Clinical relevance of genetic variants in the von Willebrand factor according to in-silico methods.

Clinical interpretation of genetic variants in the context of the patient's phenotype is a time-consuming and costly process. In-silico analysis using in-silico prediction tools, and molecular modeling have been developed to predict the influence of genetic variants on the quality and/or quantity of the resulting translated protein, and in this way, to alert clinicians of disease likelihood in the absence of previous evidence. Our objectives were to evaluate the success rate of the in-silico analysis in predicting the disease-causing variants as pathogenic and the single-nucleotide variants as neutral, and to establish the reliability of in-silico analysis for determining pathogenicity or neutrality of von Willebrand factor gene-associated genetic variants. Using in-silico analysis, we studied pathogenicity in 31 disease-causing variants, and neutrality in 61 single-nucleotide variants from patients previously diagnosed as type 2 von Willebrand disease. Disease-causing variants and non-synonymous single-nucleotide variants were explored by in-silico tools that analyze the amino acidic sequence. Intronic and synonymous single-nucleotide variants were analyzed by in-silico methods that evaluate the nucleotidic sequence. We found a consistent agreement between predictions achieved by in-silico prediction tools and molecular modeling, both for defining the pathogenicity of disease-causing variants and the neutrality of single-nucleotide variants. Based on our results, the in-silico analysis would help to define the pathogenicity or neutrality in novel genetic variants observed in patients with clinical and laboratory phenotypes suggestive of von Willebrand disease.

Type 2A and 2M von Willebrand Disease: Differences in Phenotypic Parameters According to the Affected Domain by Disease-Causing Variants and Assessment of Pathophysiological Mechanisms.

Type 2A and 2M von Willebrand disease (VWD) broadly show similar phenotypic parameters, but involve different pathophysiological mechanisms. This report presents the clinical and laboratory profiles of type 2A and type 2M patients genotypically diagnosed at one large center. Higher bleeding score values and a higher incidence of major bleeding episodes were observed in type 2A compared with type 2M, potentially reflective of the absence of large and intermediate von Willebrand factor (VWF) multimers in 2A. In type 2A, most of disease-causing variants (DCVs) appeared to be responsible for increased VWF clearance and DCV clustered in the VWF-A1 domain resulted in more severe clinical profiles. In type 2M, DCV in the VWF-A1 domain showed different laboratory patterns, related to either reduced synthesis or shortened VWF survival, and DCV in the VWF-A2 domain showed patterns related mainly to shortened survival. VWF-type 1 collagen binding/Ag (C1B/Ag) showed different patterns according to DCV location: in type 2A VWD, C1B/Ag was much lower when DCVs were located in the VWF-A2 domain. In type 2M with DCV in the VWF-A1domain, C1B/Ag was normal, but with DCV in the VWF-A2 domain, C1B/Ag was low. The higher frequency of major bleeding in VWD 2M patients with DCV in the VWF-A2 domain than that with DCV in the VWF-A1 domain could be a summative effect of abnormal C1B/Ag, on top of the reduced VWF-GPIb binding. In silico modeling suggests that DCV impairing the VWF-A2 domain somehow modulates collagen binding to the VWF-A3 domain. Concomitant normal FVIII:C/Ag and VWFpp/Ag, mainly in type 2M VWD, suggest that other nonidentified pathophysiological mechanisms, neither related to synthesis/retention nor survival of VWF, would be responsible for the presenting phenotype.

Evaluación de una clave taxonómica, para la identificación de los géneros de helechos (Monilophyta), en Guatemala / Evaluation of a taxonomic key, for the identification of fern genera (Monilophyta), in Guatemala

El desarrollo de las tecnologías de la información y la comunicación han llevado a un cambio en la manera en que se realizan las actividades de diferentes disciplinas, incluso de las más tradicionalistas, como la taxonomía botánica. Se documentó la revisión y validación colaborativa de la primera versión de una clave dicotómica para la identificación taxonómica de los géneros de helechos en Guatemala. Con este esfuerzo, se fundamentó la elaboración de una clave mejorada, su segunda versión, la cual se espera sea accesible para usuarios entrenados en morfología botánica, pero no especializados en la taxonomía específica de los helechos. La segunda versión supera las dificultades que fueron analizadas sobre la primera, y agrega contenido útil para la identificación más precisa de los géneros. Se presentan, además, los siguientes documentos suplementarios en versión electrónica: la versión más actualizada de la clave dicotómica, una lista anotada de la taxonomía supra específica de helechos en Guatemala y una lista de algunos sinónimos taxonómicos de los nombres científicos actuales, respecto a los utilizados en la Flora Mesoamericana. Esta experiencia representa un avance en la transformación de la botánica taxonómica, ya que trasciende de ser una disciplina practicada por pocos, donde prevalece sobre todo el criterio de una autoridad casi incuestionable, a una práctica colaborativa, donde el conocimiento se difunde desde la formulación y revisión de los instrumentos taxonómicos. Se espera que todos estos documentos puedan continuar siendo actualizados de manera dinámica, como un avance de la aplicación de las nuevas tecnologías a la taxonomía botánica.

