Neutralization of toxic activities of Bothrops asper snake venom by ethnomedicinal plants used in Central America, with emphasis in Guatemala: a review / Neutralización de actividades tóxicas del veneno de la serpiente Bothrops asper por plantas etnomedicinales utilizadas en Centroamérica, con énfasis en Guatemala: Revisión

There are few scientific studies that explore the use of medicinal plants for snakebite envenoming in Central America, although plant-based therapies have been traditionally used in the region. This work reviews the studies conducted in Central America to assess the ability of extracts obtained from plants of local ethnomedical use to inhibit toxic activities of the venom of Bothrops asper, the snake responsible for approximately half of the snakebite envenomings in these countries. The search prioritized the description of the plants used in Guatemala, since most of the studies described in this work were conducted in that country, although references to other countries are included. Information concerning secondary metabolites and other pharmacological activities of these plant species, relevant to the treatment of snakebites, was also described. The literature search was conducted in the Google Scholar, PubMed and Scopus databases and completed with locally available literature. It was found that extracts of 12 plant species inhibited the hemorrhagic effect of the venom and three neutralized the edema-forming activity, while inhibition of proteolytic and phospholipase A2 (PLA2) activities was achieved by three and one plant species, respectively. Only Brownea rosa-de-monte was able to effectively counteract the in vitro coagulant effect of the venom. Some plant extracts screened in Guatemala demonstrated procoagulant or anti-thrombin intrinsic effects that might aggravate the coagulopathy induced by the venom. These findings underscore the need of carrying out scientific studies aimed to validate the inhibitory potential of Central American plant extracts and their metabolites against B. asper venom.

Pocos estudios científicos han explorado el uso de plantas medicinales para el tratamiento del envenenamiento ofídico en Centroamérica, a pesar de que las terapias basadas en plantas son de uso tradicional en la región. Este trabajo recopiló información sobre los estudios realizados en Centroamérica para evaluar la capacidad de extractos de plantas de uso etno-médico para inhibir las actividades tóxicas del veneno de Bothrops asper, la serpiente responsable de aproximadamente la mitad de los envenenamientos ofídicos en Centroamérica. La búsqueda priorizó la descripción de plantas utilizadas en Gua-temala, ya que la mayoría de los estudios aquí descritos fueron realizados en ese país. También se incluyó la descripción de los metabolitos secundarios y otras actividades farmacológicas de las especies evaluadas, que podrían explicar su uso como antiofídicos. La búsqueda de literatura se realizó en las bases de datos de Google Scholar, PubMed, Scopus, y se completó con literatura disponible localmente. Se determinó que 12 extractos de plantas inhibieron el efecto hemorrágico del veneno y tres el efecto edematígeno; la actividad proteolítica fue inhibida por extractos de tres especies y la fosfolipasa A2 (PLA2) por una especie. Solamente Brownea rosa-de-monte demostró inhibir efectivamente el efecto coagulante del veneno in vitro. Algunos extractos de las plantas tamizadas en Guatemala demostraron efectos procoagulantes o anti-trombina intrínsecos, que podrían agravar las alteraciones inducidas por el veneno en la coagulación. Estos hallazgos enfatizan la necesidad de validar el potencial de extractos de plantas centroamericanas y sus metabolitos secundarios para neutralizar el veneno de B. asper.

Inhibición de las actividades proteolítica y fosfolipasa A2 del veneno de Bothrops asper por el extracto etanólico de Neurolaena lobata (L) Cass / Inhibition of proteolytic and phospholipase A2 activities of Bothrops asper venom by the ethanolic extract of Neurolaena lobata (L) Cass

Neurolaena lobata es utilizada tradicionalmente en Centroamérica para tratar la mordedura de serpiente, pero su efectividad para contrarrestar el envenenamiento producido por Bothrops asper ha sido poco estudiada. Se evaluó la capacidad del extracto etanólico de sus hojas para inhibir las actividades proteolítica, fosfolipasa A2 (PLA2; evaluada como hemólisis indirecta) y coagulante del veneno in vitro. El material vegetal fue colectado en Izabal, Guatemala, secado, se hicieron extracciones con etanol y se evaluó la presencia de actividades proteolítica, PLA2 y coagulante in-trínsecas en ensayos de concentración-actividad. Los efectos inhibitorios de la actividad proteolítica y PLA2 del veneno se evaluaron después de pre-incubar concentraciones variables del extracto con concentraciones fijas de veneno. La inhibición de la actividad coagulante del veneno no fue evaluada porque el extracto presentó actividad anticoagulante intrínseca dependiente de la concentración. El extracto inhibió completamente las actividades proteolítica (CE50 = 15.7 µg/µl) y PLA2 (CE50 = 32.5 µg/µl) del veneno. El análisis fitoquímico utilizando ensayos macro y semimicrométricos de cromatografía en capa fina, demostró la presencia de flavonoides, cumarinas, saponinas, taninos, sesquiterpenlactonas y aceites esenciales en el extracto. Su efecto sobre las proteínas del veneno se evaluó por electroforesis SDS-PAGE, mostrando cambios en el patrón electroforético atribuidos a la formación de complejos moleculares con los metabo-litos del extracto. Los resultados indican que el extracto podría inhibir los efectos tóxicos del veneno inducidos por las metaloproteinasas dependientes de zinc (SVMPs) y PLA2s, pero podría afectar las alteraciones en la coagulación, coadyuvando en la desfibrinogenación inducida por el veneno.

