Periovulatory anticoagulant therapy enhances embryo recovery rates in superovulated mares.

Although protocols for superovulation have been described in horses, this technique has been discouraged due to the low embryo recovery rates in superovulated mares. The reason for these poor results is poorly understood, but the formation of a blood clot in the ovulation fossa following ovulations has been hypothesized. Therefore, this study aimed to assess the safety and effect of periovulatory anticoagulant therapy on embryo recovery of superovulated mares. In experiment 1, five mares were assigned to receive five anticoagulant treatments in a crossover design: intravenous injections of 150 (H1), 300 (H2), 400 (H3), 450 (H4), 600 (H5) IU/kg of unfractionated heparin (UFH, heparin sodium); and had blood samples sequentially collected for up to 48 h post-treatment to test Prothrombin (PT) and activated partial thromboplastin time (aPTT). In experiment 2, four mares were treated in a crossover design with intravenous injection of 450 IU/kg of UFH and 1 mg/kg of low molecular weight heparin (LMWH, enoxaparin) and had blood collected as previously for analysis of plasma anti-Xa activity. In experiment 3, eleven mares had four cycles randomly assigned to four groups. In the control group, mares did not receive any treatment. In contrast, in groups G1, G2, and G3, mares were superovulated with equine pituitary extract and treated 34 h after the induction of ovulation with a placebo (NaCl 0.9 %, G1), 450 IU/kg of UFH (G2), or 1 mg/kg of LMWH. Mares in all groups had ovulation induced with hCG plus histrelin acetate and were bred with fresh semen from one stallion. Embryo flushing was performed nine days post-ovulation. In experiment 1, only mares in groups H4 and H5 had increased aPTT and PT for up to 12 h, and in all groups, aPTT and PT values returned to baselines at 24 h post-treatment. In experiment 2, plasma anti-Xa activity was increased by both therapies for up to 12 h after treatment and was at baseline levels 24 h post-treatment. In experiment 3, periovulatory therapy with anticoagulants increased embryo recovery rates per cycle (G2, 250 %; G3, 260 %) compared to control-assigned cycles (60 %; P < 0.05), whereas G1-assigned cycles (160 %) had intermediate embryo recovery. In conclusion, periovulatory anticoagulant therapies may be an alternative to improve embryo recovery in superovulated mares.

Anticoagulation strategy for patients presenting with ischemic strokes while using a direct oral anticoagulant: A systematic review and meta-analysis.

BACKGROUND: While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7-2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. METHODS: Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. RESULTS: Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43-0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25-0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30-0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06-3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. CONCLUSION: Post-stroke adjustments to anticoagulation therapy-whether altering the drug or its dosage-do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population.

Trends in the Diagnosis of Pediatric Venous Thromboembolism and Arterial Ischemic Stroke during the COVID-19 Pandemic: An Administrative Database Study.

OBJECTIVE: To investigate trends in the diagnosis of venous thromboembolism (VTE) and arterial ischemic stroke (AIS), and examine the use of pharmacological thromboprophylaxis during the COVID-19 pandemic. STUDY DESIGN: This retrospective cohort study used the Pediatric Health Information Systems database to investigate patients admitted to a participating hospital between January 1, 2018, and December 31, 2021. International Classification of Diseases, 10th edition codes were used to identify VTE, AIS, and COVID-19. Pharmacy billing codes were used to investigate pharmacological thromboprophylaxis use. RESULTS: 1 759 701 unique patients underwent 2 234 135 inpatient admissions. Rate of VTE increased from 84 cases per 10 000 admissions in 2018-2019 to 108 cases per 10 000 admissions in 2020-2021, representing a 28.6% increase (P < .001). In contrast, the rate of AIS remained stable through the study period. When compared with 2018-2019, children diagnosed with VTE during 2020-2021 had longer hospitalizations and were more likely to be admitted to the intensive care unit. When analysis was limited to 2020-2021, a diagnosis code of COVID-19 was associated with a 1.35-fold (95% CI: 1.24-1.45) increase in the odds of VTE diagnosis, but not AIS. Use of pharmacologic thromboprophylaxis increased from 1.5% of hospitalizations in 2018-2019 to 3.0% of hospitalizations in 2020-2021 (P < .001). When evaluating thromboprophylaxis during 2020-2021, a diagnosis code for COVID-19 was associated with an 11-fold (95% CI: 10.86-11.49; P < .001) increase in the utilization of pharmacological thromboprophylaxis. CONCLUSIONS: This study found an increase in the rate of VTE among hospitalized children during the pandemic. A diagnosis of COVID-19 was associated with a modest increase in odds of VTE diagnosis, which occurred despite increased use of pharmacological thromboprophylaxis.