The procedures of several scientific disciplines are changing with the spreading of new information and communication technologies, even the most traditional, like botanical taxonomy. Here we document the review and validation, by collaborative efforts, on the first version of the taxonomic key for the identification of the fern genera in Guatemala. An upgraded version was composed which is easier to follow and more precise. It is intended to be accessible for a wide range of interested people, more than just the fern specialists. Along with this paper, electronic supplementary documents are published too, including the most recent version of the key, an annotated list of taxonomic categories of ferns of Guatemala in the supra-specific levels, and some lists of taxonomic synonymy of the currently valid names, with reference to the old names used in Flora Mesoamericana. With this experience a new milestone has been reached by the national taxonomy, getting over the old paradigm in which taxonomy was an exclusive practice, endeavored by few authorities, to become a more inclusive discipline, embracing the development and revision of its instruments. In the future, we hope to maintain updated all these documents in a more dynamic way, applying new technologies to the taxonomic botany practices.

[Argentine Consensus in effective management of anticoagulation clinics for the use of vitamin k antagonists]. / Consenso Argentino en gestión efectiva de clínicas de anticoagulación para el uso de antagonistas de la vitamina k.

Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

Consenso argentino en gestión efectiva de clínicas de anticoagulación para uso de antagonistas de la vitamina K / Argentine consensus in effective management of anticoagulation clinics for the use of vitamin K antagonists

Resumen El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

Abstract Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

Phenotypic Parameters in Genotypically Selected Type 2B von Willebrand Disease Patients: A Large, Single-Center Experience Including a New Novel Mutation.

von Willebrand disease type 2B (VWD2B) expresses gain-of-function mutations that enhance binding of an individual's von Willebrand factor (VWF) to its platelet ligand, glycoprotein Ib (GPIb), and which are usually identified by increased ristocetin-induced platelet aggregation (RIPA). We describe here the phenotypic profile of 38 genotypically selected VWD2B-affected family members (AFMs) belonging to 19 unrelated families. Major bleeding was observed in 68.4% of AFMs (previous to their diagnosis and registered by lifetime interviews), with a total of 46 episodes (1.21/patient), and was found to be highly related to the individual bleeding score and presence of thrombocytopenia, but otherwise unrelated to other laboratory parameters. Excessive muco-cutaneous bleeding symptoms were often reported, the most frequent of which comprised menorrhagia, epistaxis, easy bruising, and bleeding after teeth extraction/in oral cavity. Eight unaffected family members were also studied. The prevalence of VWD2B within families was 0.826, and the penetrance of mutations was complete, making it mandatory to study entire family sets to complete diagnostic profiles. Seven heterozygous missense mutations were found, the most common being p.V1316M. In the p.R1308C group, 75% of the AFMs showed absence of RIPA at 0.5 mg/mL, 66.6% of whom had VWF:RCo < 10 IU/dL, and 50% of whom had VWF:CB < 10 IU/dL. In the p.S1310F group, none of the AFMs had VWF:RCo/VWF:Ag < 0.6 (RCo/Ag), but 100% had VWF:CB/VWF:Ag < 0.6/(CB/Ag). Patients with p.P1266L and p.R1304V were characterized as atypical VWD2B. Two de novo mutations were found in four AFMs belonging to two families. We also describe a novel mutation: p.Y1258C. Of our patients, 70.5% had O blood group. In conclusion, a normal RCo/Ag and a negative RIPA at 0.5 mg/mL do not necessarily rule out a diagnosis of VWD2B.

Factor von Willebrand y Enfermedad de von Willebrand: nuevos enfoques diagnósticos / Von Willebrand Factor and von Willebrand disease: new approaches to diagnosis / Fator Von Willebrand e doença de von Willebrand: novas abordagens diagnósticas

El factor von Willebrand (VWF) es una glicoproteína que se sintetiza en células endoteliales y en megacariocitos. Su vida media es de ~12 horas. Está formado por multímeros de diferentes pesos moleculares, pequeños, intermedios, grandes y extragrandes. La actividad funcional reside en los multímeros grandes, y los extragrandes son trombogénicos. Promueve la adhesión plaquetaria al subendotelio, la agregación plaquetaria y transporta al FVIII en plasma, protegiéndolo de su degradación por proteasas. La enfermedad de von Willebrand es el trastorno hemorrágico más frecuente; se describen deficiencias cuantitativas (parcial: VWD1; total: VWD3) o defectos cualitativos (VWD2A, VWD2M, VWD2B y VWD2N). La expresión clínica es variable (sangrado muco-cutáneo) y su herencia autosómica, dominante o recesiva, según las variantes. Los niveles del VWF dependen de factores genéticos y no genéticos que afectan el diagnóstico y la expresión clínica. Para llegar al diagnóstico se precisan varias pruebas, algunas inespecíficas. El laboratorio comienza con pruebas orientadoras, se continúa con pruebas confirmatorias, y posteriormente pruebas para definir la variante de VWD. El diagnóstico genotípico es fundamental para lograr el diagnóstico diferencial entre VWD2B vs. PT-VWD y VWD2N vs. Hemofilia A (leve-moderada), diferenciar VWD de AVWS y discriminar variantes VWD2.