Neurolaena lobata has been used by traditional healers in Central America to treat snakebite, but its ability to neutralize Bothrops asper envenomations needs to be proved. This study evaluated the inhibitory potential of the ethanolic extract of the leaves of N. lobata against proteolytic, phospholipase A2 (PLA2) and coagulant activities of the venom in vitro. Leaves were collected in Izabal, Guatemala, dried, extracted with ethanol and concentration-response assays were conducted to detect intrinsic proteolytic, PLA2 (evaluated as indirect hemolysis) and coagulant activities. Assays for anti-proteolytic and anti-PLA2 activities were performed after pre-incubation of several amounts of extract with a fixed concentration of venom. Inhibition assay for the coagulant effect of the venom was not tested because pre-incubation of thrombin with the extract prolonged the clotting time of plasma in a concentration-dependent manner. Proteolytic (EC50 = 15.7 µg/µl) and PLA2 (EC50 = 32.5 µg/µl) activities of the venom resulted completely inhibited by the extract. Phytochemical profiles, determined by micrometric assays and semi microanalysis by thin layer chro-matography, showed the presence of flavonoids, coumarins, saponins, tannins, sesquiterpene lactones and essential oils in the extract. SDS-PAGE was used to assess the action of the extract on the venom proteins. Results showed changes in the electrophoretic profile, probably due to the formation of insoluble complexes with plant specialized metabolites. These findings demonstrated that the extract could be able to inhibit toxic effects triggered by zinc-dependent snake venom metalloproteinases (SVMPs) y PLA2s but might aggravate the alterations induced by the venom in coagulation.

Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats / Efeitos do rocurônio, sugamadex e complexo rocurônio-sugamadex sobre a coagulação em ratos

Abstract Background and objectives: Sugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats. Methods: This is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group - 0.5 mL of intravenous saline; the Sugammadex Group - intravenous sugammadex (100 mg kg−1); and the Rocuronium-Sugammadex Group - intravenous solution with rocuronium (3.75 mg kg−1) and sugammadex (100 mg kg−1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups. Results: Platelet counts, prothrombin times, and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group (p = 0.035). Conclusions: The rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.

Resumo Introdução e objetivos: O sugamadex é uma substância farmacológica alternativa capaz de reverter o bloqueio neuromuscular sem as limitações apresentadas pelos anticolinesterásicos. Entretanto, há relatos de transtornos de coagulação relacionados ao tratamento com sugamadex sem que mecanismos exatos de seus efeitos sobre a coagulação sejam totalmente compreendidos. O objetivo da presente pesquisa foi avaliar os efeitos do rocurônio, sugamadex e do complexo rocurônio-sugamadex sobre a coagulação em um modelo experimental com ratos. Métodos: Este é um estudo randomizado experimental animal. Ratos Wistar foram aleatoriamente designados aos seguintes grupos: grupo controle; Grupo Ssal - 0,5 mL de solução salina intravenosa; Grupo sugamadex - sugamadex intravenoso (100 mg.kg-1); e Grupo rocurônio-sugamadex - solução intravenosa com rocurônio (3,75 mg.kg-1) e sugamadex (100 mg.kg-1). A anestesia foi realizada utilizando-se isoflurano com ventilação controlada. Os fatores de coagulação foram medidos 10 minutos após o final do preparo pré-operatório e 30 minutos após a administração de drogas de acordo com os grupos escolhidos. Resultados: Contagem de plaquetas, tempo de protrombina e tempo de tromboplastina parcial ativada foram semelhantes entre os grupos e entre os momentos dentro de cada grupo. Houve redução nos níveis de fibrinogênio plasmático entre os tempos 1 e 2 no grupo rocurônio-sugamadex (p = 0,035). Conclusões: O complexo rocurônio-sugamadex promoveu reduções na contagem de fibrinogênio plasmático, apesar de os níveis continuarem dentro dos limites normais.

Anticoagulación en COVID-19 / Anticoagulation in COVID-19

La vida del mundo cambió como la conocíamos, desde diciembre de 2019, por una nueva pandemia viral, el "Coronavirus 2". Virus de alta contagiosidad y gravedad por el Síndrome Respiratorio Agudo Severo (SARS CoV-2) provocando alta morbimortalidad, desbordado las Unidades de Cuidados Intensivos del mundo, para atender a estos pacientes cuyo cuadro es primariamente respiratorio. Actualmente, además se enfrenta a una segunda amenaza, el aumento sustancial en comparación a otros pacientes hospitalizados (no COVID-19) de las complicaciones tromboembólicas.Esta publicación pretende realizar una revisión de la información actualizada disponible respecto a la epidemiología, fisiopatología y manejo de la enfermedad tromboembólica en pacientes con COVID-19 hospitalizados.

The life of the world changed as we knew it, since december 2019, due to a new viral pandemic, the "Coronavirus 2". Virus of high contagiousness and severity due to Severe Acute Respiratory Syndrome (SARS CoV-2) causing high morbidity and mortality, overwhelmed the Intensive Care Units of the world, to care for these patients whose primarily respiratory symptoms. Currently, it also faces a second threat, the substantial increase compared to other hospitalized patients (not COVID-19) of thromboembolic complications.This publication aims to review the updated information available regarding the epidemiology, pathophysiology, and management of thromboembolic disease in hospitalized COVID-19 patients.

