Drogas antiagregantes plaquetárias e anticoagulantes em pacientes que se submeterão à cirurgia oral: conduta / Antiagregant platelet and anticoagulant drugs in patients who will submit oral surgery: conduct

Objetivo: Como a frequência de pacientes em uso de anticoagulantes e antiagragantes plaquetários nos consultórios odontológicos é crescente, este trabalho objetivou avaliar através de Revisão de Literatura, qual o melhor manejo desses medicamentos na prática odontológica perioperatória. Metodologia: Trata-se de uma revisão integrativa da literatura, utilizadas as bases de dados Scielo e PubMed. Foram escolhidos os seguintes descritores disponíveis na BVs e PubMed em inglês "Platelet Aggregation Inhibitors", "Oral Surgical Procedures" e "Antigoagulants" no período de 2016 a 2021. Também foram consultados livros e sites de diretrizes do Governo. Foram escolhidos 20 artigos para elaboração da pesquisa. Resultados: doenças cardiovasculares e outras condições clínicas pró-coagulantes tem prevalência crescente e são conhecidos fatores de risco para a ocorrência de fenômenos tromboembólicos graves. A terapia antitrombótica tem papel definido nesses casos. No perioperatorio de cirurgias orais, a decisão por suspender ou manter a terapia deve ser individualizada e pode ser orientada por guidelines. Conclusão: procedimentos orais de baixo risco de sangramento podem ser conduzidos sem a descontinuação da terapia antitrombótica. Cirurgias de moderado a alto risco frequentemente requerem suspensão temporária das medicações para fins de minimizar os riscos de complicações hemorrágicas... (AU)

Objective: As the frequency of patients using anticoagulants and antiplatelet agents in dental offices is increasing, this study aimed to evaluate, through a Literature Review, which is the best management of these medications in dental perioperative practice. Methodology: This is an integrative literature review, being used Scielo and PubMed databases. The following descriptors available in BVs and PubMed "Platelet aggregation inhibitors", "Oral Surgical Procedures" and "Antigoagulants" were used, from 2016 to 2021. In addition, the search was also performed in guideline books and Government websites. Twenty articles were chosen for research elaboration. Results: established cardiovascular disease and other procoagulant clinical conditions have an increasing prevalence, especially among the elderly, and are known risk factors for the occurrence of severe thromboembolic phenomena. Antithrombotic therapy has defined role in these cases. In the perioperative period of oral surgery, the decision to suspend or maintain therapy must be individualized and may be guided by guidelines. Age appears as a clinical criterion in the main ones used. Conclusion: oral procedures with low risk of bleeding can be carried out without discontinuing antithrombotic therapy. Moderate to high-risk surgeries usually require its temporary suspension in order to minimize the risk of bleeding complications... (AU)

Venenos de serpentes do gênero Bothrops: impacto da glicosilação na complexidade dos proteomas e função de toxinas / Bothrops snake venoms: impact of glycosylation on the complexity of proteomes and toxins function

A variabilidade estrutural é uma característica das proteínas de venenos de serpentes, e a glicosilação é uma das principais modificações pós-traducionais que contribui para a diversificação de seus proteomas. Recentes estudos de nosso grupo demonstraram que venenos do gênero Bothrops são marcadamente definidos pelo seu conteúdo de glicoproteínas, e que a maioria das estruturas de N-glicanos dos tipos híbrido e complexo identificados em oito venenos deste gênero contêm unidades de ácido siálico. Em paralelo, em glicoproteínas do veneno de B. cotiara foi identificada a presença de uma estrutura de N-acetilglicosamina bissecada. Assim, com o objetivo de investigar a variação do conteúdo de glicoproteínas, assim como os mecanismos envolvidos na geração dos diferentes venenos de Bothrops, neste estudo foram analisados comparativamente os glicoproteomas de nove venenos do gênero Bothrops (B. atrox, B. cotiara, B. erythromelas, B. fonsecai, B. insularis, B. jararaca, B. jararacussu, B. moojeni e B. neuwiedi). As abordagens glicoproteômicas envolveram cromatografia de afinidade e ensaio de pull-down utilizando, respectivamente, as lectinas SNA (aglutinina de Sambucus nigra) e MAL I (lectina de Maackia amurensis), que mostram afinidade por unidades de ácido siálico nas posições, respectivamente, α2,6 e α2,3; e cromatografia de afinidade com a lectina PHA-E (eritroaglutinina de Phaseolus vulgaris), que reconhece N-acetilglicosamina bissecada. Ainda, eletroforese de proteínas, blot de lectina, e identificação de proteínas por espectrometria de massas foram empregadas para caracterizar os glicoproteomas. As lectinas geraram frações dos venenos enriquecidas de diferentes componentes, onde as principais classes de glicoproteínas identificadas foram metaloprotease, serinoprotease, e L-amino ácido oxidase, além de outras enzimas pouco abundantes nos venenos. Os diferentes conteúdos de proteínas reconhecidas por essas lectinas, com especificidades distintas, ressaltaram novos aspectos da variabilidade dos subproteomas de glicoproteínas desses venenos, dependendo da espécie. Ainda, considerando que metaloproteases e serinoproteases são componentes abundantes nesses venenos e fundamentais no quadro de envenenamento botrópico, e que estas enzimas contêm diversos sítios de glicosilação, o papel das unidades de ácido siálico na atividade proteolítica das mesmas foi avaliado. Assim, a remoção enzimática de ácido siálico (i) alterou o padrão de gelatinólise em zimografia da maioria dos venenos, (ii) diminuiu a atividade proteolítica de alguns venenos sobre o fibrinogênio e a atividade coagulante do plasma humano de todos os venenos, e (iii) alterou o perfil de hidrólise de proteínas plasmáticas pelo veneno de B. jararaca, indicando que este carboidrato pode desempenhar um papel na interação das proteases com seus substratos proteicos. Em contraste, o perfil da atividade amidolítica dos venenos não se alterou após a remoção de ácido siálico e incubação com o substrato Bz-Arg-pNA, indicando que ácido siálico não é essencial em N-glicanos de serinoproteases atuando sobre substratos não proteicos. Em conjunto, esses resultados expandem o conhecimento sobre a variabilidade de proteomas de venenos do gênero Bothrops e apontam a importância das cadeias de carboidratos contendo ácido siálico nas atividades enzimáticas das proteases desses venenos