Xylan from Dinizia excelsa: Chemical characterization and biological activities.

Dinizia Excelsa is an Amazonian tree with a wide range of applications as a raw material in the industry. The objective of this study was to extract, characterize, and evaluate the biological activities of xylan extracted from Dinizia excelsa wood. The xylan was obtained in five stages, including delignification, precipitation, purification, and freeze-drying. The physicochemical analysis of xylan included the determination of monosaccharides, elemental composition, FTIR analysis, 2D nuclear magnetic resonance spectroscopy, and the determination of molecular weight. Xylan had an extraction yield of 28.44% and an elemental composition of 35.03% carbon, 5.65% hydrogen, and 59.32% oxygen. FTIR analysis revealed similarities between Dinizia excelsa xylan and commercial xylan. 2D NMR analysis confirmed the presence of characteristic xylan groups. Furthermore, xylan has a low molecular weight. In vitro cytotoxicity tests demonstrated low toxicity, indicating its potential for biological applications. Immunomodulatory activity assays revealed that xylan stimulated cell proliferation and the production of anti-inflammatory cytokines. The anticoagulant activity of xylan was low compared to heparin. The antioxidant activity of xylan was weaker compared to ascorbic acid and butylated hydroxytoluene (BHT). These results indicate that xylan from Dinizia excelsa has potential for several biomedical applications due to its immunomodulatory and anticoagulant properties.

Antiplatelet, Anticoagulant, and Fibrinolytic Activity of Orchids: A Review.

Thrombosis is the occlusion of a blood vessel and is responsible for the highest number of deaths worldwide. Its treatment comprises the use of anticoagulants, antiplatelets, and thrombolytics. Although many antithrombotic drugs are currently available, none is completely effective and safe. Plants are a valuable source of compounds with antithrombotic properties. Some orchid species have been used in traditional medicine for their antithrombotic properties. This review informs about the contribution of orchids in this field and the studies that have validated their properties.

Neurovascular complications of antiphospholipid syndrome: a narrative review.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy complications, and other nonthrombotic manifestations in the presence of antiphospholipid antibodies. Neurovascular complications, including ischemic stroke, cerebral venous thrombosis and cognitive impairment, pose significant challenges in management. OBJECTIVE: To comprehensively review relevant and updated clinical aspects of neurovascular manifestations of APS. METHODS: We conducted a narrative review using the PubMed, EMBASE, and Cochrane Library databases with medical terms related to APS and its neurovascular manifestations. English-language studies, published between January 1, 2015, and March 2024, were included. Key publications outside this timeframe were also considered. Studies with higher levels of evidence, such as randomized controlled trials and meta-analyses, were prioritized for inclusion. RESULTS: Stroke is a prevalent complication in APS, with arterial thrombosis being a predominant mechanism. Despite recent trials, direct oral anticoagulants (DOACs) have not shown superiority over vitamin K antagonists (VKAs) for secondary prevention in this population. Cerebral venous thrombosis (CVT), although rare, can also occur in APS, and while DOACs have shown promise as a treatment in a general population, caution is warranted due to potential harm. Cognitive impairment affects a considerable proportion of APS patients, with thrombotic and nonthrombotic mechanisms contributing to its pathophysiology. Future research should focus on optimal management strategies for cognitive impairment and the efficacy of anticoagulation and immunosuppression. CONCLUSION: Understanding the complex interplay of neurovascular manifestations in APS is essential for guiding clinical decisions and improving patient outcomes. Despite advancements, some challenges remain in establishing effective preventive and treatment measures, highlighting the need for further research in this field.