Rotational thromboelastometry assessment of ballanced crystalloid, hydroxyethyl starch and gelatin effects on coagulation: a randomized trial / Tromboelastometria rotacional na avaliação dos efeitos de cristaloides balanceados, hidroxietilamido e gelatina na coagulação: estudo randômico

Abstract Background and objectives Modern crystalloid and colloid solutions are balanced solutions which are increasingly used in perioperative period. However, studies investigating their negative effect on whole blood coagulation are missing, and vivid debate is going on about which solution has the minimal coagulopathy effect. The aim of our study was to assess the effect of modern fluid solutions on whole blood coagulation using rotational thromboelastometry. Methods Blood samples were obtained from 30 patients during knee arthroscopy before and after administration of 500 mL of crystalloid, Hydroxyethyl Starch and gelatin according to the randomization. Rotational thromboelastometry (Extem, Intem and Fibtem tests) was used to assess negative effect of fluid solutions on whole blood coagulation. Results In Extem test, the initiation phase of fibrin clot formation represented by CT parameter was not influenced by any fluid solution (p > 0.05). The speed of clot formation represented by CFT and α angle was impaired by Hydroxyethyl Starch and gelatin but not by crystalloids (p < 0.05). The strength of formatted coagulum represented by MCF parameter was impaired both in Extem and Fibtem test by HES and in Fibtem also by crystalloids (p < 0.05). Intem test was not negatively influenced by any crystalloid or colloid solution in any parameter (p > 0.05). Conclusion Extem test appears to be sensitive to coagulopathy effect of modern colloids and crystalloids. Hydroxyethyl starch has the most obvious negative effect on clot formation followed by gelatin and finally by crystalloids. Intem test seems to be insensitive to adverse effect of modern colloids and crystalloids.

Resumo Justificativa e objetivos Os cristaloides e coloides modernos são soluções balanceadas e cada vez mais utilizadas no período perioperatório. No entanto, não há estudos que avaliem seu efeito negativo na coagulação do sangue total e o intenso debate sobre a solução que cause um efeito mínimo na coagulopatia permanece. O objetivo de nosso estudo foi avaliar o efeito das soluções líquidas modernas na coagulação do sangue total com o uso da tromboelastometria rotacional. Métodos De acordo com a randomização, amostras de sangue foram colhidas de 30 pacientes durante a artroscopia de joelho, antes e após a administração de 500 mL de cristaloides, hidroxietilamido e gelatina. A tromboelastometria rotacional (testes Extem, Intem e Fibtem) foi utilizada para avaliar o efeito negativo das soluções líquidas na coagulação do sangue total. Resultados No teste Extem, a fase de iniciação da formação de coágulos de fibrina representada pelo parâmetro CT não foi influenciada por qualquer solução líquida (p > 0,05). A velocidade da formação de coágulos representada pelo CFT e pelo ângulo α foi prejudicada pelo hidroxietilamido e pela gelatina, mas não pelos cristaloides (p < 0,05). A força do coágulo formatado representado pelo parâmetro MCF foi prejudicada tanto no teste Extem quanto no teste Fibtem pelo HES e no teste Fibtem também pelos cristaloides (p < 0,05). O teste Intem não foi influenciado negativamente por nenhuma solução cristaloide ou coloide em nenhum parâmetro (p > 0,05). Conclusão O teste Extem parece ser sensível ao efeito de coagulopatia dos coloides e cristaloides modernos. O hidroxietilamido apresentou o efeito negativo mais óbvio na formação do coágulo, seguido pela gelatina e finalmente pelos cristaloides. O teste Intem parece ser insensível ao efeito adverso dos coloides e cristaloides modernos.

Aspirina ¿No más para prevención primaria? / No more aspirine for primary prevention

El uso de dosis baja de aspirina en prevención primaria de eventos cardiovasculares (CV) en sujetos sanos o aparentemente sanos es un tópico ampliamente debatido. Muchos argumentos indican que la "prevención primaria" es solo una definición convencional y que la transición a la prevención secundaria representa un continuo de elevación de valores del riesgo CV. Aunque no hay pruebas consistentes de la eficacia de la aspirina en diferentes niveles de riesgo CV, en las poblaciones de riesgo bajo parece ser menos eficiente. Esta revisión de los tres nuevos estudios aleatorios señalan que tanto los adultos aparentemente sanos y los pacientes con diabetes obtienen muy poco beneficio protector de la aspirina considerando el incremento en el riesgo de eventos de sangrado severo.(AU)

The use of low-dose aspirin in primary prevention of cardiovascular (CV) events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that "primary prevention" is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no consistent proofs of efficacy of aspirin at different CV risk levels, in low-risk population aspirin appear to be less efficient. This review of three new randomized trials indicated that both the apparently healthy adults and patients with diabetes would derive little protective benefit from aspirin considering the increased risk of severe bleeding events(AU)

Nível de informação e adesão à terapia de anticoagulação oral com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde / Knowledge and information levels and adherence to oral anticoagulant therapy with warfarin in patients attending primary health care services

