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.

[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.

[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.

Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina / Levels of antiplatelet factor 4-heparin antibodies and 4T score for heparin induced thrombocitopenia

La trombocitopenia inducida por heparina (HIT) es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4)-heparina (HPIA). La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica). El índice de las 4T (índice 4T) puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA) que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS). La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001). Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001). Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017). En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.(AU)

Heparin induced thrombocytopenia (HIT) is an immune-mediated disorder due to antibodies anti platelet factor 4-heparin (HPIA). Thrombocytopenia is often moderate but certain patients can develop morbid thrombotic complications. HPIA detection by ELISA has high sensitivity but low specificity, and low titers (without clinical significance) are frequent. A pretest clinical score (4T´s) was developed in order to recognize patients that are at high risk of HIT. The aim of this study was to correlate HPIA levels and the 4T´s score of consecutive patients derived to our center. We evaluated 84 patients (35 of them developed thrombosis); the clinical questionnaire was sent along with the sample and was analyzed by an investigator who did not know the patients´ characteristics, and 4T´s scores were calculated before performing the laboratory tests. HPIA were measured by ELISA (Asserachrom HPIA) that detects IgG, IgM and IgA isotypes, (the only reagent available in our country). 4T´s score correlated with HPIA levels (rho spearman 0.472, p < 0.001). Patients with 4T´s ≥ 6 had higher absorbance percentages than those with ≤ 5 (67 vs. 39%, p < 0.001), and patients with thrombosis also presented higher titers (59 vs. 39%, p = 0.017) than those who did not develop this complication. In conclusion, high titers of HPIA measured by EIA which detects the 3 isotypes, clearly correlate with 4T´s score ≥ 6 and are more frequent in patients who develop thrombosis, just as reported when an IgG specific ELISA is used.(AU)

Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina / Levels of antiplatelet factor 4-heparin antibodies and 4T score for heparin induced thrombocitopenia

La trombocitopenia inducida por heparina (HIT) es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4)-heparina (HPIA). La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica). El índice de las 4T (índice 4T) puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA) que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS). La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001). Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001). Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017). En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.

Heparin induced thrombocytopenia (HIT) is an immune-mediated disorder due to antibodies anti platelet factor 4-heparin (HPIA). Thrombocytopenia is often moderate but certain patients can develop morbid thrombotic complications. HPIA detection by ELISA has high sensitivity but low specificity, and low titers (without clinical significance) are frequent. A pretest clinical score (4T´s) was developed in order to recognize patients that are at high risk of HIT. The aim of this study was to correlate HPIA levels and the 4T´s score of consecutive patients derived to our center. We evaluated 84 patients (35 of them developed thrombosis); the clinical questionnaire was sent along with the sample and was analyzed by an investigator who did not know the patients´ characteristics, and 4T´s scores were calculated before performing the laboratory tests. HPIA were measured by ELISA (Asserachrom HPIA) that detects IgG, IgM and IgA isotypes, (the only reagent available in our country). 4T´s score correlated with HPIA levels (rho spearman 0.472, p < 0.001). Patients with 4T´s ≥ 6 had higher absorbance percentages than those with ≤ 5 (67 vs. 39%, p < 0.001), and patients with thrombosis also presented higher titers (59 vs. 39%, p = 0.017) than those who did not develop this complication. In conclusion, high titers of HPIA measured by EIA which detects the 3 isotypes, clearly correlate with 4T´s score ≥ 6 and are more frequent in patients who develop thrombosis, just as reported when an IgG specific ELISA is used.

Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina / Levels of antiplatelet factor 4-heparin antibodies and 4T score for heparin induced thrombocitopenia

La trombocitopenia inducida por heparina (HIT) es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4)-heparina (HPIA). La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica). El índice de las 4T (índice 4T) puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA) que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS). La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001). Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001). Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017). En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.(AU)

Heparin induced thrombocytopenia (HIT) is an immune-mediated disorder due to antibodies anti platelet factor 4-heparin (HPIA). Thrombocytopenia is often moderate but certain patients can develop morbid thrombotic complications. HPIA detection by ELISA has high sensitivity but low specificity, and low titers (without clinical significance) are frequent. A pretest clinical score (4T´s) was developed in order to recognize patients that are at high risk of HIT. The aim of this study was to correlate HPIA levels and the 4T´s score of consecutive patients derived to our center. We evaluated 84 patients (35 of them developed thrombosis); the clinical questionnaire was sent along with the sample and was analyzed by an investigator who did not know the patients´ characteristics, and 4T´s scores were calculated before performing the laboratory tests. HPIA were measured by ELISA (Asserachrom HPIA) that detects IgG, IgM and IgA isotypes, (the only reagent available in our country). 4T´s score correlated with HPIA levels (rho spearman 0.472, p < 0.001). Patients with 4T´s ≥ 6 had higher absorbance percentages than those with ≤ 5 (67 vs. 39%, p < 0.001), and patients with thrombosis also presented higher titers (59 vs. 39%, p = 0.017) than those who did not develop this complication. In conclusion, high titers of HPIA measured by EIA which detects the 3 isotypes, clearly correlate with 4T´s score ≥ 6 and are more frequent in patients who develop thrombosis, just as reported when an IgG specific ELISA is used.(AU)

[Levels of antiplatelet factor 4-heparin antibodies and 4T score for heparin induced thrombocytopenia]. / Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina.

Heparin induced thrombocytopenia (HIT) is an immune-mediated disorder due to antibodies anti platelet factor 4-heparin (HPIA). Thrombocytopenia is often moderate but certain patients can develop morbid thrombotic complications. HPIA detection by ELISA has high sensitivity but low specificity, and low titers (without clinical significance) are frequent. A pretest clinical score (4T's) was developed in order to recognize patients that are at high risk of HIT. The aim of this study was to correlate HPIA levels and the 4T's score of consecutive patients derived to our center. We evaluated 84 patients (35 of them developed thrombosis); the clinical questionnaire was sent along with the sample and was analyzed by an investigator who did not know the patients' characteristics, and 4T's scores were calculated before performing the laboratory tests. HPIA were measured by ELISA (Asserachrom HPIA) that detects IgG, IgM and IgA isotypes, (the only reagent available in our country). 4T's score correlated with HPIA levels (rho spearman 0.472, p < 0.001). Patients with 4T's = 6 had higher absorbance percentages than those with = 5 (67 vs. 39%, p < 0.001), and patients with thrombosis also presented higher titers (59 vs. 39%, p = 0.017) than those who did not develop this complication. In conclusion, high titers of HPIA measured by EIA which detects the 3 isotypes, clearly correlate with 4T's score = 6 and are more frequent in patients who develop thrombosis, just as reported when an IgG specific ELISA is used.

Current management of antiphospholipid syndrome-related thrombosis.

Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by venous or arterial thrombosis, and recurrent pregnancy morbidity in the presence of antiphospholipid antibodies. Many physicians recommend a daily low dose of aspirin for primary thrombosis prevention in asymptomatic individuals with persistent antiphospholipid antibodies. However, recent data question the effectiveness of aspirin. For the secondary prevention of recurrent thrombosis, the most effective treatment is long-term anticoagulation. A moderate intensity of anticoagulation is recommended in the majority of APS patients. In cases of catastrophic APS, an aggressive therapy is highly recommended using immunosuppression and anticoagulants. This article will also review the experimental evidence of potential therapeutic approaches for the management of APS-related clinical events.

[Chronic thromboembolic pulmonary hypertension with and without antiphospholipid syndrome]. / Hipertension pulmonar tromboembolica cronica con y sin sindrome antifosfolipido.

