who were seen in the emergency department of 32 tertiary hospitals in Brazil. Patients were characterized according to sex and other baseline characteristics and were classified according to previous anticoagulant use. The lack of anticoagulant use in patients with previous indications was analyzed. Statistical significance was set at 5%. Results The study data were from a total of 1955 patients enrolled. Male sex was more prevalent, and men were younger than the women. Due to an increased prevalence of previous AF episode and a higher CHA2DS2-VASc score, more women had indications for anticoagulant therapy; however, a significant proportion was not receiving this treatment. From 29 in-hospital deaths, 15 patients had previous indication for anticoagulation, but only 3 were using anticoagulants. Conclusion This study revealed sex-related differences in the Brazilian population of patients with AF that are consistent with trends in high-income countries. The promotion of better implementation of anticoagulant and antithrombotic therapies to reduce the risk of death and thromboembolic events among women with AF in Brazil is crucial.

Diretrizes sobre trombose venosa profunda da Sociedade Brasileira de Angiologia e Cirurgia Vascular / Guidelines on deep vein thrombosis of the Brazilian Society of Angiology and Vascular Surgery

Resumo Trombose venosa profunda é uma das principais causas de morbidade hospitalar e ambulatorial, seja em pacientes clínicos, seja em pacientes cirúrgicos, impactando significativamente nas estatísticas de mortalidade, exigindo um diagnóstico rápido para que se institua de forma imediata o tratamento. O presente documento foi preparado e revisado por onze especialistas certificados pela Sociedade Brasileira de Angiologia e Cirurgia Vascular, que buscaram nas principais bases de dados as melhores evidências referentes à abordagem diagnóstica (exame físico, exames de imagem) e terapêutica (heparina, cumarínicos, anticoagulantes orais de ação direita, fibrinolíticos) da doença.

Abstract Deep vein thrombosis is one of the main causes of inpatient and outpatient morbidity, both in medical and surgical patients, significantly impacting mortality statistics and requiring prompt diagnosis so that treatment can be initiated immediately. This document was prepared and reviewed by 11 specialists certified by the Brazilian Society of Angiology and Vascular Surgery, who searched the main databases for the best evidence on the diagnostic (physical examination, imaging) and therapeutic approaches (heparin, coumarins, direct oral anticoagulants, fibrinolytics) to the disease.

Factores asociados a la adherencia al tratamiento en pacientes con anticoagulación oral

Introducción: El tratamiento con anticoagulantes ha demostrado su eficacia en la prevención de complicaciones cardioembólicas; sin embargo, la adherencia probablemente tiene el mayor impacto en la calidad de la anticoagulación. Objetivo: Determinar los factores que influyen en la adherencia al tratamiento anticoagulante y en la estabilidad del índice de estandarización internacional (INR). Métodos: Se realizó un estudio analítico, observacional y prospectivo que se corresponde con un estudio farmacoepidemiológico de utilización de medicamentos (Esquema Terapéutico), en pacientes con diagnóstico de trastornos de la coagulación, en el área de salud del municipio Manzanillo, entre el 1ro de septiembre de 2018 al 1ro de diciembre de 2020. Los datos de la investigación se obtuvieron de una entrevista y su historia clínica. Fueron utilizados el test del Xi-cuadrado (X2), t de Student, ANOVA y Kruskall Wallis, con un valor de p=0,05 durante el procesamiento estadístico. Resultados: Se constató un grado bajo de adherencia farmacoterapéutica en la población estudiada. Las variables sociodemográficas relacionadas con la adherencia terapéutica fueron el sexo, la escolaridad y la ocupación. Existe relación entre los recursos económicos, el conocimiento que tiene el paciente sobre su enfermedad, el cumplimiento del tratamiento no farmacológico y el cumplimiento del tratamiento farmacológico con la adherencia. Las reacciones adversas y la disponibilidad de los medicamentos fueron los factores dependientes del tratamiento relacionados con la adherencia. Las orientaciones del médico al paciente, el seguimiento del paciente y la relación médico-paciente, fueron los factores dependientes del médico. Conclusiones: Las cinco dimensiones de la adherencia terapéutica que plantea la OMS (factores socioeconómicos, relacionados con el paciente, relacionados con la enfermedad, relacionados con el tratamiento y relacionados con el sistema de salud) se asociaron con la adherencia al tratamiento y la estabilidad del índice de estandarización internacional.

Introduction: Anticoagulant therapy has demonstrated efficacy in preventing cardioembolic complications. However, adherence is probably the most important determinant of the quality of anticoagulation. Objective: The aim of this research wasto determine the factors that influence adherence to anticoagulation therapy and the stability of the international normalized ratio (INR). Methods: Between September 1, 2018 and December 1, 2020was conducted an analytical, observational andprospective study, corresponding to a pharmacoepidemiological study of drug utilization (Therapeutic Scheme). The object of this study were patients with a diagnosis of coagulation disorders, in the health area of the municipality of Manzanillo. The research data were obtained through an interview and their clinical history. The Xi-squared test (X2), Student's t-test, ANOVA and Kruskall Wallis were used, with a value of p = 0.05 in statistical processing. Results: As a result, a low level of pharmacotherapeutic adherence was observed in the studied population. The sociodemographic variables associated with adherence were sex, education and occupation. There was an association between economic resources, patients' knowledge of their disease, compliance with nonpharmacological treatment, and compliance with pharmacological treatment and adherence. Also, adverse drug reactions and drug availability were the treatment-related factors associated with adherence. And, physician orientation to the patient, patient follow-up, and physician-patient relationship were the physician-dependent factors. Conclusions: To sump up, the five dimensions of adherence proposedbyWHO (socioeconomic, patient-related, disease-related, treatment-related and health system-related factors) were associated with adherence and stability of the international standardization index.