A anticoagulação oral com varfarina é usada por milhões de pacientes em todo o mundo, apresentando segurança e eficácia bem estabelecidas. Ainda assim, na atenção primária à saúde, os anticoagulantes estão entre as classes de medicamentos mais associadas a erros de medicação fatais. Objetivo: Verificar o nível de informação e a adesão ao tratamento com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde. Método: Foi realizado um estudo transversal de uma coorte prospectiva com 60 pacientes em uso de varfarina no município de Ijuí, Rio Grande do Sul. Utilizou-se questionário para verificar o nível de informações dos usuários quanto à prescrição e o nível das informações prestadas pela equipe de saúde aos usuários. A Escala de Adesão Terapêutica de Morisky de Oito Itens (MMAS-8) e o coeficiente internacional normatizado ( international normalized ratio , INR) foram usados para verificar a adesão ao tratamento. Resultados: Os resultados foram expressos em valores absolutos e relativos e razão de prevalência, com seu respectivo intervalo de confiança de 95%. Verificou-se que 83,3% dos participantes tiveram nível de informação insuficiente prestada pela equipe de saúde, 50,0% não souberam informar sobre o uso correto do medicamento, 86,7% foram não aderentes ao tratamento segundo a MMAS-8, e 63,3% estavam fora do intervalo terapêutico adequado. Conclusão: Neste estudo, observou-se a necessidade de melhorar a qualidade das informações prestadas aos usuários e criar estratégias para adesão ao tratamento, visando à segurança do paciente em tratamento com varfarina na atenção primária à saúde.

Oral anticoagulation therapy with warfarin is widely used around the world and its safety and efficacy are well-established. Nevertheless, anticoagulants are among the drug classes most associated with fatal medication errors in primary health care. Objective: To investigate patient knowledge, the level of information provided, and medication adherence in patients treated with warfarin at a primary health care service. Method: A cross-sectional study of a prospective cohort of 60 patients on warfarin treatment in the town of Ijuí, Rio Grande do Sul, Brazil. A questionnaire was administered to test patients' knowledge about their prescriptions and the level of information provided by the health team. The 8-item Morisky Medication Adherence Scale (MMAS-8) and International Normalized Ratio (INR) were used to verify adherence to treatment. Results: The results were expressed in absolute and relative values and prevalence ratios were calculated, with respective 95% confidence intervals. It was found that 83.3% of the participants had been given insufficient information by the health team, 50% did not know how to use the medication correctly, 86.7% were not adherent to the treatment according to MMAS-8 and 63.3% were outside of the correct INR range. Conclusion: In this study, we observed a need to improve the quality of information provided to users and to develop strategies to improve adherence to treatment, to ensure the safety of patients treated with warfarin in primary health care services.

Eficacia de la vitamina K en los trastornos de coagulación en los pacientes con enfermedad hepática crónica / Efficacy of vitamin K in coagulation disorders in patients with chronic liver disease

La coagulopatía es el denominador común en la amplia gama de procesos hepático crónicos, efecto principal de la deficiencia de vitamina K. A pesar de la falta de evidencia que sostiene su eficacia, su administración representa una parte del manejo de muchos pacientes con coagulopatía. Por tanto, el objetivo primario de este estudio fue comparar los tiempos de coagulación tras la administración de vitamina K en pacientes con enfermedad hepática crónica y trastornos de coagulación. Se postularon como secundarios la caracterización del paciente hepatópata según grupo nosológico por edad y sexo, así como las diferencias existentes entre las pruebas de coagulación basales con respecto a cada grupo. 72 pacientes fueron reclutados en 4 grupos, grupo 1: hepatitis B inactiva (n=6), grupo 2: hepatitis B crónica-hepatitis C (n=14), grupo 3: cirrosis (n=35) y grupo 4: hepatocarcinoma (n=17), se administraron 3 dosis de vitamina K de 10 mg cada una a intervalos de 24 horas, se midieron tiempo de protrombina (TP), radio normalizado internacional (INR) y tiempo de tromboplastina parcial activado (TPT) basales y cada 24 horas después de cada dosis. Se logró establecer una diferencia estadísticamente significativa en la corrección del tiempo de protrombina (31.04±9.62 a 21.69±8.48 P˂0.0001) así como del INR (2.81±1.013 a 1.92±0.81, P˂0.0001), hubo diferencia en cuanto a grupo diagnóstico y edad de presentación, así como en cuanto a tiempos de coagulación basales según diagnóstico. Por tanto, se demostró la efectividad de la vitamina K en la corrección del TP e INR.(AU)

Coagulopathy is the common denominator in the wide range of chronic liver processes, the main effect of vitamin K deficiency. Despite the lack of evidence supporting its efficacy, its administration represents a part of the management of many patients with coagulopathy. Therefore, the primary objective of this study was to compare clotting times after vitamin K administration in patients with chronic liver disease and coagulation disorders. The characterization of the liver disease patient according to nosological group by age and sex, as well as the differences between the baseline coagulation tests with respect to each group, were postulated as secondary. 72 patients were recruited into 4 groups, group 1: inactive hepatitis B (n = 6), group 2: chronic hepatitis B-hepatitis C (n = 14), group 3: cirrhosis (n = 35) and group 4: hepatocarcinoma ( n = 17), 3 doses of vitamin K of 10 mg each were administered at 24-hour intervals, prothrombin time (TP), international normalized radius (INR) and baseline activated partial thromboplastin time (TPT) were measured and each 24 hours after each dose. It was possible to establish a statistically significant difference in the correction of prothrombin time (31.04 ± 9.62 to 21.69 ± 8.48 P˂0.0001) as well as the INR (2.81 ± 1.013 to 1.92 ± 0.81, P˂0.0001), there was a difference in terms of group Diagnosis and age of presentation, as well as baseline clotting times according to diagnosis. Therefore, the effectiveness of vitamin K in the correction of TP and INR was demonstrated