ANTECEDENTES: A síndrome antifosfolipídeo (SAF) é uma doença autoimune sistêmica caracterizada por trombose, complicações na gravidez e outras manifestações não trombóticas na presença de anticorpos antifosfolipídicos. Complicações neurovasculares, incluindo acidente vascular cerebral isquêmico, trombose venosa cerebral (TVC) e comprometimento cognitivo, representam desafios significativos no manejo. OBJETIVO: Revisar de forma abrangente e atualizada os aspectos clínicos relevantes das manifestações neurovasculares da SAF. MéTODOS: Foi realizada uma busca nas bases de dados PubMed, EMBASE e Cochrane, utilizando termos médicos relacionados à SAF e suas manifestações neurovasculares. Estudos em inglês publicados entre 1° de janeiro de 2015 e março de 2024 foram incluídos. Publicações relevantes fora deste período também foram consideradas. Estudos com níveis mais elevados de evidência, como ensaios clínicos randomizados e metanálises, foram priorizados para inclusão. RESULTADOS: O acidente vascular cerebral é uma complicação prevalente na SAF, com a trombose arterial sendo um mecanismo predominante. Apesar de ensaios recentes, os anticoagulantes orais diretos (ACODs) não demonstraram superioridade sobre os antagonistas da vitamina K (AVKs) para a prevenção secundária nesse grupo. A trombose venosa cerebral (TVC), embora rara, também pode ocorrer na SAF, e embora os ACODs tenham mostrado promessa em seu tratamento na população geral, deve-se ter cautela devido ao possível dano. O comprometimento cognitivo afeta uma proporção considerável dos pacientes com SAF, com mecanismos trombóticos e não trombóticos contribuindo para sua fisiopatologia. Pesquisas futuras devem se concentrar em melhores estratégias de manejo para o comprometimento cognitivo e na eficácia da anticoagulação e imunossupressão. CONCLUSãO: Compreender a complexa interação das manifestações neurovasculares na SAF é essencial para orientar decisões clínicas e melhorar os resultados dos pacientes. Apesar dos avanços, alguns desafios permanecem no estabelecimento de medidas preventivas e terapêuticas eficazes, destacando a necessidade de mais pesquisas nesse campo.

[Guide to the treatment of paediatric strokes. Iberoamerican Academy of Pediatric Neurology]. / Guía de tratamiento del accidente cerebrovascular. Academia Iberoamericana de Neurología Pediátrica.

A paediatric stroke is a rare entity that can occur at any age. It may be arterial or venous, ischemic or haemorrhagic, and may occur in the neonatal or paediatric stage of life, as well as in adolescence. Prompt diagnosis means that adequate treatment can be administered and prevents recurrence, minimising the percentage of sequelae. This guide aimed to analyse, prepare and classify the literature currently available in order to determine the best recommendations on the treatment of strokes in paediatric patients. In each section, we attempted to answer the following questions: when should we think in terms of a stroke and thrombosis of the cerebral venous sinuses in a newborn or paediatric patient? What are the recommended complementary studies? Is treatment indicated? What are the recommended treatments? This guide was prepared based on the opinion of experts in the field, in order to determine how the recommendations were assessed according to the 2011 Oxford Levels of Evidence. Finally, the guidelines were reviewed by the scientific committee of the Iberoamerican Academy of Pediatric Neurology for subsequent dissemination.