Structural variability is a feature of snake venom proteins, and glycosylation is one of the main post-translational modifications that contributes to the diversification of venom proteomes. Recent studies by our group have shown that Bothrops venoms are markedly defined by their glycoprotein content, and that most hybrid and complex N-glycan structures identified in eight venoms of this genus contain sialic acid units. In parallel, the presence of a bisected N-acetylglucosamine structure was identified in B. cotiara venom glycoproteins. Thus, with the aim of investigating the variation in the content of glycoproteins, as well as the mechanisms involved in the generation of different Bothrops venoms, in this study the glycoproteomes of nine Bothrops venoms (B. atrox, B. cotiara, B. erythromelas, B. fonsecai, B. insularis, B. jararaca, B. jararacussu, B. moojeni e B. neuwiedi) were comparatively analyzed. The glycoproteomic approaches involved affinity chromatography and pulldown using, respectively, the lectins SNA (Sambucus nigra agglutinin) and MAL I (Maackia amurensis lectin), which show affinity for sialic acid units at positions, respectively, α2,6 and α2,3, and affinity chromatography with PHA-E (Phaseolus vulgaris erythroagglutinin), which recognizes bisected N-acetylglucosamine. In addition, protein electrophoresis, lectin blot, and protein identification by mass spectrometry were employed for glycoproteome characterization. The lectins generated venom fractions enriched with different components, where the main classes of glycoproteins identified were metalloprotease, serine protease, and L-amino acid oxidase, in addition to other low abundant enzymes. The different contents of proteins recognized by these lectins of distinct specificities highlighted new aspects of the variability of the glycoprotein subproteomes of these venoms, depending on the species. Furthermore, considering that metalloproteases and serine proteases are abundant components of these venoms and essential in Bothrops envenomation, and that these enzymes contain several glycosylation sites, the role of sialic acid units in their proteolytic activities was evaluated. Thus, enzymatic removal of sialic acid (i) altered the pattern of gelatinolysis in zymography of most venoms, (ii) decreased the proteolytic activity of some venoms on fibrinogen and the clotting activity of human plasma of all venoms, and (iii) altered the hydrolysis profile of plasma proteins by B. jararaca venom, indicating that this carbohydrate may play a role in the interaction of proteases with their protein substrates. In contrast, the profile of amidolytic activity of the venoms did not change after removal of sialic acid and incubation with the substrate Bz-Arg-pNA, indicating that sialic acid is not essential in N-glycans of serine proteases acting on small substrates. Together, these results expand the knowledge about the variability of proteomes of Bothrops venoms and point to the importance of carbohydrate chains containing sialic acid in the enzymatic activities of venom proteases

Biomarcadores cardiacos de aterotrombosis y su implicación en la estimación del riesgo de enfermedad cardiovascular / Cardiac biomarkers of atherothrombosis and their implication in estimating the risk of cardiovascular disease