Safety and efficacy of regional citrate anticoagulation in continuous blood purification treatment of patients with multiple organ dysfunction syndrome

The aim of this study was to discuss the safety and efficacy of regional citrate anticoagulation (RCA) on continuous blood purification (CBP) during the treatment of multiple organ dysfunction syndrome (MODS). Thirty-five patients with MODS were divided into two groups: the local citrate anticoagulation (RCA) group, and the heparin-free blood purification (hfBP) group. The MODS severity was assessed according to Marshall's MODS score criteria. Blood coagulation indicators, blood pressure, filter lifespan, filter replacement frequency, anticoagulation indicators, and main metabolic and electrolyte indicators were analyzed and compared between RCA and hfBP groups. RCA resulted in lower blood pressure than hfBP. The filter efficacy in RCA treatment was longer than in the hfBP group. The blood clearance of creatine, blood urea nitrogen and uric acid was better in the RCA group. RCA also led to higher pH than hfBP. Neither treatment resulted in severe bleeding events. In addition, MODS score was positively correlated with prothrombin time and activated partial thromboplastin time but negatively correlated with platelet concentration. RCA is a safer and more effective method in CBP treatment; however, it could also lead to low blood pressure and blood alkalosis.

Virus de inmunodeficiencia humana: ¿estado de hipercoagulabilidad? Presentación de dos casos / Is AIDS a prothrombotic entity? Report of two cases

La infección por VIH ha sido reconocida en la actualidad como una condición protrombótica, reportándose en pacientes con SIDA 10 veces mayor riesgo de desarrollo de eventos tromboembólicos de los sistemas arterial y venoso; la literatura reciente ha estimado una incidencia entre el 0.26% y 7.6 %; dicha incidencia se describe asociada a infecciones. oportunistas y/o malignidades. Una variedad de mecanismos potenciales relacionados con factores del hospedador, el virus y el TARV (tratamiento antiretroviral), están implicados en el estado de hipercoagulabilidad en pacientes con SIDA, cuya fisiopatología conduce a alteraciones en la respuesta inflamatoria y de la cascada de coagulación que no han sido bien dilucidadas; sin embargo, incluye la presencia de anticuerpos anticardiolipinas, disminución de anticoagulantes naturales, y otros factores independientes que en conjunto originan morbi-mortalidad creciente si dicha predisposición a eventos trombóticos no es reconocida por el médico. Los autores de este artículo describen 2 casos de eventos trombóticos en pacientes con síndrome de inmunodeficiencia humana hospitalizados en el Servicio de Medicina Interna de Hospital Universitario de Caracas(AU)

AIDS infection has now been recognized as a prothrombotic condition reported in patients with this disease, and have been found 10 times at greater risk of developing thromboembolic events with systemic involvement. Recent literature has estimated an incidence between 0.26% and 7.6%, also described in association with opportunistic infections and / or malignancies. A variety of potential mechanisms related to host factors, virus and antiretroviral therapy (ART) are implicated in the hypercoagulability status in HIV-positive patients, the pathophysiology leading to alterations in the inflammatory response and the coagulation cascade. It has not been well understood and includes the presence of anticardiolipin antibodies, reduction of natural anticoagulants, and other independent factors that lead to increased morbidity and mortality if such predisposition to thrombotic events is not recognized by the clinician. The authors of this article describe 2 cases of thrombotic events in patients with human immunodeficiency syndrome hospitalized in the Hospital Universitario of Caracas, Venezuela(AU)

Suspensión de la anticoagulación oral en pacientes con fibrilación auricular ante un procedimiento invasivo: ¿deben recibir un puenteo con anticoagulación parenteral durante su realización? / Suspension of oral anticoagulation in patients with atrial fibrillation before an invasive procedure: should they receive parenteral anticoagulation bridging during its implementation?

En la actualidad, muchos pacientes con fibrilación auricular son anticoagulados por largos períodos. Durante este tiempo pueden ser sometidos a procedimientos invasivos. A partir de una viñeta clínica, un médico se plantea el impacto de utilizar o no heparina de bajo peso molecular como puente farmacológico al momento de suspender la anticoagulación oral. Luego de realizar una búsqueda ad hoc, un ensayo clínico aleatorizado de no inferioridad demuestra que en pacientes con fibrilación auricular, con puntajes de riesgo tromboembólico (CHADS2) intermedios a bajos que requieren una interrupción temporal del tratamiento con warfarina para un procedimiento invasivo electivo, la estrategia de no reemplazar la anticoagulación oral con heparina de bajo peso molecular no resultó inferior (o menos efectiva) para la prevención de tromboembolismo arterial, y disminuyó además el riesgo de sangrado mayor en comparación al uso de un puente con esta medicación. (AU)