TITLE: Guía de tratamiento del accidente cerebrovascular. Academia Iberoamericana de Neurología Pediátrica.Resumen. El accidente cerebrovascular es una entidad poco frecuente que puede ocurrir en todos los períodos de la pediatría. Puede ser arterial o venoso, isquémico o hemorrágico, y de presentación en el período neonatal o pediátrico y en la adolescencia. Su diagnóstico temprano permitirá iniciar un tratamiento adecuado y evitar la recurrencia, y minimizará el porcentaje de secuelas. Esta guía tuvo como objetivo analizar, preparar y calificar la bibliografía actual para determinar las mejores recomendaciones sobre el tratamiento del accidente cerebrovascular en pediatría. En cada apartado se intentó responder a las siguientes preguntas: ¿Cuándo debemos pensar en un accidente cerebrovascular y en una trombosis de senos venosos cerebrales en un recién nacido o paciente pediátrico? ¿Cuáles son los estudios complementarios recomendados? ¿Se indica tratamiento? ¿Cuáles son los tratamientos recomendados? Su confección se basó en la opinión de expertos en el campo para poder determinar la calificación de las recomendaciones utilizando los niveles de evidencia de Oxford de 2011. Finalmente, la guía fue sometida a la revisión por parte del comité científico de la Academia Iberoamericana de Neurología Pediátrica para su posterior difusión.

DOACs versus aspirin for secondary prevention of stroke after ESUS: an updated systematic review and meta-analysis of randomized clinical trials

BACKGROUND: Embolic stroke of undetermined source (ESUS) is a nonlacunar ischemic stroke with no clear cause, having a 4%-5% annual recurrence rate. The potential benefits of direct oral anticoagulants (DOACs) relative to aspirin in patients with ESUS remain unclear. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to determine the efficacy of the DOACs in secondary prevention for patients with ESUS compared with aspirin. METHODS: MEDLINE, Embase, Cochrane, and ClinicalTrias.gov were searched for RCTs comparing DOACs versus aspirin for secondary stroke prevention after ESUS. We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review (PRISMA) and Cochrane guidelines. Statistical analysis was performed using R software 4.3.2. A random-effects model was employed to measure mean differences and hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: We included 4 RCTs comprising 13,970 patients. The median age was 67 years (IQR 65.5-68.2), 61% were male, 76% had hypertension, and 51% had diabetes. DOACs were administered to 50% of the participants. No significant difference was found between groups for stroke recurrence [RR 0.95 (95% CI 0.8-1.11) p=0.52; I2=0%]. Death from any cause [HR 1.11 (95% CI 0.87-1.42) p=0.38; I2=0%], cardiovascular death [HR 1.08 (95% CI 0.61-1.94) p=0.77; I2=18%] and myocardial infarction [HR 0.92 (95% CI 0.54-1.54) p=0.76; I2=16%] were also similar between groups. However, there was a significant increase in clinically relevant non-major bleeding for patients treated with DOACs [HR 1.53 (95% CI 1.22-1.92) p<0.001; I2=9%]. CONCLUSION: In patients with ESUS, DOACs were not superior to aspirin for the secondary prevention of stroke. However, there was a significant increase in clinically relevant non-major bleeding among patients treated with DOACs. These findings suggest that aspirin remains a viable option for secondary prevention in ESUS patients.

Lack of Anticoagulant Use in Patients with Atrial Fibrillation and Increased Risk of Thromboembolic Events According to Sex: Insights from a Multicentric Brazilian Study. / 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.

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.

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.

