2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19.

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

[How to generate recommendations for venous thromboprophylaxis in health institutions?] / Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud.

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panamena de Hematología, Sociedad Peruana de Hematología, and SVH 2023 guidelines for diagnosis of venous thromboembolism and for its management in special populations in Latin America.

Implementation of international guidelines in Latin American settings requires additional considerations (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The purpose of this guideline is to provide evidence-based recommendations about the diagnosis of venous thromboembolism (VTE) and its management in children and during pregnancy. We used the GRADE ADOLOPMENT method to adapt recommendations from 3 American Society of Hematology (ASH) VTE guidelines (diagnosis of VTE, VTE in pregnancy, and VTE in the pediatric population). ASH and 12 local hematology societies formed a guideline panel comprising medical professionals from 10 countries in Latin America. Panelists prioritized 10 questions about the diagnosis of VTE and 18 questions about its management in special populations that were relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context. In comparison with the original guideline, there were significant changes in 2 of 10 diagnostic recommendations (changes in the diagnostic algorithms) and in 9 of 18 management recommendations (4 changed direction and 5 changed strength). This guideline ADOLOPMENT project highlighted the importance of contextualizing recommendations in other settings based on differences in values, resources, feasibility, and health equity impact.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, Sociedad Peruana de Hematología, and SVH 2022 guidelines for prevention of venous thromboembolism in surgical and medical patients and long-distance travelers in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementation of international guidelines in Latin American settings requires additional considerations. OBJECTIVE: To provide evidence-based guidelines about VTE prevention for Latin American patients, clinicians, and decision makers. METHODS: We used the GRADE ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Prevention of VTE in Surgical Patients and Prophylaxis for Medical Patients). ASH and 12 local hematology societies formed a guideline panel composed of medical professionals from 10 countries in Latin America. Panelists prioritized 20 questions relevant to the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context, that is, values and preferences, resources, accessibility, feasibility, and impact on health equity. RESULTS: The panel agreed on 21 recommendations. In comparison with the original guideline, 6 recommendations changed direction and 4 recommendations changed strength. CONCLUSIONS: This guideline ADOLOPMENT project highlighted the importance of contextualization of recommendations in other settings, based on differences in values, resources, feasibility, and health equity impact.

[MANAGEMENT RECOMMENDATIONS FOR DIRECT ORAL ANTICOAGULANTS (DOACs) ANTI Xa AND ANTI IIa]. / RECOMENDACIONES DE MANEJO DE LOS ANTICOAGULANTES ORALES DIRECTOS (DOACS) ANTI Xa Y ANTI IIa.

Direct oral anticoagulants have emerged as the drugs that have changed the management of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagulants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas propiedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Methodology for adaptation of the ASH Guidelines for Management of Venous Thromboembolism for the Latin American context.

BACKGROUND: From 2017 to 2020, the American Society of Hematology (ASH) collaborated with 12 hematology societies in Latin America to adapt the ASH guidelines on venous thromboembolism (VTE). OBJECTIVE: To describe the methods used to adapt the ASH guidelines on venous thromboembolism. METHODS: Each society nominated 1 individual to serve on the guideline panel. The work of the panel was facilitated by the 2 methodologists. The methods team selected 4 of the original VTE guidelines for a first round. To select the most relevant questions, a 2-step prioritization process was conducted through an on-line survey and then through in-person discussion. During an in-person meeting in Rio de Janeiro, Brazil, from 23 April through 26 April 2018, the panel developed recommendations using the ADOLOPMENT approach. Evidence about health effects from the original guidelines was reused, but important data about resource use, accessibility, feasibility, and impact in health equity were added. RESULTS: In the guideline accompanying this paper, Latin American panelists selected 17 questions from an original pool of 49. Of the 17 questions addressed, substantial changes were introduced for 5 recommendations, and remarks were added or modified for 12 recommendations. CONCLUSIONS: By using the evidence from an international guideline, a significant amount of work and time were saved; by adding regional evidence, the final recommendations were tailored to the Latin American context. This experience offers an alternative to develop guidelines relevant to local contexts through a global collaboration.