Many patients with atrial fibrillation are anticoagulated for long periods. During this time they may be subjected to invasive procedures. From a clinical vignette, a physician discusses the impact of using (or not) low molecular weight heparin as a pharmacological bridge at the time of suspending oral anticoagulation. After conducting a bibliographic search, a no inferiority randomized clinical trial showed that in patients with atrial fibrillation with intermediate to low thromboembolic risk (CHADS2) requiring a temporary interruption of warfarin therapy for an elective invasive procedure, the strategy of with holding low molecular weight heparin bridging was not inferior (or less effective) for the prevention of arterial thromboembolism than its use, also decreasing the risk of major bleeding. (AU)

Fases pré-analítica, analítica e pós-analítica no monitoramento laboratorial da anticoagulação com antagonistas da vitamina K / Pre-analytical, analytical, and post-analytical phases in laboratory monitoring of anticoagulant therapy with vitamin K antagonists

A trombose é uma doença caracterizada por eventos de hipercoagulabilidade. A terapêutica anticoagulante oral com antagonistas da vitamina K (AVKs) é amplamente indicada para prevenção e/ou controle de distúrbios da coagulação. O manuseio de administração dos AVKs é difícil devido à complexidade da definição da dose. Em geral, o monitoramento de indivíduos submetidos à terapêutica com AVK é realizado pela determinação do tempo de protrombina, em que se avalia o grau de anticoagulação através do coeficiente internacional normatizado. Invariavelmente, o fluxo do processamento laboratorial, que compreende as fases pré-analítica, analítica e pós-analítica, é importante para a fidedignidade dos resultados, repercutindo na conduta médica de forma determinante. O objetivo deste estudo foi a realização de uma revisão da literatura científica descritiva utilizando bases de dados eletrônicos para busca de materiais científicos, como Google Scholar, MEDLINE, LILACS, PubMed, SciELO e Science Direct. Abordamos alguns aspectos relacionados ao fluxo analítico da monitoração laboratorial em um laboratório de análises clínicas. Em conclusão, é necessária uma apropriada condução das fases analíticas para que seja possível o sucesso terapêutico com uso dos AVKs (AU)

Thrombosis is a disease characterized by hypercoagulable events. Oral anticoagulant therapy with vitamin K antagonists (VKAs) is widely indicated for prevention and/or control of coagulation disorders. The administration of VKAs is difficult because of the complexity of dose setting. In general, individuals submitted to VKA therapy are monitored by prothrombin time, in which the degree of anticoagulation is assessed by the international normalized ratio. Invariably, the flow of laboratory processing, which comprises pre-analytical, analytical, and post-analytical phases, is of importance to the trustworthiness of results, with significant consequences to the medical practice. The purpose of this study was to carry out a review of the scientific literature using electronic databases to search for scientific materials, such as Google Scholar, MEDLINE, LILACS, PubMed, SciELO, and Science Direct. We discuss some aspects related to the analytical flow of laboratory monitoring in a clinical laboratory. In conclusion, appropriate management of the analytical phases is necessary so that therapeutic success using VKAs is possible (AU)

Lonomia obliqua Walker (Lepidoptera: Saturniidae): hemostasis implications / Lonomia obliqua Walker (Lepidoptera: Saturniidae): implicações em hemostasia.

Summary In southern Brazil, since 1989, several cases of accidents produced by unwilling contact with the body of poisonous caterpillars of the moth species Lonomia obliqua Walker, 1855 (Lepidoptera: Saturniidae), were described. L. obliqua caterpillars have gregarious behavior and feed on leaves of host trees during the night, staying grouped in the trunk during the day, which favors the occurrence of accidents with the species. This caterpillar has the body covered with bristles that on contact with the skin of individuals, breaks and release their contents, inoculating the venom into the victim. The basic constitution of the venom is protein and its components produce physiological changes in the victim, which include disturbances in hemostasis. Hemorrhagic syndrome associated with consumption coagulopathy, intravascular hemolysis and acute renal failure are some of the possible clinical manifestations related to poisoning by L. obliqua. Specific laboratory tests for diagnosis of poisoning have not been described previously. The diagnosis of poisoning is made based on the patient's medical history, clinical manifestations, erythrocyte levels, and, primarily, parameters that evaluate blood coagulation. Treatment is performed with the use of supportive care and the administration of specific hyperimmune antivenom. Poisoning can be serious and even fatal.

Na região Sul do Brasil, a partir de 1989, foram descritos inúmeros casos de contato acidental com o corpo de lagartas venenosas da mariposa da espécie Lonomia obliqua Walker, 1855 (Lepidoptera: Saturniidae). As lagartas de L. obliqua possuem comportamento gregário e alimentam- -se de folhas das árvores hospedeiras durante a noite, permanecendo agrupadas no tronco durante o dia, o que favorece a ocorrência de acidentes. Essa lagarta possui o corpo recoberto por cerdas urticantes, que, ao contato com a pele dos indivíduos, se rompem e liberam seu conteúdo, inoculando o veneno na vítima. A constituição básica do veneno é proteica e seus componentes produzem modificações fisiológicas no acidentado, que incluem distúrbios na hemostasia. Síndrome hemorrágica associada a coagulopatia de consumo, hemólise intravascular e insuficiência renal aguda são algumas das manifestações clínicas possíveis relacionadas ao envenenamento por L. obliqua. Ainda não foram descritas avaliações laboratoriais específicas para diagnóstico do envenenamento, que é feito com base na anamnese do paciente, nas manifestações clínicas, nos índices hematimétricos e, principalmente, nos parâmetros que avaliam a coagulação sanguínea. A terapêutica é feita com a utilização de medidas de suporte e com a administração de um soro heterólogo hiperimune específico. Os envenenamentos podem ser graves e até mesmo fatais.