Introducción: Las innovadoras estrategias para la estimación del riesgo cardiovascular que apelan al empleo de biomarcadores cardiacos de aterotrombosis, han evidenciado ser superiores en la estratificación del riesgo cardiovascular por encima de aquellas predicciones basadas exclusivamente en la evaluación de factores de riesgo tradicionales de manera aislada. Se realizó una revisión bibliográfica, análisis y categorización de diferentes artículos en las bases de datos Cumed, Lilacs, SciELO, Medline, los términos clave para la búsqueda fueron: homocisteína, lipoproteína (a) y riesgo cardiovascular, en español, inglés y portugués. Se consideraron artículos originales, de revisión, incluyendo revisiones sistemáticas y metaanálisis posteriores al año 2000. Objetivo: Analizar los biomarcadores cardiacos de aterotrombosis, involucrados en el desarrollo de la enfermedad cardiovascular aterosclerótica y sus complicaciones trombóticas. Desarrollo: La evidencia acumulada sustenta que biomarcadores cardiacos como la hiperhomocisteinemia, la hiperlipoproteinemia (a), el incremento de los niveles plasmáticos del fibrinógeno, el factor VII coagulante, el inhibidor del activador tisular del plasminógeno tipo 1 y la proteína C reactiva, son herramientas de gran utilidad para estratificar el riesgo cardiovascular en individuos de riesgo intermedio, o con riesgo inusual o de riesgo indefinido, esencialmente en el ámbito de la prevención primaria y secundaria de la enfermedad cardiovascular . Conclusiones: La identificación de biomarcadores emergentes de aterotrombosis predictivos adicionales, es trascendental para una prevención y terapéutica más eficaz de la enfermedad cardiovascular aterosclerótica(AU)

Introduction: Innovative cardiovascular risk estimation strategies that use cardiac biomarkers of atherothrombosis have been shown to be superior in cardiovascular risk stratification that those predictions based exclusively on the evaluation of traditional risk factors in isolation. A bibliographic review, analysis and categorization of different articles was performed in the databases Cumed, Lilacs, Scielo, Medline, the key terms for the search were: "homocysteine", "lipoprotein (a)" and "cardiovascular risk", in Spanish, English and Portuguese languages. Original review articles were considered, including systematic reviews and published meta-analyzes after 2000. Objective: To analyze some of the cardiac biomarkers of atherothrombosis that may be involved in the development of atherosclerotic cardiovascular disease and its thrombotic complications. Development: Accumulated evidence supports that cardiac biomarkers such as: hyperhomocysteinemia, hyperlipoproteinemia (a), increased plasma fibrinogen levels, coagulant factor VII, Plasminogen Tissue Activator Inhibitor type 1 and C-reactive protein are tools of Very useful for stratifying cardiovascular risk in those individuals with intermediate risk, or with unusual or undefined risk, essentially in the field of primary and secondary prevention of cardiovascular disease. Conclusions: The identification of additional predictive emergent atherothrombosis biomarkers is crucial for a more effective prevention and therapy of atherosclerotic cardiovascular disease(AU)

Profilaxia da trombose venosa profunda em cirurgia bariátrica: estudo comparativo com doses diferentes de heparina de baixo peso molecular / Deep venous thrombosis prevention in bariatric surgery: comparative study of different doses of low weight molecular heparin

Contexto: A cirurgia bariátrica é considerada a melhor opção para o tratamento da obesidade, cujos pacientes são considerados de alto risco para fenômenos tromboembólicos. Objetivos: Comparar o uso de doses diferentes de heparina de baixo peso molecular (HBPM) na profilaxia da trombose venosa profunda (TVP) em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, alteração na dosagem do fator anti-Xa e sangramento pré ou pós-operatório. Métodos: Estudo comparativo transversal em pacientes submetidos à cirurgia bariátrica distribuídos em dois grupos, que receberam doses de HBPM de 40 mg (grupo controle, GC) e 80 mg (grupo de estudo, GE). Foram avaliados por ultrassonografia vascular e dosagem de KPTT, TAP, plaquetas e fator anti-Xa. Resultados: Foram avaliados 60 pacientes, sendo 34 no GC e 26 no GE. Foi observada diferença significativa somente no peso (p = 0,003) e índice de massa corporal (p = 0,018) no GE em relação ao GC. Não houve diferença na dosagem de KPTT, TAP, plaquetas e fator anti-Xa entre os grupos. Não foram detectados TVP ou sangramentos significativos em ambos os grupos. Conclusões: Não houve diferença estatisticamente significativa na utilização de doses maiores de HBPM na profilaxia da TVP em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, dosagem do fator anti-Xa e sangramento pré ou pós-operatório