ASH, ABHH, ACHO, Grupo CAHT, Grupo  CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, SPH, and SVH 2021 guidelines for management of venous thromboembolism in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelinn Aes in Latimerican settings requires additional considerations. OBJECTIVE: The purpose of our study was to provide evidence-based guidelines about managing VTE for Latin American patients, clinicians, and decision makers. METHODS: We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)-ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Treatment of VTE and Anticoagulation Therapy). ASH and local hematology societies formed a guideline panel comprised of medical professionals from 10 countries in Latin America. Panelists prioritized 18 questions relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). RESULTS: The panel agreed on 17 recommendations. Compared with the original guideline, 4 recommendations changed direction and 1 changed strength. CONCLUSIONS: This guideline adolopment project highlighted the importance of contextualization of recommendations suggested by the changes to the original recommendations. The panel also identified 2 implementation priorities for the region: expanding the availability of home treatment and increasing the availability of direct oral anticoagulants (DOACs). The guideline panel made a conditional recommendation in favor of home treatment for individuals with deep venous thrombosis and a conditional recommendation for either home or hospital treatment for individuals with pulmonary embolism. In addition, a conditional recommendation was made in favor of DOACs over vitamin K antagonists for several populations.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

Gramicidin S derivatives containing cis- and trans-morpholine amino acids (MAAs) as turn mimetics.

The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D-Phe-Pro two-residue turn motifs in the rigid cyclic beta-hairpin structure of GS was replaced with morpholine amino acids (MAA 2-5), differing in stereochemistry and length of the side-chain. The conformational properties of the thus obtained GS analogues (6-9) was assessed by using NMR spectroscopy and X-ray crystallography, and correlated with their biological properties (antimicrobial and hemolytic activity). We show that compound 8, containing the dipeptide isostere trans-MAA 4, has an apparent high structural resemblance with GS and that its antibacterial activity against a panel of Gram positive and -negative bacterial strains is better than the derivatives 6, 7 and 9.

[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.

Pilot study of homocysteine and cysteine in patients with thrombosis in different vascular sites. Epidemiology and response to folate.

Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis. However, lowering homocysteine (Hcy) with vitamins not only failed to improve outcomes but also may lead to recurrent events. Our objectives were to evaluate Hcy and cysteine (Cys) levels in patients with thrombosis in different vascular sites, and their response to folate. One hundred and sixty four consecutive patients with thrombosis (42.1% arterial (AT), 36% venous (VT), 4.9% both venous and arterial thrombosis (AVT) and 17% unusual site (UST)) were included. Hcy and Cys were highest in patients with AVT and UST (p=0.0006). Ninety-three patients were treated, 70% were followed-up. Hcy levels normalized after therapy in all patients. Cys levels tended to vary after therapy according to the site of thrombosis. We observed a significant correlation between folate and Hcy (r: 0.48; p=0.005) among homozygous for MTHFR. A significant inverse relation was observed between Hcy and folate among homozygous and heterozygous (r: 0.462, p=0.007 and r: 0.267; p=0.04, respectively). No correlation was observed between folate and Cys. In conclusion, our observations suggest that Hcy and Cys might be implicated in thrombosis in different vascular sites, and respond differently to folate.

Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud / How to generate recommendations for venous thromboprophylaxis in health institutions?

Resumen La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

Abstract Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital´s reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panamena de Hematología, Sociedad Peruana de Hematología, and SVH 2023 guidelines for diagnosis of venous thromboembolism and for its management in special populations in Latin America

Implementation of international guidelines in Latin American settings requires additional considerations (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The purpose of this guideline is to provide evidence-based recommendations about the diagnosis of venous thromboembolism (VTE) and its management in children and during pregnancy. We used the GRADE ADOLOPMENT method to adapt recommendations from 3 American Society of Hematology (ASH) VTE guidelines (diagnosis of VTE, VTE in pregnancy, and VTE in the pediatric population). ASH and 12 local hematology societies formed a guideline panel comprising medical professionals from 10 countries in Latin America. Panelists prioritized 10 questions about the diagnosis of VTE and 18 questions about its management in special populations that were relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context. In comparison with the original guideline, there were significant changes in 2 of 10 diagnostic recommendations (changes in the diagnostic algorithms) and in 9 of 18 management recommendations (4 changed direction and 5 changed strength). This guideline ADOLOPMENT project highlighted the importance of contextualizing recommendations in other settings based on differences in values, resources, feasibility, and health equity impact.

Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti Xa y anti IIa / Recommendations for the practical management of the direct oral anticoagulants anti Xa and anti IIa

Resumen Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas pro piedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Abstract Direct oral anticoagulants have emerged as the drugs that have changed the man agement of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagu lants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease.

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.

NETosis before and after Hyperglycemic Control in Type 2 Diabetes Mellitus Patients.

INTRODUCTION AND OBJECTIVE: Diabetes is characterized by chronic inflammation, endothelial dysfunction, increased risk of infections and early cardiovascular disease. By releasing neutrophil extracellular traps (NETs), neutrophils kill bacteria and exert pro-inflammatory and pro-thrombotic activities. Increased NETosis has been found in cross-sectional studies including treated type 2 diabetes mellitus (T2DM) patients. In this study, we determined whether the ability of neutrophils to form NETs differs in diabetic patients pre- and post-hyperglycemic control versus healthy donors (HD), and the relationship between NETosis with pro-thrombotic, pro-inflammatory biomarkers and thrombotic clinical events. METHODS: Diabetic patients recently diagnosed and after 6 and 12 months of treatment (N = 25) and HD (N = 25) were included. NET formation was studied by microscopy and fluorometry. Nucleosomes, HNE-DNA complexes, von Willebrand factor (vWF), IL6 and TNFα plasma levels were measured by ELISA and P-selectin on the platelet surface was assessed by cytometry. RESULTS: Basal levels of NETs in recently diagnosed T2DM patients were higher compared to HD. While TNFα stimulation of control neutrophils resulted in DNA release, patient neutrophils were not responsive. Although glycemia decreased after 6 months of metformin treatment, basal and TNFα and PMA-stimulated NETs reached normal values after 12 months. Compared to controls, nucleosomes, HNE-DNA complexes, IL-6 and TNFα levels were increased in recently diagnosed patients and decreased after 12 months of treatment. P-selectin and vWF levels were similar in both populations. CONCLUSION: Our data suggest that NETs could represent a biomarker for T2DM. Increased NETosis in T2DM patients does not appear to be the consequence of impaired glycemic control but rather due to pro-inflammatory cytokines and is not related to thrombotic events.

ASH, ABHH, ACHO, Grupo CAHT, Grupo  CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, SPH, and SVH 2021: guidelines for management of venous thromboembolism in Latin America

Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelines in Latin American settings requires additional considerations. The purpose of our study was to provide evidence-based guidelines about managing VTE for Latin American patients, clinicians, and decision makers. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)-ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Treatment of VTE and Anticoagulation Therapy). ASH and local hematology societies formed a guideline panel comprised of medical professionals from 10 countries in Latin America. Panelists prioritized 18 questions relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The panel agreed on 17 recommendations. Compared with the original guideline, 4 recommendations changed direction and 1 changed strength. This guideline adolopment project highlighted the importance of contextualization of recommendations suggested by the changes to the original recommendations. The panel also identified 2 implementation priorities for the region: expanding the availability of home treatment and increasing the availability of direct oral anticoagulants (DOACs). The guideline panel made a conditional recommendation in favor of home treatment for individuals with deep venous thrombosis and a conditional recommendation for either home or hospital treatment for individuals with pulmonary embolism. In addition, a conditional recommendation was made in favor of DOACs over vitamin K antagonists for several populations.

Mechanical heart valve prostheses and persistent lupus anticoagulant: is the thrombotic risk increased?

The risk of thrombosis in patients with mechanical heart valve prostheses in spite of life-long adequate anticoagulation is 1-2% per year. Current recommendations for anticoagulation take into account the prosthesis itself and the co-morbid conditions that enhance the thrombotic risk. Lupus anticoagulant is diagnosed in many thrombotic recurrences. We designed an ambispective case-control study to evaluate thrombotic events in patients with mechanical heart valve prostheses and persistent lupus anticoagulant. Our objectives were to determine whether persistent lupus anticoagulant increased the risk of embolism in that population and thus, if a more intense anticoagulation would be recommended, even at the risk of increasing bleeding episodes. We included 16 patients and 16 controls with more than 80 patient-years of follow-up and with other risk factors for embolism. We observed no increased rate of thromboembolic events in patients than in controls, even during high-risk situations (i.e. bacterial endocarditis). Our population spent most of the time within the intended anticoagulation range. We conclude that adequate anticoagulation is the most important issue to prevent events, protecting against thrombosis without increasing the bleeding risk.