Von Willebrand factor (VWF) is a glycoprotein with essential roles in both primary and secondary hemostasis, synthesized by endothelial cells and megakaryocytes. Its half-life is ~12 hours. VWF consists in multimers of different molecular weight: small, intermediate, large and ultra large. The functional activity resides in the large multimers; the ultra large are thrombogenic. VWF promotes platelet adhesion to subendothelium, platelet aggregation and binds FVIII, protecting it from proteolysis and preserving its hemostatic function. Von Willebrand disease is the most common bleeding disorder; qualitative defects (VWD2A, VWD2M, VWD2B and VWD2N) and quantitative deficiencies (VWD1 and VWD3) are described. The clinical expression is variable (mucocutaneous bleeding); VWF levels depend on genetic and non-genetic factors affecting diagnosis and clinical expression. The inheritance can be autosomal, dominant or recessive according to the variants. To reach diagnosis, several tests are required, being some of them unspecific. The laboratory testing begins with global tests, followed by confirmatory tests and further tests to define the variant of VWD. Genotypic studies are essential to achieve the differential diagnosis between VWD2B vs. PT-VWD, VWD2N vs. Hemophilia A (mild to moderate) and differentiate VWD from AVWS and discriminate VWD2 variants.

O fator de von Willebrand (vWF) é uma glicoproteína sintetizada em células endoteliais e em megacariócitos. Sua vida média é de ~12 horas. É constituído por multímeros de pesos moleculares diferentes, pequenos, intermediários, grandes e extragrandes. A atividade funcional reside nos multímeros grandes, sendo os extragrandes, trombogênicos. Promove adesão das plaquetas ao subendotélio, a agregação plaquetária e transporta o FVIII em plasma, protegendo-o de sua degradação. A doença de von Willebrand é o distúrbio hemorrágico mais frequente; são descritas deficiências quantitativas (parcial: VWD1; total: VWD3) ou defeitos qualitativos (VWD2A, VWD2M, VWD2B e VWD2N). A expressão clínica é variável, (sangramento mucocutâneo), e sua herança autossômica dominante ou recessiva de acordo com as variantes. Os níveis de vWF dependem de fatores genéticos e não-genéticos que afetam o diagnóstico e a expressão clínica. Para fazer o diagnóstico, vários testes são necessários, alguns inespecíficos. O laboratório começa com testes orientadores, continua com testes de confirmação e, mais tarde, com testes para definir a variante de VWD. O diagnóstico genotípico é essencial para alcançar o diagnóstico diferencial entre VWD2B vs. PT-VWD e VWD2N vs. Hemofilia A (leve a moderada), diferenciar VWD de AVWS, discriminar variantes VWD2.

Inhibidores adquiridos de la coagulación: enfoque diagnóstico y casos especiales / Acquired inhibitors of blood coagulation: diagnostic perpective and especial cases / Inibidores adquiridos da coagulação: abordagem diagnóstica e casos especiais

Los inhibidores adquiridos son defectos raros. Se asocian a diferentes manifestaciones clínicas con morbimortalidad significativa. Su detección es importante para implementar el tratamiento sin demora. Hay inhibidores específicos (bloquean función), contra todos los factores de la coagulación y además VWF, o de interferencia (afectan una o varias vías de la coagulación). Los inhibidores específicos son alo-anticuerpos desarrollados en pacientes deficitarios (complicación terapéutica) o auto-anticuerpos presentes en individuos sin alteraciones previas. Hay anticuerpos específicos que pueden afectar la depuración pero no inhiben función. Inhibidores de interferencia: inmunoglobulinas u otras sustancias (heparina/heparinoides, PDF/pdf, PIVKAS, moléculas anómalas, etc.) asociadas a diferentes situaciones clínicas (asintomáticos, sangrados, trombosis y/o complicaciones obstétricas). El laboratorio es fundamental para el diagnóstico. Las pruebas globales detectan el defecto, que no corrigen por el agregado de plasma normal; se caracteriza luego el tipo de inhibidor y eventualmente se titula. Esto es complejo; hay variabilidad en los resultados y posibilidad de falsos positivos o negativos, además las pruebas no son estrictamente específicas. Los algoritmos diagnósticos son útiles, pero no contemplan la posibilidad de defectos combinados. Es crítico caracterizar al inhibidor y descartar posibles interferencias o defectos concomitantes; ello requiere aplicar las pruebas adecuadas e interpretarlas correctamente.