Background: Bariatric surgery is considered the best treatment option for patients with obesity who are classed as high risk for thromboembolic events. Objectives: To compare two different doses of low weight molecular heparin (LWMH) for prevention of deep venous thrombosis (DVT) in candidates for bariatric surgery, in terms of DVT risk, abnormal anti-Xa levels, and preoperative and/or postoperative bleeding. Methods: A cross-sectional comparative study of bariatric surgery patients divided into two groups given different doses of LWMH; 40 mg of LWMH (control group, CG) and 80 mg of LWMH (study group, SG), both evaluated by vascular ultrasonography (VU) and according to the results of PTT, PT, platelets, and anti-Xa factor assays. Results: Sixty patients were evaluated, 34 in the CG and 26 in the SG. The only significant differences between the patients in the SG and the CG were weight (p = 0.003) and body mass index (p = 0.018). There were no differences between the groups in PTT, PT, platelets, or anti-Xa factor levels. There was no DVT or significant bleeding in either group. Conclusions: There were no statistical differences when higher doses of LWMH were used for prevention of DVT in bariatric surgery patients, in terms of DVT risk, anti-Xa factor levels, or preoperative and postoperative bleeding

Era of Bloodless Surgery: Spotlights on Hemostasic Materials and Techniques / 한양의대학술지

Ever since mankind has had blood, efforts to stop bleeding have never ceased and so numerous methods for hemostasis have been developed. In recent decades, minimally invasive surgical techniques have led patients to less-bleeding surgery but, hemostatic agents, devices and techniques still play an important role in medical side. A number of hemostatic agents and devices have been developed and they can be classified by their mechanism of action. That classification of the coagulants includes mechanisms with physical, caustic, bio-physical, biologic actions. Hemostatic devices are divided into categories such as dressings, glue, clips, electrocoagulations and so on. Based on the concept of minimally invasive surgical procedures, variously developed surgical techniques are divided by the number of ports used and auxiliary instruments. However, there are advantages and disadvantages to each of the hemostatic agents and minimally invasive methods, and the belief in the classical method also prevents the application of new hemostatic methods. The knowledge and understanding of the benefits and costs of these newly developed hemostatic methods will make it easier for medical personnel to manage patient's blood.

Comparación de la detección foto óptica vs. electromecánica del coágulo / Comparison of mechanical vs. optical clot detection / Comparação da detecção foto-óptica vs. eletromecânica do coágulo

El objetivo de este estudio fue determinar si la detección foto óptica del coágulo es equivalente a la detección electromecánica al realizar el tiempo de protrombina (TP), el tiempo de tromboplastina parcial activado (APTT) y el dosaje de fibrinógeno (FBG). Se estudiaron 258 pacientes consecutivos que concurrieron al laboratorio para realizar estudios de hemostasia. Se utilizaron tres coagulómetros: ACL TOP (foto-óptico) y STArt y Destiny plus como detección electro mecánica. EL TP, APTT y FBG fueron realizados en todos los equipos antes de transcurridas tres horas de la toma de la muestra. Se obtuvo una buena correlación entre los resultados obtenidos con ambos métodos de detección TP (%): (ACL TOP vs. STArt R=0,989; ACL TOP vs. Destiny plus R=0,988), APTT: (ACL TOP vs. STArt R=0,938; ACL TOP vs. Destiny Plus R=0,989), y FBG (ACL TOP vs. STArt R=0,97; ACL TOP vs. Destiny Plus R=0,984). La diferencia de los resultados entre plataformas son menores al error total permitido establecido por los criterios de CLIA (ETa TP y APTT =15% y FBG 20%) en el 95% de las muestras. En los tres coagulómetros evaluados, correctamente mantenidos y calibrados, la detección foto-óptica arrojó resultados equivalentes a la detección electromecánica.

The aim of this study was to determine whether two distinct methodologies based on optical or mechanical clot detection are comparable. Prothrombin time (PT), activated partial thromboplastine time (APTT) and fibrinogen results obtained with mechanical method using two different coagulometers are compared with those obtained by photo optical method within three hours of blood collection. The statistical analysis demonstrated an excellent correlation between optical or mechanical platform for TP, APTT and FBG. TP (%) showed (ACL TOP vs. STArt R=0.989; ACL TOP vs. Destiny Plus R=0.988), APTT: (ACL TOP vs. STArt R=0.938; ACL TOP vs. Destiny Plus R=0.989) y FBG (ACL TOP vs. STArt R=0.97; ACL TOP vs. Destiny Plus 0.984). The differences between optical or mechanical clot detection results are lower than the total error allowable in 95% of the studied samples. To conclude with, the three coagulometers evaluated have maintenance performed and are calibrated according to the international guidelines, and the results obtained with an optical or mechanical clot detection method are equivalent.