UNLABELLED: Chronic thromboembolic pulmonary hypertension (CTE-PH) is defined as the chronic obstruction by organized thrombi in pulmonary artery and their branches causing pulmonary hypertension. The objective is to evaluate features and outcome of CTE-PH in patients with and without coexisting antiphospholipid syndrome (APS). All patients studied at our Institution with CTE-PH between June 1993 and June 2005 were analyzed retrospectively. Sixteen out of 38 patients were APS positive (group A), and 22/38 patients (group B) disclosed normal results (n = 10) or other thrombophilic abnormalities (n =12). RESULTS: both groups were similar in age (mean 41 vs. 50 years), NYHA class at diagnosis (81 vs. 100% in III-IV) and the presence of previous or coexistent thrombosis in other territories (31 vs. 27%). Sixty three percent of patients in group A and 55% of patients in group B underwent thromboendarterectomy. The patients were followed during an average of 45 months (0.5-144). At the end of follow up all the APS patients and all the chirurgical patients were in I-II functional class (p=0.053). The median survival from diagnosis was 59 months for group A and 27 months for group B (p=0.199). The mean survival of patients who underwent thromboendarterectomy was 56 months for group A vs. 33 months for group B (p=0.08). We conclude that patients with CTE-PH and APS disclosed a trend to a better survival than patients with CTE-PH without APS. Those patients with CTE-PH and APS who underwent thromboendarterectomy tended to achieve a better functional class and survival than those who received medical treatment.

Hipertension pulmonar tromboembolica cronica con y sin sindrome antifosfolipido / Chronic thromboembolic pulmonary hypertension with and without antiphospholipid syndrome

La hipertensión pulmonar tromboembólica crónica (HPTC) está dada por la obstrucción de arterias pulmonares y sus ramas por trombos organizados. El objetivo fue evaluar las características y evolución de la HPTC en pacientes con y sin síndrome antifosfolípido (SAF). Se analizaron retrospectivamente todos los pacientes con HPTC en nuestra institución entre junio de 1993 y junio del 2005. De los 38 pacientes evaluados, 16 tenían SAF (grupo A) y 22 pacientes (grupo B) presentaban estudio de trombofilia normal (n = 10) u otras anormalidades trombofílicas (n = 12). Ambos grupos fueron similares en cuanto a la media de edad (41 vs. 50 años), la clase funcional que presentaban al diagnóstico (81 vs. 100% en clase III-IV), y la presencia de trombosis en otros territorios (31 vs. 27%). El 62.5% de pacientes del grupo A y el 54.5% del grupo B fueron sometidos a tromboendarterectomía pulmonar. La media de seguimiento fue de 45 meses (rango de 0.5 a 144). Al final del mismo todos los pacientes con SAF y todos los pacientes operados estaban en clase funcional I-II. La mediana de sobrevida desde el momento del diagnóstico alcanzó los 59 meses para el grupo A vs. 27 meses en el grupo B (p = 0.199). La media de sobrevida del total de los pacientes operados fue de 56 meses para el grupo A vs. 33 meses para el grupo B (p = 0.08). En conclusión: Los pacientes con HPTC y SAF tendieron a lograr una mejor sobrevida que los pacientes con HPTC sin SAF. Aquellos con HPTC y SAF que fueron operados lograron mejoría de su clase funcional y tendieron a una mayor sobrevida respecto de los no operados.(AU)