Acquired inhibitors are rare disorders. They are associated with different clinical behaviours and significant morbi-mortality. Detection is important in order to start treatment urgently. There are either specific inhibitors, which block function, against all coagulation factors, and VWF, or with interference effects, on one or more coagulation pathways. Specific inhibitors are either allo-antibodies developed in deficient patients, which give rise to therapeutic complication; or auto-antibodies, which are present in individuals without previous defects. There are specific antibodies that can affect clearance but which cannot block the function. Inhibitors with interference effects are immunoglobulins or other substances (heparin/heparinoids, FDP/fdp, PIVKAS, abnormal molecules, etc.) associated with different clinical settings (asymptomatic, bleeding, thrombosis and/or obstetric complications). Laboratory results are fundamental for the diagnosis. Global tests are able to detect the defect, which is not corrected by the addition of normal plasma; the type of inhibitor is then characterized and titration of the inhibitor is eventually performed. This is complex; there is variability in the results and there is likelihood of false positive or negative results; moreover, the tests are not strictly specific. Diagnostic algorithms are useful tools but they do not consider combined defects. It is a critical point to characterize the inhibitor and exclude possible interferences or concomitant defects; this demands application of the correct tests without misinterpretations.

Os inibidores adquiridos são defeitos raros. Associam-se a diferentes manifestações clínicas com morbimortalidade significativa. Sua detecção é importante para implementar o tratamento sem demora. Há inibidores específicos (bloqueiam função), contra todos os fatores da coagulação e também VWF, ou de interferência (afetam uma ou várias vias da coagulação). Inibidores específicos: - aloanticorpos desenvolvidos em pacientes deficitários (complicação terapêutica); - autoanticorpos, em indivíduos sem alterações prévias. Existem anticorpos específicos que podem afetar a depuração, mas não inibem função. Inibidores de interferência: imunoglobulinas ou outras substâncias (heparina/heparinoides, PDF/pdf, PIVKAS, moléculas anômalas, etc.) associadas a diferentes situações clínicas (assintomáticos, sangramentos, tromboses e/ou complicações obstétricas). O laboratório é fundamental para o diagnóstico. Os testes globais detectam o defeito, que não corrige pelo acréscimo de plasma normal; caracteriza-se depois o tipo de inibidor e eventualmente é titulado. Isto é complexo; há variabilidade nos resultados e possibilidade de falsos positivos ou negativos, além disso os testes não são rigorosamente específicos. Os algoritmos diagnósticos são úteis, mas não consideram a possibilidade de defeitos combinados. É crítico caracterizar o inibidor e descartar possíveis interferências ou defeitos concomitantes; isso requer aplicar os testes adequados e interpretá-los corretamente.

Inhibidor lúpico en situaciones clínicas diferentes al síndrome antifosfolipídico / Lupus inhibitor in clinical situations other than antiphospholipid syndrome

El inhibidor lúpico (IL) es uno de los criterios de laboratorio para Síndrome Antifosfolipídico (SAF); sin embargo, puede detectarse en individuos asintomáticos o estar asociado a otras situaciones clínicas. Presentamos un análisis retrospectivo de 1000 exámenes consecutivos para IL (TTPA, DRVVT) de los cuales 249 casos no presentaban criterios clínicos de SAF. Aplicando los criterios SSC-ISTH, hallamos IL+ en 27,30% (205/751) y 43,37% (108/249) de los casos con y sin criterios clínicos de SAF respectivamente; analizándose en estos últimos casos las características clínicas y de laboratorio. Contexto clínico de casos IL+ sin SAF: 18,52% asintomáticos, 34,26% síntomas de sangrado y 47,22% otras manifestaciones. Otras alteraciones de laboratorio en casos IL+ sin SAF, con síntomas de sangrado: detectamos alteraciones plaquetarias, descenso de VWF:RCo y/o VWF:Ag, disminución de FVIII, FV, FVII, FXI o fibrinógeno e hiperfibrinolisis en el 54,05% de los casos. El análisis mostró detección de IL+ en un número importante de estudios (108/1000) sin criterios SAF. Los casos con IL+ y sangrado representan un desafío particular, al requerir evaluar otros posibles defectos subyacentes, que pudiesen justificar el comportamiento clínico. La detección e identificación de defectos combinados requiriere de un análisis minucioso, a fin de alcanzar un diagnóstico correcto, esencial para tomar decisiones terapéuticas adecuadas. (AU)

Despite lupus anticoagulant (LA) is one of the laboratory criteria for antiphospholipid syndrome (APS), it can be present in asymptomatic subjects or it can be associated with other clinical settings. We present a retrospective analysis of 1000 consecutive LA assays (APTT, DRVVT), 249 of them were performed in patients without clinical criteria for APS. According to ISTH criteria, positive LA was found in 27.30% (205/751) and 43.37% (108/249) of cases with or without APS criteria respectively; in the last group, the analysis of clinical background and laboratory characteristics was done. Clinical background of LA+ cases without APS: 18.52% asymptomatic, 34.26% bleeding symptoms and 47.22% other clinical settings. Other abnormal laboratory tests in LA+ cases without APS and bleeding symptoms: platelet dysfunction; low VWF:RCo and/or VWF:Ag; decrease of FVIII, FV, FVII, FXI or fibrinogen and hyperfibrinolysis were found in the 54.05% of the cases. The analysis showed positive LA in an important number of cases (108/1000) without criteria of APS. Those LA+ cases with bleeding symptoms represent a particular challenge because other possible underlying defects have to be analysed in order to explain the clinical behaviour. The detection and identifications of combined defects required a careful analysis in order to achieve accurate diagnosis, essential for therapeutic decisions. (AU)