Rivaroxaban Versus Warfarina ou Apixaban em pacientes diabéticos com fibrilação atrial não valvular: uma revisão sistemática e meta-análise / Rivaroxaban Versus Warfarin or Apixaban in diabetic patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

INTRODUÇÃO: Pacientes com fibrilação atrial não valvular (FANV) e diabetes mellitus (DM) têm até 70% mais risco de AVC do que pacientes com FANV e sem diabetes. Além disso, estudos ainda discutem se rivaroxaban e apixaban são alternativas ao tratamento tradicional com warfarina em pacientes com DM e FANV. Esta meta-análise, portanto, compara a eficácia e segurança de rivaroxaban versus warfarina ou apixaban na redução de AVC e de sangramentos maiores nesse subgrupo. MÉTODOS: Bases de dados Cochrane, PubMed, Scopus e Web of Science foram pesquisadas por estudos clínicos randomizado e de coorte que comparam rivaroxaban com warfarina ou com apixaban em pacientes com DM e FANV. Usamos um modelo de efeitos aleatórios para calcular hazard ratio (HR) e risk ratio (RR), com 95% de intervalo de confiança (CI), e a heterogeneidade foi analisada com o teste I². Aestatística foi realizada pelo software RStudio versão 4.4.1. RESULTADOS: Nos 13 estudos selecionados de pacientes com DM e FANV, um total de 538.213 pacientes foram incluídos: 238.798 receberam rivaroxaban, 212.839, warfarina e 86.576, apixaban. Rivaroxaban apresentou desfecho favorável para redução de AVC (HR 0.8413; 95% CI 0.7703-0.9187; P < 0.001; I² = 68%), AVC hemorrágico (HR 0.5619; 95% CI 0.4584-0.6888; P< 0.001; I² = 0%), hemorragia intracraniana (HR 0.6440; 95% CI 0.5442-0.7621; P< 0.001; I² = 0%), mas não para gastrointestinal (HR 1.1396; 95% CI 1.0290-1.2621; P = 0.012; I² = 0%) quando comparado a warfarina. Apixaban apresentou desfechos favoráveis em redução de AVC (HR 0.88; 95% CI 0.8025-0.9651; P = 0.007; I² = 0%) e de sangramentos maiores (HR 0.5916; 95% CI 0.5383-0.6501; P< 0.001; I² = 59%), comparado a rivaroxaban. CONCLUSÃO: Essa meta-análise sugere que o uso de rivaroxaban é mais eficaz e seguro quanto ao risco de AVC e hemorragias intracranianas comparado à warfarina, mas aumenta o risco de sangramento gastrointestinal nesses pacientes. Apixaban, por sua vez, mostrou ser mais eficaz que o rivaroxaban na redução de AVC e sangramentos maiores. Essas evidências, pois, orientam o manejo de anticoagulantes em pacientes com DM e FANV.

Validation of the HAS-BLED scale for the assessment of bleeding risk in patients on anticoagulation therapy with a diagnosis of venous thromboembolic disease.

Background: Several models have been developed to assess bleeding risk in patients with venous thromboembolism, such as HAS-BLED, but their external validity has not been adequately assessed. Objective: The objective of the study was to evaluate the discriminative ability and calibration of the HAS-BLED scale for predicting 1-month bleeding risk in patient's anticoagulated for venous thromboembolism. Materials and Methods: External validation study of a prediction model based on a retrospective cohort of patients with venous thromboembolism treated between November 2019 and January 2022. Calibration of the HAS-BLED scale was evaluated using the Hosmer-Lemeshow test and the ratio of observed to expect events within each risk category. Discriminatory ability was assessed using the area under the curve (AUC) of a receiver operating characteristic curve. Results: We included 735 patients (median age 64 years, female sex 55.2%), pulmonary embolism was diagnosed in most patients (60.7%), and 4.9% presented bleeding events. Regarding calibration, the HAS-BLED scale systematically underestimates the risk both in the general population (ROE 3.76, p < 0.001) and in cancer patients (ROE 4.16). The Hosmer-Lemeshow test rejected the hypothesis of adequate calibration (p < 0.001). Discriminatory ability was limited both in the general population (AUC = 0.57, 95% confidence interval [CI]: 0.48-0.66) and in the subgroup with active cancer (AUC = 0.53, 95% CI: 0.36-0.69). Conclusion: The HAS-BLED scale in patients with venous thromboembolism underestimates the risk of bleeding at 1 month and has a low ability to discriminate high-risk patients. Cautious interpretation of the scale is recommended until additional evidence is available.