O objetivo deste estudo foi determinar se a detecção foto-óptica do coágulo é equivalente à detecção eletromecânica ao realizar o tempo de protrombina (TP), o tempo de tromboplastina parcial ativado (APTT) e a dosagem de fibrinogênio (FBG). Foram estudados 258 pacientes consecutivos que concorreram ao laboratório para realizar estudos de hemostasia. Foram utilizados três coagulómetros: ACL TOP (foto-óptico) e STArt e Destiny plus como detecção eletromecânica. O TP, APTT e FBG foram realizados em todos os equipamentos antes de decorridas três horas da tomada da amostra. Uma boa correlação foi conseguida entre os resultados obtidos com ambos os métodos de detecção TP (%): (ACL TOP vs. STArt R=0,989; ACL TOP vs. Destiny plus R =0,988), APTT: (ACL TOP vs.STArt R=0,938; ACL TOP vs. Destiny Plus R=0,989), e FBG (ACL TOP vs. STArt R=0,97; ACL TOP vs. Destiny Plus R=0,984). A diferença dos resultados entre plataformas é menor ao erro total permitido estabelecido pelos critérios de CLIA (ETa TP e APTT =15% e FBG 20%) em 95% das amostras. Nos três coagulómetros avaliados, corretamente mantidos e calibrados a detecção foto-óptica lança resultados equivalentes à detecção eletromecânica.

Tromboelastometría y tromboelastografía / Thromboelastography and Thromboelastometry / Tromboelastometria e tromboelastografia

La tromboelastometría (TEM) y tromboelastografía (TEG) describen la interacción entre factores de coagulación, fibrinógeno, plaquetas y sistema fibrinolítico en sangre entera, en tiempo real, y se evalúan las características cinéticas y viscoelásticas del coágulo. La TEG ha sido descripta hace varias décadas, pero con el advenimiento de equipos, tromboelastógrafos y tromboelastómetros rotacionales, a través del uso de agonistas para activar el sistema de coagulación de manera de reducir los tiempos de reacción y el análisis de los parámetros a través de programas computarizados se han transformado en herramientas útiles en el manejo del sangrado. Se ha incrementado la bibliografía en los últimos años sobre el uso de estas pruebas para el manejo transfusional en situaciones como trauma, cirugías, y hemorragias post parto. En la presente actualización se describirán las pruebas, su interpretación y su utilidad.

Thromboelastography (TEG) and thromboelastometry (TEM) describe the interaction between coagulation factors, fibrinogen, platelets and members of the fibrinolytic system in whole blood, in real time, assessing the kinetic and viscoelastic characteristics of the clot formed. TEG was described many decades ago, but the introduction of new instruments, thromboelastograph and rotational tromboelastometers, using agonists to activate the coagulation system that reduced time for results and software that allowed for the analysis of parameters, transformed these tests into useful tools in the management of the bleeding. In recent years, the literature has increased over the use of these tests for transfusion management in situations such as trauma, surgery, and post-partum bleeding. The present update will be describing these tests, their interpretation and usefulness.

A tromboelastometria (TEM) e tromboelastografia (TEG) descrevem a interação entre fatores de coagulação, fibrinogênio, plaquetas e sistema fibrinolítico em sangue inteiro, em tempo real, avaliando as características cinéticas e viscoelásticas do coágulo. A TEG foi descrita faz várias décadas, mas com a chegada de equipamentos, tromboelastógrafos e tromboelastômetros rotacionais, através do uso de agonistas para ativar o sistema de coagulação de maneira de reduzir os tempos de reação e a análise dos parâmetros através de programas computadorizados transformaram-se em ferramentas úteis no manejo do sangramento. Nos últimos anos, houve um incremento da bibliografia sobre o uso destes testes para o manejo transfusional em situações como trauma, cirurgias, e hemorragias pós-parto. Na presente atualização serão descritos os testes, sua interpretação e sua utilidade.

Anticoagulant and factor Xa-like activities of Tityus discrepans scorpion venom

Tityus discrepans venom (TdV) produces a variety of haemostatic manifestations including alveoli fbrin deposition and/ or prothrombin and partial thromboplastin time (PT, PTT) alterations in mammals. In vitro studies have demonstrated that TdV contains tissue plasminogen activator-like (t-PA), fbrinolytic and plasmin inhibitory compounds and produces platelets activation through GPVI and a novel Src-dependent signalling pathway. The aim of this study is to describe the initial characterization of procoagulant and anticoagulant components from TdV. This venom was fractionated by exclusion molecular chromatography on a Sephadex G-50 column. The eluted material was collected as fve fractions called S1 to S5. These fractions and the whole venom were used to evaluate factor Xa- and thrombin-like activities, fbrinogen degradation, furthermore thrombin- and factor Xa-inhibitory activities. The results demonstrated that TdV contain components with factor Xa-like activity (procoagulants) as well fbrinogenolytic compounds present in the fraction S1 and components with factor Xa inhibitory activity in the fractions S4 and S5 (anticoagulants).