Resilient women: from victimhood to autonomy. Case study in the self-help groups codependent anonymous / La mujer resiliente: de víctima a responsable. Estudio de casos en los grupos de autoayuda codependientes anónimos / A mulher resiliente: de vítima a responsável. Estudo de casos nos grupos de autoajuda codependentes anônimos

This work focuses on highlighting the resilience developed by the women interviewed about the violence they were subjected and on observing the new life conditions that they wanted to develop grounded in their reality. This analysis belongs to the field of social sciences and psychology since it describes resilience, a phenomenon addressed by both disciplines. The hypothesis proposes that through the active belonging to the self-help groups Codependent Anonymous, women who have experienced violence can distance themselves from the problem and develop a sense of responsibility for their own lives. From a gender point of view, this research finds its justification in the category of gender oppression, formulated by Marcela Lagarde on her work entitled "Women captivities." In the field of personality theory, the explanation of interaction dynamics in codependent relationships is sustained through Transactional Analysis, based on Gloria Noriega Gayol's research on codependence and its relation with transgenerational roles. In order to give a sociological explanation of codependence as a phenomenon, Pierre Bourdieu's theory of fields has been applied and codependence has been defined as a habitus. This work shows the way some women participating in Codependent Anonymous self-help groups, were able to achieve a higher level of consciousness through the training offered by these groups and were able to choose strategies that enabled them to face their life situation more centred in themselves while taking responsibility for their lifestyle choice.

Este trabajo se centra en destacar la resiliencia que desarrollaron las mujeres entrevistadas a partir de la violencia de la que fueron objeto y en observar las nuevas condiciones de vida que se plantearon, fundamentadas en su realidad. Se inserta en el campo de las ciencias sociales y el de la psicología, toda vez que describe la resiliencia, un fenómeno que compete a ambos campos. La hipótesis plantea que, a través de la militancia en los grupos de autoayuda Codependientes Anónimos, algunas mujeres que han experimentado violencia, pueden lograr un auto-distanciamiento que les permita desarrollar la responsabilidad sobre sus propias vidas. Desde una visión de género, encuentra su justificación en la categoría opresión de género, planteada por Marcela Lagarde en su trabajo "Los Cautiverios de las Mujeres." En el campo de las Teorías de la Personalidad, desde el Análisis Transaccional, plantea la dinámica de interacción presente en las relaciones codependientes basada en la investigación de Gloria Noriega Gayol acerca de los roles transgeneracionales. Para dar una explicación sociológica de la codependencia como un fenómeno, se ha aplicado la Teoría de Campos de Pierre Bourdieu, y se ha definido a la Codependencia como un hábitus. La conclusión presenta la forma en la que algunas mujeres participantes en los grupos de auto-ayuda Codependientes Anónimos, incrementaron su nivel de consciencia a partir del entrenamiento provisto en estos grupos y eligieron estrategias para enfrentar su situación de vida desde una postura más centrada en ellas mismas y haciéndose responsables de su forma de vivir.

Este trabalho se centra em destacar a resiliência que mulheres entrevistadas desenvolveram a partir da violência à que foram objetos e em observar as novas condições de vida propostas, fundamentadas na sua realidade. Insere-se na área das ciências sociais e da psicologia, já que descreve a resiliência, um fenômeno que compete a ambos campos. A hipótese propõe que, através da militância nos grupos de autoajuda Codependentes Anônimos, algumas mulheres que sofreram violência, podem conseguir um autodistanciamento que lhes permita desenvolver a responsabilidade sobre suas próprias vidas. Desde uma visão de gênero, encontra sua justificação na categoria opressão de gênero, proposta por Marcela Lagarde no seu trabalho "Os Cativeiros das Mulheres." No campo das Teorias da Personalidade, desde a Análise Transacional, propõe a dinâmica de interação presente nas relações codependentes baseada na pesquisa de Gloria Noriega Gayol sobre os papéis trans-geracionais. Para dar una explicação sociológica da codependência como um fenômeno, foi aplicada a Teoria de Campos de Pierre Bourdieu, e definiu-se a Codependência como um hábitus. A conclusão apresenta a forma em que algumas mulheres participantes dos grupos de autoajuda Codependentes Anônimos, aumentaram seu nível de consciência a partir do treinamento provisto nestes grupos e escolheram estratégias para enfrentar sua situação de vida desde una postura mais centrada em si mesmas, fazendo-se responsáveis da sua forma de viver.