Anticoagulant-Related Nephropathy as a Cause of Early Graft Dysfunction.

Anticoagulant-related nephropathy is an increasingly recognized entity, characterized by the presence of hematuria in the context of a supratherapeutic international normalized ratio with the development of secondary acute kidney injury, which may require renal replacement therapy and may progress to chronic kidney disease. We present the case of a 63-year-old patient who started anticoagulant therapy with acenocoumarol 2 months after her kidney transplant and presented with graft dysfunction concomitant to a supratherapeutic international normalized ratio.

Anticoagulant Effect of Snow mountain garlic: In Vitro Evaluation of Aqueous Extract.

Snow mountain garlic is traditionally eaten by Himalayan locals for its medicinal properties. Although different species of the genus Allium are known to have other biological effects, such as antiplatelet and antithrombotic activities, little is known about the anticoagulant effect of Snow mountain garlic, a member of the genus Allium. Therefore, the present study examined the in vitro anticoagulant effect of the aqueous extract, the lyophilized aqueous extract, and the isoflavone extract from the lyophilized aqueous extract of Snow mountain garlic in samples from 50 human blood donors. Compared to the control, concentrations of 25, 12.5, and 6.25 mg/100 µL lengthened the clotting times of prothrombin, and concentrations of 25 and 12.5 mg/100 µL lengthened the activated partial thromboplastin time (p ˂ 0.05). The isoflavone extract from the lyophilized aqueous extract containing isoflavones, organosulfur compounds, a polyphenol, and a steroid glycoside showed a significant effect (p ˂ 0.05) on the prothrombin time and the activated partial thromboplastin time at a dose of 20 µL (volume) compared to the control. The results regarding the use of Snow mountain garlic as a preventive measure and aid in treating thromboembolic disease are promising.

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

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.

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.

Effects of anticoagulants time storage on stable isotope values of crocodilians' blood tissues.

Rapid coagulation of reptile blood often hinders its use in studies in remote and difficult-to-access areas, necessitating chemical preservation. Therefore, understanding the potential effects of anticoagulants on the isotopic compositions of blood is essential to avoid issues in interpreting the results for ecological studies. In this study we aimed to verify whether the storage time of the blood tissue in anticoagulants can influence its isotopic compositions of the broad-snouted caiman (Caiman latirostris), an ectothermic top predator from eastern South America. Blood samples were obtained from ten adult females of C. latirostris from a commercial breeding facility in 2015. Samples were stored in vials containing ethylenediaminetetraacetic acid (EDTA) and sodium heparin (SH) and centrifuged after 2 and 8 h to separate red blood cells and plasma. No effect of time was found on the δ13C and δ15N of whole blood, plasma, and red blood cells in contact with the two types of anticoagulants, EDTA and SH. The findings have practical implications for researchers in this field, as they suggest that anticoagulants can be used effectively for at least eight hours under refrigeration.

Health-related quality of life with rivaroxaban plus aspirin vs. aspirin alone in chronic stable cardiovascular disease: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial

AIMS: This study aimed to compare the effects of the combination of rivaroxaban and aspirin with aspirin alone on health-related quality of life in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. METHODS and results: Health-related quality of life assessed using the EQ-5D-3L. The treatment effects on health utility and EQ visual analogue scale (EQ VAS) scores were compared between rivaroxaban plus aspirin and aspirin alone in terms of adjusted mean difference in change from baseline and odds ratio of having deterioration events. Nine thousand forty-nine (98.9%) and 6916 (75.5%) completed the EQ-5D-3L at baseline and at final visit, respectively. Nine thousand twenty-eight (98.9%) and 6887 (76.3%) completed the EQ-5D-3L at baseline and final visit, respectively. Mean (standard deviation) health utility and EQ VAS scores at baseline were 0.871 (0.141) and 76.0 (15.3), respectively, for the rivaroxaban plus aspirin group, compared with 0.873 (0.139) and 75.8 (15.1) for the aspirin group. Adjusted mean difference in change from baseline utility was -0.002 [95% confidence interval (CI), -0.006, 0.002, P = 0.30] between the combination therapy group and the aspirin group. The odds ratio (95% CI) of experiencing deterioration in health utility was 1.01 (95% CI, 0.93, 1.10, P = 0.81) between the two groups. Adjusted mean difference in change from baseline EQ VAS was 0.02 (95% CI, -0.43, 0.47, P = 0.93) between the two groups. CONCLUSION: This analysis of the COMPASS trial demonstrated that the quality of life of patients was similar between the rivaroxaban plus aspirin group and the aspirin alone group. REGISTRATION: Trial registration number: ClinicalTrials.gov number (NCT01776424). Trial protocol and statistical analysis plan: https://www.nejm.org/doi/full/10.1056/NEJMoa1709118#APPNEJMoa1709118PRO.

Incidence of venous thromboembolism and adequacy of thromboprophylaxis in 2380 acutely-ill hospitalized patients: Results from the PROFMiG cohort study.

INTRODUCTION: Hospital-acquired venous thromboembolism (VTE) is a major cause of preventable deaths. Incidence of VTE and adequacy of thromboprophylaxis have rarely been reported in low-resourced countries. The aim of this study was to estimate the incidence of VTE and to evaluate the adequacy of thromboprophylaxis in acutely-ill medical hospitalized patients. METHODS: The PROFMiG is a prospective cohort study conducted in Brazil. We consecutively enrolled adult (> 18 years) acutely-ill hospitalized medical patients at admission. Risk assessment for VTE was evaluated by the IMPROVE7 (International Medical Prevention Registry on Venous Thromboembolism). Outcomes were death and VTE events during hospital stay up to 90 days after discharge. All VTE and death events were adjudicated. We also evaluated pulmonary embolism-related death and adequacy of thromboprophylaxis. VTE incidence was estimated by competing risk methods. RESULTS: A total of 2380 participants was included. Median age was 70 years, 56.1 % women, median length of hospital stay was 10 days. A total of 2052 (86.3 %) patients were classified as low-risk for VTE, 30 (1.3 %) patients had objectively confirmed VTE, and 1449 (60.8 %) received inadequate thromboprophylaxis. The overall mortality rate was 14.0 %. Cumulative incidence of VTE was 2.0 % (95 % confidence interval 0.9 %-3.8 %) at 130 days after admission when considering death as competing risk. CONCLUSION: The cumulative incidence of VTE in this cohort corroborates with that reported in high-resourced countries. Despite recommendation, thromboprophylaxis was mostly inadequate. We suggest the adoption of competing risk analysis to estimate the cumulative incidence of VTE in hospitalized patients.

Trombosis de seno transverso: Relato de un caso / Transverse sinus thrombosis: Case report