El veneno de Tityus discrepans (TdV) produce en mamíferos una variedad de manifestaciones hemostáticas tales como depósitos de fbrina en alveolos y/o alteración en los tiempos de protrombina y tromboplastina parcial (PT, PTT). Estudios in vitro han demostrado que el TdV contiene componentes semejantes al activador del plasminógeno tipo tisular (t-PA), fbrino-líticos, compuestos que inhiben la actividad de plasmina y además componentes que promueven la activación de plaquetas a través del receptor GPVI y por una nueva vía de señalización dependiente de las Src kinasas. El objetivo de este estudio es describir la caracterización inicial de componentes procoagulantes y anticoagulantes a partir del TdV. Este veneno fue fraccionado por cromatografía de exclusión molecular sobre una columna Sephadex G-50. El material eluido fue colectado en cinco fracciones denominadas S1 a S5. Estas fracciones y el veneno completo fueron usados para evaluar actividades semejantes a factor Xa y trombina, degradación de fbrinógeno, como también la inhibición de la actividad del factor Xa y de la trombina. Los resultados demostraron que TdV contiene componentes con actividad semejante al factor Xa (procoagulantes) y compuestos fbrinogenolíticos presentes en la fracción S1, además de componentes con actividad inhibitoria del factor Xa presentes en la fracción S4 y S5 (anticoagulantes).

In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 μg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can.

Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina / Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR); cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K), preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral) o placebo. El punto final primario, INR < 3.5 a las 24 horas de administrar la dosis, se alcanzó en 70% de los pacientes en Vit-K y 20% en placebo. La reducción absoluta del riesgo y su intervalo de confianza de 95%: RAR (IC95%) = 50% (14.4 a 85.6) ρ = 0.028; NNT (IC95%) = 2(1.3 a 6.9); no se registraron eventos adversos, ni INR < 2 luego de 24 horas de tratamiento. Los resultados obtenidos son consistentes con estudios donde se administró Vit-K en preparación específica para vía oral. Así la Vit-K en presentación parenteral, administrada por vía oral, es más efectiva y segura que simplemente detener la administración de warfarina para revertir la excesiva anticoagulación, en donde no exista presentación específica oral de Vit-K o ésta sea muy costosa.

Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR); when safety range is exceeded, Vitamin K (Vit-K) could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation) or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point) was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR), of 50% (CI95%: 14.4-85.6) ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9). No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

Evaluating the efficiency of Plantago ovata and starch in water turbidity removal

In. the current study, the efficiency of starch and Plantago ovata extract as coagulant aids is compared in water turbidity removal. The coagulant is ferric chloride and the experiments are run in two ranges of pH 7 and 8. The achieved results of turbidity removal in different turbidity levels of 100, 50 and 20 NTU caused by different concentrations of starch and P.ovata as coagulant aids besides ferric chloride as the main coagulant are compared. According to the achieved results, the use of P.ovata or starch as the coagulant aid may play a key role in reducing the amount of FeCl[3] as the main coagulant and consequently decreasing the generated sludge. Furthermore, the remarkable turbidity removal efficiency gained when these coagulant aids are used in comparison with the case when no coagulant aid is introduced is also of interest. Generally, the both coagulant aids seem to be more efficient in pH value of 7 rather than 8. Although both coagulant aids used in this study manifested acceptable turbidity removal efficiencies, P.ovata showed higher capabilities of removal in different turbidity levels and pH values in comparison with starch

Combined coagulation flocculation pre treatment unit for municipal wastewater

The potentials of using the hydraulic technique in combined unit for municipal wastewater treatment were studied. A combined unit in which processes of coagulation, flocculation and sedimentation, has been designed utilizing hydraulic mixing instead of mechanical mixing. Ajar test treatability study has been conducted to locate the optimum dose of the coagulants to be used. Alum, ferrous sulfate, ferric sulfate, a mixture of ferric and ferrous sulfates, and mixture of lime and ferrous sulfate were all tested. A pilot unit was constructed in the existing wastewater treatment plant at El Mansoura governorate located in north Egypt. The optimum dose of coagulants used in the combined unit gives removal efficiencies for COD, BOD, and total phosphorous as 65%, 55%, and 83%, respectively

[Effectiveness of Moringa oleifera coagulant protein and chitosan as natural coagulant aids in removal of colloidal particles and bacteria from turbid waters]