Vitamina K epóxido reductada (VKORC1): polimorfismos y sensibilidad a los dicumarínicos / Vitamin K epoxide reductase (VKORC1): polimorphisms and sensitivity to coumarin

Introducción: Los antagonistas de la vitamina K, tienen como blanco el complejo vitamina K epóxido reductasa. Hay polimorfismos (SNPs) en el gen de la subunidad 1 (VKORC1), como 1173 C>T (rs9934438) (intrón 1) y -1639 G>A (rs9923231) (región 3'UTR), asociados con diferente sensibilidad a los dicumarínicos. Objetivo: confirmar la relación entre estos SNPs y la dosis media requerida para una correcta anticoagulación. Material y Método: Estudiamos 102 pacientes (15-87 años) bajo tratamiento anticoagulante oral crónico, principalmente acenocumarol. La genotipificación fue realizada usando RFLPs (amplificación del ADN por PCR, seguida por digestión con Msp I para -1639 G>A y Sty I para 1173 C>T); analizándose luego la dosis media en los portadores de los diferentes SNPs. La frecuencia alélica obtenida para 1173 C>T fue similar a la calculada para -1639 G>A, observándose que 1179 C>T y -1639 G>A se hallan en desequilibrio de unión. La dosis media fue más alta en los pacientes portadores hemocigotos del alelo 1173 CC o -1639 GG que en los no portadores. La dosis media fue menor en individuos mayores de 70 años, independientemente de su genotipo. Reultados: Estos confirman la relación entre los SNPs analizados y la dosis de dicumarínicos.

Vitamin K epoxide reductase complex is the target of Vitamin K antagonists. Polymorphism (SNPs) in the gene of subunit 1 (VKORC1), 1173 C>T (rs9934438) (intrón 1) y -1639 G>A (rs9923231) (3'UTR), are associated with different sensitivity to oral anticoagulants. Objectives: our aim was to comfirm the relationship between these SNPs and the mean dose required for anticoagulation. Material and methods: One hundred and two patients (15-87 years) on chronic oral anticoagulant therapy, mainly acenocoumarol, were tested. Genotyping was performed using RFLPs (DNA's PCR amplification, followed by digestion with Msp I to Sty I to 1173 C>T). The mean dose of anticoagulantin carriers of different SNPs was calculated. A similar allelic frequency was obtained for 1173 C>T and -1639 G>A with linkage desequilibrium between them. The mean dose was higher in patients homozygous for 1173 CC or -1639 GG alleles than in non carriers. In those individuals over the age of 70, regardless of genotype, a lower mean dose was observed. Results: The results confirm the relationship between SNPs and oral anticoagulants.

Vitamina K epóxido reductada (VKORC1): polimorfismos y sensibilidad a los dicumarínicos / Vitamin K epoxide reductase (VKORC1): polimorphisms and sensitivity to coumarin

Introducción: Los antagonistas de la vitamina K, tienen como blanco el complejo vitamina K epóxido reductasa. Hay polimorfismos (SNPs) en el gen de la subunidad 1 (VKORC1), como 1173 C>T (rs9934438) (intrón 1) y -1639 G>A (rs9923231) (región 3UTR), asociados con diferente sensibilidad a los dicumarínicos. Objetivo: confirmar la relación entre estos SNPs y la dosis media requerida para una correcta anticoagulación. Material y Método: Estudiamos 102 pacientes (15-87 años) bajo tratamiento anticoagulante oral crónico, principalmente acenocumarol. La genotipificación fue realizada usando RFLPs (amplificación del ADN por PCR, seguida por digestión con Msp I para -1639 G>A y Sty I para 1173 C>T); analizándose luego la dosis media en los portadores de los diferentes SNPs. La frecuencia alélica obtenida para 1173 C>T fue similar a la calculada para -1639 G>A, observándose que 1179 C>T y -1639 G>A se hallan en desequilibrio de unión. La dosis media fue más alta en los pacientes portadores hemocigotos del alelo 1173 CC o -1639 GG que en los no portadores. La dosis media fue menor en individuos mayores de 70 años, independientemente de su genotipo. Reultados: Estos confirman la relación entre los SNPs analizados y la dosis de dicumarínicos. (AU)

Vitamin K epoxide reductase complex is the target of Vitamin K antagonists. Polymorphism (SNPs) in the gene of subunit 1 (VKORC1), 1173 C>T (rs9934438) (intrón 1) y -1639 G>A (rs9923231) (3UTR), are associated with different sensitivity to oral anticoagulants. Objectives: our aim was to comfirm the relationship between these SNPs and the mean dose required for anticoagulation. Material and methods: One hundred and two patients (15-87 years) on chronic oral anticoagulant therapy, mainly acenocoumarol, were tested. Genotyping was performed using RFLPs (DNAs PCR amplification, followed by digestion with Msp I to Sty I to 1173 C>T). The mean dose of anticoagulantin carriers of different SNPs was calculated. A similar allelic frequency was obtained for 1173 C>T and -1639 G>A with linkage desequilibrium between them. The mean dose was higher in patients homozygous for 1173 CC or -1639 GG alleles than in non carriers. In those individuals over the age of 70, regardless of genotype, a lower mean dose was observed. Results: The results confirm the relationship between SNPs and oral anticoagulants. (AU)

Diagnosis and management of von Willebrand disease in a single institution of Argentina.