Dolor recurrente en fosa iliaca derecha en niños: reporte de dos casos asociados a alergia alimentaria / Recurrent right iliac fossa pain in children: two cases report related to food allergy

Objetivo: Presentar dos casos de alergia alimentaria de presentación poco común y discutir el enfoque diagnóstico de DAR en niños Casos: Caso N° 1: Niña de 11 años, aqueja dolor en fosa iliaca derecha hace 3 meses. Antecedentes: Prematuridad, atopía (dermatitis, rinitis, cólicos). Hermana y madre atópicas. Al examen físico: Dolor exquisito a la palpación de fosa iliaca derecha, cuerda cólica bilateral. Piel seca. Laboratorio: Hematobiometría sin alteraciones. Examen de orina normal, parasitológico seriado (-). EDN (neurotoxina derivada de eosinófilos) fecal >3210 ng/ml (V.N. <360 ng/ml). Colonoscopía: hiperplasia linfoidea de íleon. Caso N° 2: Niño de 9 años. Dolor en fosa iliaca derecha hace tres meses dolor abdominal localizado en fosa iliaca derecha, a predominio nocturno y con irradiación a muslo derecho. Un psiquiatra infantil le prescribe antidepresivos. Antecedentes personales: Lactancia mixta. Atopía: Asma, dermatitis atópica, cólicos de lactante. Antecedentes familiares: Madre alérgica a alimentos, padre presenta rinitis. Al examen físico: Cuerda cólica bilateral. Dolor a la palpación en fosa iliaca derecha. Laboratorio: Inmunoglobulina E 160,5 UI/ml (V.N. < 90). Colonoscopía: Hiperplasia linfoidea en íleon distal. Ambos casos mejoraron con dieta hipoalergénica. Conclusión: En presencia de hiperplasia nodular linfoide de íleon y antecedentes familiares y/o personales de atopía, debemos considerar en el diagnóstico diferencial de dolor abdominal recurrente de fosa iliaca derecha a la alergia alimentaria. La dieta de eliminación es diagnóstica y terapéutica a su vez.

Objective: To present two cases of food allergy of uncommon presentation and discuss the diagnostic approach to give in these cases: Case N° 1: 11-year-old girl, afflicting pain in the right iliac fossa 3 months ago. Background: Prematurity, atopy (dermatitis, rhinitis, cramping). Sister and mother are atopic too. The physical exam show exquisite pain on right iliac fossa at palpation. Laboratory: Urine normal, parasitological serial negative. EDN (neurotoxin derived from eosinophils) fecal >3210 ng/ml (V. N. < 360 ng/ml). Colonoscopy: lymphoid hyperplasia of ileum. Case N° 2: Child of 9 years of age. Right fossa iliac painful three months ago, predominantly nocturnal and with irradiation to right thigh. A child psychiatrist may prescribe antidepressants. Personal History: Breastfeeding and formula since newborn. Atopy: asthma, atopic dermatitis, infant colic. Family history: Mother allergic to food, father presents rhinitis. The physical examination: Pain on palpation in the right iliac fossa. Laboratory: Immunoglobulin E 160.5 IU/ml (V. N. < 90) Colonoscopy: lymphoid hyperplasia in the distal ileum. Both cases relieved by hypoallergenic diet. Conclusion: When both, ileal nodular lymphoid hyperplasia and atopy personal or familiar are present, we must be think in food allergy as differential diagnosis of recurrent abdominal pain of right iliac fosse in children. The elimination diet is diagnostic and therapeutic.

Calidad de las tromboplastinas utilizadas en el laboratorio clínico y en los equipos POCT y su impacto en la dosificación de acenocumarol en pacientes con terapia anticoagulante oral / Types of thromplastin used for INR determination in patients under chronic oral anticoagulant treatment: discrepancies that may affect the dose of coumarin derivatives needed for treatment safety

Antecedentes: El monitoreo del tratamiento con anticoagulantes cumarínicos se realiza a través del INR (International Normalized Ratio) que es el parámetro estandarizado del Tiempo de Protrombina. Las recomendaciones de la OMS indican que la precisión en el cálculo del INR puede ser mejorada usando reactivo de tromboplastina con Indice de Sensibilidad Internacional (ISI) bajo, considerándose como ISI de referencia internacional el valor 1,0. Debido a incongruencias observadas en los INR de pacientes controlados en el Servicio de Salud Metropolitano Occidente, comparando valores de muestra venosa con resultados de INR capilar obtenidos en el mismo paciente el mismo día y hora (con reactivos Tromboplastina de distinto ISI), se efectuó un ensayo clínico cruzado entre los distintos métodos. Materiales y métodos: En 100 pacientes se comparó INR venoso con dos tromboplastinas de diferente ISI (1,3 y 1,0) vs aquel efectuado con muestra capilar (ISI 1,0). Resultados: Los resultados del estudio muestran que a partir de valores de INR 3,0 las determinaciones obtenidas usando Tromboplastina de cerebro de conejo ISI=1,3 subestiman el valor de INR para un mismo paciente y una misma muestra. Conclusiones: El uso de Tromboplastina recombinante humana ISI 1,0 permite evitar la subestimación del INR en pacientes con mayor riesgo tromboembóli-co (indicación de INR objetivo más alto). Por ello, este método se adoptó en el control del TACO en pacientes controlados en el Servicio de Salud Occidente.