In recent years, chitosan and Moringa oleifera Coagulant Protein a natural coagulant were used in order to reduce the problems occure from chemical coagulants. This investigation was done to determine effectiveness of Moringa Oleifera Coagulant Protein and Chitosan as natural coagulant aids in removal of colloidal particles and bacteria from turbid waters. In this interventional- quasi experimental study, the experiments were run by using synthetic water having low [10-20NTU], medium [100-120NTU] and high [200-220NTU] initial turbidities. In order to determine optimum pH and dosage of coagulant and coagulant aids, a conventional jar test apparatus was employed. Turbidity reading were carried out using a Hach model 2100P Turbidimeter. The samples were taken from the top four inch of the suspension for turbidity and bacteria removal measurement. Optimum dose of alum for waters with three different initial turbidities were 20, 40, and 20 mg/1, respectively. Optimum pH was between 7-7.5. Moringa oleifera Coagulant Protein and chitosan were reduced the required dosage of alum from 12.5% to 62.5% and from 50% to 87.5%, respectively, in different turbidities and residual aluminum was reduced to standard limit [0.2mg/l]. The bacteria removal efficiency were from 90% to 99.9999%. It was found when samples were stored during 24 hours; regrowth of E.coli was not observed. This study showed that natural coagulant aids can reduce the turbidity to below 5NTU without filtration in optimum condition

[Removal of excess fluoride from water plants by poly aluminum chloride as a new coagulant]

The fluoride ions are commonly found in water resources. These ions should be in optimum levels for prevention of dental caries. However, the excess value can cause such health problems as fluorosis. The aim of the present study was to investigate the removal of excess fluoride ions by using poly aluminum chloride as a new coagulant that is used in water treatment plants. All experiments were conducted in batch system. Several combinations of parameters such as initial fluoride concentration [1.4, 2 and 2.4 mg/L], pH of solution [3, 7, 9], poly aluminum concentration [10, 20, 30, 40 mg/L], and exposure time [30, 60, 90 minute] were investigated. Various concentrations of poly aluminum chloride solution at different pH levels were added into 200 ml of fluoride solution, and samples were taken in predetermined time intervals and the final concentration of fluoride was determined by spectrophotometer at 570 nm. The results showed that, the highest removal was obtained at pH=7. In addition, it was observed that fluoride removal efficiency was higher in pH=5 than in pH=9. Also the results showed that, removal efficacy can be increased by increasing the poly aluminum chloride and the exposure-time. This study denoted that removal of high levels of fluoride ions can effectively be done by using poly aluminum chloride as a new coagulant. Its use is possible in water treatment facilities without any need for modification in water treatment plans

Effectiveness of chitosan as natural coagulant aid in treating turbid waters

During the last decade, there has been a concern about the relation between aluminum residuals in treated water and Alzheimer disease, and more interest has been considered on the development of natural coagulants such as chitosan. Chitosan, a natural linear biopolyaminosaccharide, is obtained by alkaline deacetylation of chitin. The present study was aimed to investigate the effects of alum as coagulant in conjunction with chitosan as coagulant aid on the removal of turbidity, hardness and Escherichia coli from water. A conventional jar test apparatus was employed for the tests. The optimum pH was observed between 7 to 7.5 for all turbidities. The optimum doses of alum and chitosan when used in conjunction, were 10mg/L and 1mg/L, 5mg/L and 0.5mg/L, and 5mg/L and 0.5mg/L in low, medium and high turbidities, respectively. Turbidity removal efficiency was resulted between%74.3 to%98.2 by alum in conjunction with chitosan. Residual Al[+3] in treated water was less than 0.2 mg/L, meeting the international guidelines. The results showed that turbidity decrease provided also a primary Escherichia coli reduction of 2-4 log units within the first 1 to 2 hr of treatment. Hardness removal efficiency decreased when the total hardness increased from 102 to 476mg/L as CaCO3. At low initial turbidity, chitosan showed marginally better performance on hardness, especially at the ranges of 100 to 210 mg/L as CaCO3. In conclusion, coagulant aid showed a useful method for coagulation process. By using natural coagulants, considerable savings in chemicals and sludge handling cost may be achieved

Diterpenoid alkaloids from roots of Aconitum recemulosum and their inhibitory effects on PAF-induced platelet aggregation / 中国中药杂志

<p><b>OBJECTIVE</b>To study diterpenoid alkaloids from the roots of Aconitum recemulosum, and their inhibitory effects on PAF-induced platelet aggregation.</p><p><b>METHOD</b>The root of A. recemulosum was extracted with 95% EtOH. The total alkaloids extracted were isolated and purified by several kinds of column chromatography over silica gel, RP-18, and Sephadex LH-20, and identified based on spectral analysis. And the inhibitory effects of isolated compounds on PAF-induced platelet aggregation were detected.</p><p><b>RESULT</b>Five alkaloids were isolated and identified as sachaconitine (1), 14-acetylsachaconitine (2), hemsleyanine C (3), circinasine A (4), and talatisamine (5). The results showed compounds 1 and 2 have moderate inhibition effect on PAF.</p><p><b>CONCLUSION</b>Compounds 1-5 were firstly isolated from this plant. Furthermore, compounds 1 and 2 possessed moderate inhibitory effects on PAF-induced platelet aggregation.</p>