Chronic thromboembolic pulmonary hypertension (CTE-PH) is defined as the chronic obstruction by organized thrombi in pulmonary artery and their branches causing pulmonary hypertension. The objective is to evaluate features and outcome of CTE-PH in patients with and without coexisting antiphospholipid syndrome (APS). All patients studied at our Institution with CTE-PH between June 1993 and June 2005 were analyzed retrospectively. Sixteen out of 38 patients were APS positive (group A), and 22/38 patients (group B) disclosed normal results (n = 10) or other thrombophilic abnormalities (n =12). Results: both groups were similar in age (mean 41 vs. 50 years), NYHA class at diagnosis (81 vs. 100% in III-IV) and the presence of previous or coexistent thrombosis in other territories (31 vs. 27%). Sixty three percent of patients in group A and 55% of patients in group B underwent thromboendarterectomy. The patients were followed during an average of 45 months (0.5- 144). At the end of follow up all the APS patients and all the chirurgical patients were in I-II functional class (p=0.053). The median survival from diagnosis was 59 months for group A and 27 months for group B (p=0.199). The mean survival of patients who underwent thromboendarterectomy was 56 months for group A vs. 33 months for group B (p=0.08). We conclude that patients with CTE-PH and APS disclosed a trend to a better survival than patients with CTE-PH without APS. Those patients with CTE-PH and APS who underwent thromboendarterectomy tended to achieve a better functional class and survival than those who received medical treatment.(AU)

Hipertension pulmonar tromboembolica cronica con y sin sindrome antifosfolipido / Chronic thromboembolic pulmonary hypertension with and without antiphospholipid syndrome

La hipertensión pulmonar tromboembólica crónica (HPTC) está dada por la obstrucción de arterias pulmonares y sus ramas por trombos organizados. El objetivo fue evaluar las características y evolución de la HPTC en pacientes con y sin síndrome antifosfolípido (SAF). Se analizaron retrospectivamente todos los pacientes con HPTC en nuestra institución entre junio de 1993 y junio del 2005. De los 38 pacientes evaluados, 16 tenían SAF (grupo A) y 22 pacientes (grupo B) presentaban estudio de trombofilia normal (n = 10) u otras anormalidades trombofílicas (n = 12). Ambos grupos fueron similares en cuanto a la media de edad (41 vs. 50 años), la clase funcional que presentaban al diagnóstico (81 vs. 100% en clase III-IV), y la presencia de trombosis en otros territorios (31 vs. 27%). El 62.5% de pacientes del grupo A y el 54.5% del grupo B fueron sometidos a tromboendarterectomía pulmonar. La media de seguimiento fue de 45 meses (rango de 0.5 a 144). Al final del mismo todos los pacientes con SAF y todos los pacientes operados estaban en clase funcional I-II. La mediana de sobrevida desde el momento del diagnóstico alcanzó los 59 meses para el grupo A vs. 27 meses en el grupo B (p = 0.199). La media de sobrevida del total de los pacientes operados fue de 56 meses para el grupo A vs. 33 meses para el grupo B (p = 0.08). En conclusión: Los pacientes con HPTC y SAF tendieron a lograr una mejor sobrevida que los pacientes con HPTC sin SAF. Aquellos con HPTC y SAF que fueron operados lograron mejoría de su clase funcional y tendieron a una mayor sobrevida respecto de los no operados.

Chronic thromboembolic pulmonary hypertension (CTE-PH) is defined as the chronic obstruction by organized thrombi in pulmonary artery and their branches causing pulmonary hypertension. The objective is to evaluate features and outcome of CTE-PH in patients with and without coexisting antiphospholipid syndrome (APS). All patients studied at our Institution with CTE-PH between June 1993 and June 2005 were analyzed retrospectively. Sixteen out of 38 patients were APS positive (group A), and 22/38 patients (group B) disclosed normal results (n = 10) or other thrombophilic abnormalities (n =12). Results: both groups were similar in age (mean 41 vs. 50 years), NYHA class at diagnosis (81 vs. 100% in III-IV) and the presence of previous or coexistent thrombosis in other territories (31 vs. 27%). Sixty three percent of patients in group A and 55% of patients in group B underwent thromboendarterectomy. The patients were followed during an average of 45 months (0.5- 144). At the end of follow up all the APS patients and all the chirurgical patients were in I-II functional class (p=0.053). The median survival from diagnosis was 59 months for group A and 27 months for group B (p=0.199). The mean survival of patients who underwent thromboendarterectomy was 56 months for group A vs. 33 months for group B (p=0.08). We conclude that patients with CTE-PH and APS disclosed a trend to a better survival than patients with CTE-PH without APS. Those patients with CTE-PH and APS who underwent thromboendarterectomy tended to achieve a better functional class and survival than those who received medical treatment.