Introdução: A terapêutica anticoagulante tem-se revelado eficaz na prevenção de complicações cardioembólicas. Objetivo: O objetivo desta investigação foi determinar os factores que influenciam a adesão à terapêutica anticoagulante e a estabilidade do rácio normalizado internacional (INR). Métodos: Um estudo analítico, observacional e prospetivo, correspondente a um estudo farmacoepidemiológico de utilização de medicamentos (Esquema Terapêutico) foi realizado entre 1 de setembro de 2018 e 1 de dezembro de 2020.O objeto deste estudo foram pacientes com diagnóstico de distúrbios de coagulação, da área de saúde do município de Manzanillo. Os dados da pesquisa foram obtidos através de uma entrevista e sua história clínica. Utilizou-se o teste do Xi-quadrado (X2), teste t de Student, ANOVA e Kruskall Wallis, com um valor de p = 0,05 no processamento estatístico. Resultados: Como resultado, observou-se um baixo nível de adesão à farmacoterapia na população estudada. As variáveis sociodemográficas associadas à adesão foram sexo, escolaridade e ocupação. Observou-se associação entre recursos financeiros, conhecimento da doença pelo paciente, adesão ao tratamento não farmacológico e adesão ao tratamento farmacológico e adesão. Além disso, as reacções adversas a medicamentos e a disponibilidade de medicamentos foram os factores relacionados com o tratamento associados à adesão. E a orientação médico-paciente, o acompanhamento do paciente e a relação médico-paciente foram os factores dependentes do médico. Conclusões: Concluindo, as cinco dimensões da adesão propostas pela OMS (factores socioeconómicos, relacionados com o doente, relacionados com a doença, relacionados com o tratamento e relacionados com o sistema de saúde) estiveram associadas à adesão e à estabilidade do índice de normalização internacional.

Características clínicas de pacientes con accidente cerebrovascular isquémico y fibrilación auricular internados en hospital de referencia durante el periodo 2021 a 2022

Introducción: se ha demostrado que uno de cada tres accidentes cerebrovasculares (ACV) isquémicos es consecuencia de una fibrilación auricular (FA) no conocida y, por ende, no tratada. Por eso es de vital importancia el diagnóstico y tratamiento oportuno de la FA, ya que el ACV isquémico es un motivo frecuente de ingreso hospitalario. Objetivos: determinar las características clínicas de pacientes con ACV isquémico y FA internados en el Hospital XX, durante los años 2021 y 2022. Metodología: se realizó un estudio observacional, descriptivo, de corte transversal, retrospectivo. Se incluyeron pacientes de ambos sexos, mayores de edad, con FA y ACV isquémico confirmados por electrocardiograma y tomografía. Las variables se obtuvieron de los expedientes clínicos. La investigación fue aprobada por el comité de ética de la Universidad Nacional de Itapúa. Resultados: se estudiaron 113 pacientes. La edad media fue 69 ± 10 años, el 54,87% (62) fueron varones. Entre los factores de riesgo, 96,46% eran conocidos con hipertensión arterial y 61,06% con diabetes mellitus. En 24 (21%) pacientes se realizó ecocardiograma y 14 tenían dilatación auricular, con una media de 44 ± 8 mm, y 11 de éstos tenían estenosis mitral. La media de frecuencia cardiaca era 92 ± 18 latidos/min. El ictus isquémico se presentó como debut en 52,21% y de éstos solo 7,08% se conocían portadores de FA. Entre los portadores conocidos de FA 7,08% recibían anticoagulación con acenocumarol. No se encontraron pacientes en tratamiento con otros anticoagulantes. Conclusión: el 22,12% de los pacientes con ACV isquémico estaban diagnosticados con FA. Aproximadamente, un tercio de los pacientes con FA bajo el régimen de anticoagulación no alcanzaron rangos terapéuticos ni una frecuencia cardiaca controlada.

Introduction: It has been shown that one in three ischemic cerebrovascular accidents (CVA) is a consequence of unknown and, therefore, untreated atrial fibrillation (AF). That is why timely diagnosis and treatment of AF is of vital importance since ischemic stroke is a frequent reason for hospital admission. Objectives: To determine the clinical characteristics of patients with ischemic stroke and AF hospitalized at Hospital XX, during 2021 and 2022. Methodology: An observational, descriptive, cross-sectional, retrospective study was carried out. Male and female adult patients, with AF and ischemic stroke confirmed by electrocardiogram and tomography were included. The variables were obtained from the clinical records. The research study was approved by the ethics committee of the National University of Itapúa. Results: One hundred thirteen patients were studied. The mean age was 69 ± 10 years, and 54.87% (62) were men. Among the risk factors, 96.46% were known to have arterial hypertension, and 61.06% were known to have diabetes mellitus. An echocardiogram was performed in 24 (21%) patients, 14 had atrial dilation, with a mean of 44 ± 8 mm, and 11 of these had mitral stenosis. The mean heart rate was 92 ± 18 beats/min. Ischemic stroke occurred as a debut in 52.21% and of these, only 7.08% were known to have AF. Among known AF carriers, 7.08% received anticoagulation with acenocoumarol. No patients were found being treated with other anticoagulants. Conclusion: AF was diagnosed in 22.12% of patients with ischemic stroke. Approximately one-third of AF patients on anticoagulation regimens did not achieve therapeutic ranges or a controlled heart rate.