Background: INR (International Normalized Ratio) is the standard Prothrombin Time parameter for monitoring anticoagulant treatment with coumarin derivatives Recommendations of WHO indicate that precision in the calculation of the INR can be improved using thromboplastins with a low Index of International Sensibility (ISI=1,0). Discrepancies in INR obtained using either this technique or conventional rabbit brain derived reagents in the same sample in patients attending the Servicio de Salud Metropolitano Occidente (West Metropolitan Health Service) were observed. Our objective was to evaluate these discrepancies in a systematic way. Materials and methods: A comparative study was conducted using two thromboplastins of different ISI (1.0 and 1.3) for the calculation of venous INR in comparison with capillary INR in 100 patients. Results: The study showed that INR values may differ significantly according to the method used. In particular, rabbit brain thromboplastin ISI = 1.3 underestimates the value of INR in the range of INR ≥3.0. Conclusions: The use of human recombinant thromboplastin ISI= 1.0. for determination of INR may significantly decrease the risk of hemorrhagic complications in patients requiring higher levels of anticoagulation.

Can we more efficiently save patients with vitamin K-dependent coagulopathy caused by superwarfarin intoxication?

No abstract available.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Effect of 6% Hydroxyethyl Starch 130/0.4 as a Priming Solution on Coagulation and Inflammation Following Complex Heart Surgery

PURPOSE: Prolonged duration of cardiopulmonary bypass aggravates the degree of inflammation and coagulopathy. We investigated the influence of 6% hydroxyethyl starch (HES) 130/0.4 on coagulation and inflammation compared with albumin when used for both cardiopulmonary bypass priming and perioperative fluid therapy in patients undergoing complex valvular heart surgery. MATERIALS AND METHODS: Fifty four patients were randomly allocated into albumin-HES, albumin-nonHES, and HES-HES groups. The cardiopulmonary bypass circuit was primed with 5% albumin in the albumin-HES and albumin-nonHES group, and with HES in the HES-HES group. As perioperative fluid, only plasmalyte was used in the albumin-nonHES group whereas HES was used up to 20 mL/kg in the albumin-HES and albumin-HES group. Serial assessments of coagulation profiles using the rotational thromboelastometry and inflammatory markers (tissue necrosis factor-alpha, interleukin-6, and interleukin-8) were performed. RESULTS: Patients' characteristics and the duration of cardiopulmonary bypass (albumin-HES; 137+/-34 min, HES-HES; 136+/-47 min, albumin-nonHES; 132+/-39 min) were all similar among the groups. Postoperative coagulation profiles demonstrated sporadic increases in clot formation time and coagulation time, without any differences in the actual amount of perioperative bleeding and transfusion requirements among the groups. Also, inflammatory markers showed significant activation after cardiopulmonary bypass without any differences among the groups. CONCLUSION: Even in the presence of prolonged duration of cardiopulmonary bypass, HES seemed to yield similar influence on the ensuing coagulopathy and inflammatory response when used for priming and perioperative fluid therapy following complex valvular heart surgery compared with conventional fluid regimen including albumin and plasmalyte.

Effect of intraoperative HES 6% 130/0.4 on the need for blood transfusion after major oncologic surgery: a propensity-matched analysis

OBJECTIVES: To evaluate the effect of the intraoperative use of hydroxyethyl starch on the need for blood products in the perioperative period of oncologic surgery. The secondary end-points included the need for other blood products, the clotting profile, the intensive care unit mortality and length of stay. METHODS: Retrospective observational analysis in a tertiary oncologic ICU in Brazil including 894 patients submitted to oncologic surgery for a two-year period from September 2007. Patients were grouped according to whether hydroxyethyl starch was used during surgery (hydroxyethyl starch and No-hydroxyethyl starch groups) and compared using a propensity score analysis. A total of 385 propensity-matched patients remained in the analysis (97 in the No-hydroxyethyl starch group and 288 in the hydroxyethyl starch group). RESULTS: A higher percentage of patients in the hydroxyethyl starch group required red blood cell transfusion during surgery (26% vs. 14%; p = 0.016) and in the first 24 hours after surgery (5% vs. 0%; p = 0.015) but not in the 24- to 48-hour period after the procedure. There was no difference regarding the transfusion of other blood products, intensive care unit mortality or length of stay. CONCLUSION: Hydroxyethyl starch use in the intraoperative period of major oncologic surgery is associated with an increase in red blood cell transfusions. There are no differences in the need for other blood products, intensive care unit length of stay or mortality. .

When blood is thinner than water.

Antagonists of vitamin K dependant clotting factors are commonly used as treatment/prophylaxis for anticoagulation. Due to their narrow therapeutic window, a wide range of complications including death may occur. International normalized ratio (INR) is monitored to measure adequacy/excess of anticoagulation. There is a plethora of risk factors that may contribute to the uncontrollably high INR values. We describe our experience of a case of deep venous thrombosis wherein the patient had an overshoot of INR during anticoagulation therapy. We review the literature and discuss management in such scenarios.