Von Willebrand disease (VWD) is a bleeding disorder with variable clinical expression. In this article we describe types, clinical features, genetic testing when needed, genotype/phenotype relationships, and the response to desmopressin (DDAVP) testing, according to our experience. Our findings are possible type 1, 69.6%; type 1, 13.5%; severe type 1, 0 .35%; type 3, 0.55%; type 2A, 9.5%; probable 2B, 0.6%; type 2M, 2.5%; and probable type 2N, 3.4%. The most frequent symptoms are ecchymoses-hematomas and epistaxis, and, in females >over 13 years also menorrhagia. In pregnant patients, assessment of laboratory parameters in months 7 and 8 is recommended to plan the need for prophylaxis at term. DDAVP merits to be considered as the first-choice therapy, including pregnant women and children, and no patient showed significant unwanted effects. Because this is a safe, effective, and affordable therapy, we hope to encourage clinicians, mainly pediatricians and obstetricians, to a wider use of DDAVP, especially in developing countries. We also report two patients with prophylactic treatment.

Hemorragias mayores asociadas a cirugía en pacientes con enfermedad de Von Willebrand leve / Major haemorrhages associated with surgery in patients with mild von Willebrand disease

Introducción: Los pacientes con enfermedad de von Willebrand frecuentemente sangran frente a desafíos hemostáticos. Objetivos: Nuestro propósito fue identificar marcadores predictivos de hemorragia mayor en cirugías en pacientes con las variantes tipo 1 y posible tipo 1 de la enfermedad. Material y Métodos: Se registraron las hemorragias mayores en cirugías anteriores al diagnóstico y los parámetros de laboratorio en 311 pacientes. Éstos se agruparon de acuerdo con la ausencia (grupo A) o presencia (grupo B) de hemorragia mayor en cirugías. Resultados: Presentaron hemorragia mayor el 26 por ciento de los pacientes y 17,5 por ciento de las cirugías. No hubo diferencias en el porcentaje de pacientes tipo 1 (32,6 por ciento) y posible tipo 1 (24,8 por ciento) que tuvieron hemorragia mayor. Tampoco se observaron diferencias en la prevalencia del grupo sanguíneo O, edad, género, historia familiar y niveles de FVIII y VW entre los grupos A y B. La hemorragia post exodoncia fue el antecedente clínico más frecuente (P<0,000; RR=2,11; IC 95 por ciento = 1,3-3,5) y podría definir riesgo de hemorragias mayores. El bleeding score y el número de sitios de sangrado no resultaron predictivos de hemorragias mayores. Las cesáreas (24,6 por ciento) y adenoamigdalectomías (22,3 por ciento) fueron las cirugías con mayor frecuencia de hemorragias mayores. Conclusión: Los pacientes con VWD tipo 1 y posible tipo 1 mostraron similar incidencia de hemorragia mayor en cirugías. Los niveles de FVIII y VWF, el tiempo de sangría, historia familiar y grupo sanguíneo no resultaron efectivos como marcadores predictivos de hemorragia mayor. Sin embargo, el antecedente de sangrado post exodoncia y el tipo de cirugía a llevar a cabo (cesáreas y adenoamigdalectomías) en pacientes con enfermedad de von Willebrand tipo 1 y posible tipo 1 parecen importantes como marcadores de riesgo.

Introduction: Patients with von Willebrand disease frequently bleed under haemostatic challenges. Objectives: The aim of our study was to identify predictive markers of perioperative major haemorrhage in type 1 and possible type 1 patients von Willebrand disease. Material and Methods: We recorded perioperative bleeding complications previous to diagnosis and laboratory parameters in 311 patients. They were grouped according to the absence (group A) or presence (group B) of perioperative major haemorrhage. Results: Twenty-six per cent of patients and 17.5 per cent of surgical procedures presented major haemorrhage. There was no difference neither between percentages of type 1 (32.6 per cent) and possible type 1 patients (24.8 per cent) who had major haemorrhage nor in the prevalence of O blood group, age, gender, family history and levels of FVIII and VWF, between group A and B. A history of bleeding after tooth extraction was the most frequent clinical feature (P<0.000; RR=2.11; CI 95 per cent = 1.3-3.5) observed in patients with major haemorrhage, and could defi ne risk factor. The bleeding score and the number of bleeding sites were not predictors of major haemorrhages. Caesarean sections (24.6 per cent) and adeno-tonsillectomies (22.3 per cent) showed the highest frequency of major haemorrhage. Conclusion: Type 1 and possible type 1 VWD patients showed similar incidence of perioperative major haemorrhage. The levels of FVIII and VWF, the bleeding time, blood group and family history did not prove to be effective as predictive markers of major haemorrhage. However, the personal history of bleeding after tooth extraction and the type of surgery (caesarean section and adeno-tonsillectomies) in patients with either type 1 or possible type 1 von Willebrand disease shown to be important in determining risk.