Introducción: Se entiende por trombosis venosa cerebral a la oclusión de algún componente del sistema venoso cerebral secundaria a trombos. Su localización más frecuente es el seno transverso y su síntoma más frecuente es la cefalea. El presente estudio describe el manejo de una trombosis de seno transverso en nuestro servicio. Desarrollo del Caso: Paciente femenino de 32 años que consultó por cefalea hemicraneana derecha de intensidad 10/10, asociada a vómitos y hemiparesia izquierda, de inicio súbito durante un esfuerzo físico. Ingresó hemodinámicamente estable, afebril, sin requerimientos de oxígeno, desorientada, con hemiparesia izquierda. Se realizó tomografía de cerebro, que evidenció hiperdensidad occipital derecha en relación con seno venoso transverso. Se realizó angioresonancia de cerebro, que informó la presencia de trombosis en seno venoso derecho. Ante la necesidad de ini- ciar anticoagulación, se decidió, en conjunto con el servicio de Ginecología, colocar un sistema intrauterino con liberación de levonorgestrel para manejo local de la metrorragia. Inició anticoagulación y presentó mejoría del foco motor, persistiendo con una paresia grado IV de miembro superior izquierdo, que resolvió al tercer día de internación. Luego de 5 días en terapia intensiva y 3 días en Clínica, una vez lograda anticoagulación oral, se le otorgó el alta hospitalaria. Conclusión: Para el diagnóstico es imprescindible los estudios de imágenes que permiten identificar la localización de la trombosis y complicaciones que se pueden presentar. La resonancia es una técnica muy efectiva permite visualizar tanto la localización, extensión, lesiones asociadas en el parénquima y en ocasiones la causa subyacente.

Introduction: Cerebral venous thrombosis is understood as the occlusion of some component of the cerebral venous system secondary to thrombi. Its most common location is the transverse sinus and its most common symptom is headache. This report seeks to describe the management of transverse sinus thrombosis in our service. Case Development: A 32-year-old female patient presented with a right hemicranial headache of 10/10 intensity, associated with vomiting and left hemiparesis, with sudden onset during physical exertion. She was admitted hemodynamically stable, afebrile, without oxygen requirements, disoriented, with left hemiparesis. A brain tomography was performed, which showed right occipital hyperdensity in relation to the transverse venous sinus. Brain angio- resonance was performed, which reported the presence of thrombosis in the right venous sinus. Given the need to start anticoagulation, it was decided, together with the Gynecology service, toplace an intrauterine system with levonorgestrel release for local management of metrorrhagia. He started anticoagulation and showed improvement in the motor focus, persisting with grade IV paresis of the left up- per limb, which resolved on the third day of hospitalization. After 5 days in intensive care and 3 days in the Clinic, after achieving oral anticoagulation, he was discharged from the hospital. Conclusion: For diagnosis, imaging studies are essential, which allow identifying the location of the thrombosis and complications that may occur. Resonance is a very effective technique that allows visualization of the location, extent, associated lesions in the parenchyma and sometimes the underlying cause.

Timing Matters: Ultra-Early and Early versus Late Thromboprophyaxis Following Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Spontaneous intracerebral hemorrhage (ICH) represents a critical and potentially devastating medical event resulting from the rupture of intracerebral vessels. Patients afflicted with ICH face an increased risk of venous thromboembolism (VTE) due to factors such as immobility. However, determining the ideal timing for initiating venous thromboembolism thromboprophylaxis (TP) remains uncertain, as it may carry the potential risk of exacerbating hematoma expansion. Thus, our objective was to ascertain the optimal timing for initiating TP following ICH through a comprehensive systematic review and meta-analysis.This systematic review and meta-analysis were performed following the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines, considering outcomes based on the time of intervention: Ultra early (UEPT) < 24 h, Early (EPT) < 48 h, Late (LPT) > 48 h to perform an analysis on hematoma expansion and mortality.Of 2.777 Hematoma expansion was not more frequent in the 440 patients receiving UEPT/EPT (n = 440) versus 565 receiving LPT (Odds ratio (OR) 0.94 (95% CI; 0.62 to 1.43; I2 = 0%)). Similarly, mortality was not lower in the 293 received UEPT or EPT versus 477 receiving LPT (OR 0.63 (95% CI; 0.39 to 1.0; I2 = 0%).This study, through a systematic review and meta-analysis, conclusively found no difference in intracranial hematoma expansion and/or increased mortality between the use of heparin in the early thromboprophylaxis (< 48 h) group compared to the late thromboprophylaxis (> 48 h) group. Implementing this approach in the management of spontaneous cerebral hemorrhage could facilitate progress towards more optimal care protocols.