In vitro anticoagulation monitoring of low-molecular-weight heparin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.</p><p><b>METHODS</b>A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied.</p><p><b>RESULTS</b>The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.</p><p><b>CONCLUSIONS</b>The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-IIa activities.</p>

Diagnosis and treatment of congenital hemophilia with inhibitors: A Latin American perspective / Diagnóstico y tratamiento de la hemofilia congénita con inhibidores: Una perspectiva latinomericana

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.

El Comité Latinoamericano sobre la Terapéutica de Personas con Inhibidores (CLOTTING) está compuesto por un grupo de especialistas en hemofilia de Latinoamérica. El objetivo del grupo es promover la adopción de un estándar de tratamiento óptimo para los pacientes con hemofilia en Latinoamérica. La prevalencia de inhibidores en pacientes con hemofilia en Latinoamérica determina desafíos clínicos y se estima que de 1000 a 3000 pacientes en esta región están afectados con hemofilia e inhibidores. Existe una necesidad urgente de establecer un consenso regional y guías clínicas para el diagnóstico y tratamiento de estos pacientes. Nosotros presentamos una revisión exhaustiva basada en las mejores prácticas clínicas vigentes y en los datos publicados en la literatura, con una perspectiva latinoamericana, tomando en cuenta la variabilidad existente de los tratamientos de la hemofilia disponibles en los diferentes países de esta Región.

Isolation and characterization of a serine proteinase with thrombin-like activity from the venom of the snake Bothrops asper

A serine proteinase with thrombin-like activity was isolated from the venom of the Central American pit viper Bothrops asper. Isolation was performed by a combination of affinity chromatography on aminobenzamidine-Sepharose and ion-exchange chromatography on DEAE-Sepharose. The enzyme accounts for approximately 0.13 percent of the venom dry weight and has a molecular mass of 32 kDa as determined by SDS-PAGE, and of 27 kDa as determined by MALDI-TOF mass spectrometry. Its partial amino acid sequence shows high identity with snake venom serine proteinases and a complete identity with a cDNA clone previously sequenced from this species. The N-terminal sequence of the enzyme is VIGGDECNINEHRSLVVLFXSSGFL CAGTLVQDEWVLTAANCDSKNFQ. The enzyme induces clotting of plasma (minimum coagulant dose = 4.1 µg) and fibrinogen (minimum coagulant dose = 4.2 µg) in vitro, and promotes defibrin(ogen)ation in vivo (minimum defibrin(ogen)ating dose = 1.0 µg). In addition, when injected intravenously in mice at doses of 5 and 10 µg, it induces a series of behavioral changes, i.e., loss of the righting reflex, opisthotonus, and intermittent rotations over the long axis of the body, which closely resemble the `gyroxin-like' effect induced by other thrombin-like enzymes from snake venoms.

Mezclas con potencial coagulante para tratamiento de lixiviados de un relleno sanitario / Mixtures with clotting potential for the treatment of leachates of a sanitary landfill

En el manejo de residuos sólidos una alternativa es el relleno sanitario, la cual es un problema debido a que el lixiviado generado representa un riesgo de contaminación de agua y suelo. Se determinó el potencial de coagulación-floculación de mezclas con proporciones variables de almidón de plátano, sulfato de aluminio y arcillas (LASA 55; LASA 73; LASAB 23530 y LASAR 23530). Para evaluar la efectividad se corrieron testigos de coagulación con sulfato de aluminio y cloruro férrico. El lixiviado fue pretratado y se desarrollaron pruebas de jarras, midiendo turbiedad, color, demanda química de oxígeno (DQO), pH, sólidos suspendidos totales (SST) y conductividad. La turbiedad se redujo a <5UNT con 75mg·l-1 en dos tratamientos (LASA 55 y sulfato de aluminio). La mayor remoción de color se obtuvo con cloruro férrico, seguidas por LASA 55 y sulfato de aluminio, LASAB 23530 y LASA 73, siendo LASAR 23530 la menor. Las mezclas basadas en almidón más sulfato de aluminio tuvieron un bajo nivel de remoción de DQO; a diferencia de LASAR, los coagulantes convencionales presentaron mejor remoción. En cuanto a los SST y conductividad, se obtuvo una correlación muy similar entre ambas. Los resultados permitieron establecer la factibilidad de aplicar mezclas con propiedades coagulantes para el tratamiento de lixiviados o para pruebas futuras en el tratamiento de aguas residuales industriales o municipales.