Biological and clinical response to desmopressin (DDAVP) in a retrospective cohort study of children with low von Willebrand factor levels and bleeding history.

The diagnosis and management of von Willebrand disease (VWD) in paediatrics is challenging. Our aim was to review patient's characteristics related to biological and clinical response to DDAVP in children with low von Willebrand factor (VWF) levels and bleeding history from a single institution. We included a retrospective cohort of 221 children (median age 11 years; 137 females): 27 type 1 (VWF levels within 15-30 IU dL-1) and 194 possible type 1 (VWF levels within 31-49 IU dL-1). The DDAVP infusion-test was performed in 214/221 children, 93.4% of whom showed good response. Patients with type 1 were at higher risk of DDAVP-test failure: 9/26 (34.6%) vs. 18/188 (9.6%) with possible type 1 (RR 3.44, 1.75-6.79; p= 0.002, Fisher's exact test). In 68 children, the clinical response to DDAVP was evaluated 87 times: i) to stop bleeding: menorrhagia (13), mucocutaneous (12), haemarthrosis (1); and ii) to prevent surgical bleeding: adenotonsillectomy (17), major (15) and minor surgery (10); and dental procedures (19). No major adverse events or bleeding were observed. The treatment was effective with one single dose of DDAVP in almost all patients, without antifibrinolytic or local therapy, except in a girl with severe haemorrhage during menarche who required replacement therapy. In conclusion, patients with VWD type 1 were at higher risk of no response to DDAVP infusion-test. In this series, one dose of DDAVP proved effective and safe for children with VWD. Since this is a safe, effective and affordable therapy, we consider that a wider use should be promoted, especially in developing countries.

La salud emocional: qué es y cómo alcanzarla

Contenido: La respuesta emocional. Inteligencia y salud emocional. El universo afectivo. Sentimientos y pasiones. La expresión de las emociones. El lenguaje corporal de las emociones. La postura corporal. El sustrato orgánico de la emoción. Enojo. Estrategias para neutralizar la ira. Tristeza. Estrategias para elaborar las pérdidas. Miedo. Estrategias para el alivio del estrés. Alegría...

La salud emocional: qué es y cómo alcanzarla

Contenido: La respuesta emocional. Inteligencia y salud emocional. El universo afectivo. Sentimientos y pasiones. La expresión de las emociones. El lenguaje corporal de las emociones. La postura corporal. El sustrato orgánico de la emoción. Enojo. Estrategias para neutralizar la ira. Tristeza. Estrategias para elaborar las pérdidas. Miedo. Estrategias para el alivio del estrés. Alegría...(AU)

Major haemorrhage related to surgery in patients with type 1 and possible type 1 von Willebrand disease.

Patients with von Willebrand disease (VWD) frequently bleed under a challenge. The aim of our study was to identify predictive markers of perioperative major haemorrhage in type 1 (VWF:RCo = 15-30 IU dl(-1)) and possible type 1 (VWF:RCo = 31-49 IU dl(-1)) VWD patients. We recorded perioperative bleeding complications previous to diagnosis and laboratory parameters in 311 patients with 498 surgical procedures. The patients were grouped according to the absence (A) or presence (B) of perioperative major haemorrhages. Eighty-one patients (26%) and 87 surgical procedures (17.5%) presented major haemorrhages associated with surgeries. There was no difference between the percentage of type 1 and possible type 1 VWD patients who had major haemorrhages (32.6% and 24.8% respectively; p = ns). No difference in the prevalence of O blood group, age, gender, positive family history and laboratory test results (FVIII and VWF) was observed, independent of the haemorrhagic tendency. Bleeding after tooth extraction was the most frequent clinical feature observed in patients with perioperative major haemorrhages. The bleeding score and the number of bleeding sites (> or = 3) were not predictors of major haemorrhage associated with surgery. Caesarean section and adenotonsillectomy showed the highest frequency of major haemorrhages (24.6% and 22.3%, respectively). In conclusion, type 1 and possible type 1 VWD patients showed similar incidence of perioperative major haemorrhages. Laboratory tests and positive family history did not prove to be effective at predicting major haemorrhages in patients that had either type 1 or possible type 1 VWD. The history of bleeding after tooth extraction could define risk factors of major haemorrhage.

Por qué nos enfermamos: guía holística para vivir mejor

Contenido: La salud holística. Actividad: en el aquí y el ahora. El cuerpo. La mente. Actividad: la capacidad de afrontamiento. Las emociones. Actividad: emociones cotidianas. El espíritu. Actividades: valores y sentido. Nuestro mundo de relaciones. Actividades: las relaciones. Coherencia y congruencia. Actividad: la salud holística. Los gritos y susurros del cuerpo...