Nadroparine calcium or enoxaparine in acute coronary syndrome patients suffering renal insufficiency: The nadroparin versus enoxaparin (NaVe) study design.

In the general population, mild renal impairment is associated with increases risk for coronary artery disease and stroke, suggesting that cardiovascular disease begins to develop early in the natural history of renal dysfunction. Patients with renal failure are known to be at increased risk of death following acute myocardial infarction or congestive heart failure.In such sense, anticoagulation in addition to antiplatelet inhibitor drugs became the standard of care, particularly, among high risk unstable angina patients associated with a scarce side effects.The Nadroparin calcium Versus Enoxaparin (NaVe) Study will evaluate in a head to head basis the anti Xa activity reached by nadroparine or enoxaparine, both low molecular weight heparins, in patients at high risk for ischemic episodes, and renal insufficiency to eventually be undergone to angiographic diagnosis studies, and in consequence proposing the best anticoagulant strategies for these patients before being invasively treated.Patients will be randomly assigned to one of the two groups: Group 1: thirty patients will be given with subcutaneous enoxaparine injections into the abdominal wall in a dose of 0,85 mg/kg every 12 hours for a maximum of 48 hours. A saline infusion dose will be given in between. Total number of injections: 6. Group 2:Thirty patients will be receiving subcutaneous injections into the abdominal wall in a doses of 30% less in relationship with his / her body weight every 8 hours for a maximum of 48 hours.In order to achieve the goal of the study, the antiXa activity will be measure using venous blood samples taken as follows: Group 1:*Within 3rd and 4 hour of the second doses of HBPM for enoxaparine.*Within 11 th and 12 th hour next to fourth doses of enoxaparine. Group 2: *Within 3rd and 4 th hour next to 3rd doses of HBPM for the nadroparine.*Within 7th and 8th hour next to 4th doses HBPM for the nadroparine.The primary end point is to analyze during the in-hospital stay phase the stability of the anti Xa activity within the therapeutic ranges which will be estimated between 0.5 to 1.0 IU during the first 48 hours.

Capítulo de controversias en hemostasia y trombosis / Controversy chapter in haemostasia and thrombosis

Patients with gastrointestinal bleeding and high risk thromboembolitic disease (as in the first three months after a DVT or the first after an arterial embolism), should re-start anticoagulation with heparin, low dose, either iv or sc as soon as bleeding has stopped. Oral anticoagulants could be started a week after bleeding. There is not enough experience with LMWH (100 U anti Xa-Kg-day), but it´s more difficult to reverse while bleeding and renders it unsafe. Patients with acute Pulmonary embolism in their first month of treatmentshould be offered a inferior cava filter as a first option. Patients under anticoagulation with a moderate risk cardioembolic disease should switch to aspirin 325 mg per day plus gastroprotection, until the bleeding risk had disappeared. There is no need to confirm thet the bleeding disease (such as peptic ulcer) is cured before recommence anticoagulation. We suggest some general recomendations such as no alcohol or antiinflamatory drugs, treatment of Helycobacter Pilory, to target the INR at a lower level, and perhaps, to check anticoagulation more frequently. In a CNS bleeding in high risk thromboembolic patients, if there is an associated bleeding factor such as hipertention, trauma, INR higher than 5 or a stroke with haemorragic transformation, recommence anticoagulation after 7-14 days with iv heparin, and then oral anticoagulants at least 2 weeks after the bleeding episode. If the CNS bleeding is spontaneous, or associated with a tumor, a vascular malformation, or amyloidosis, then recommence anticoagulation only in very high risk patients and after 14-21 days of the acute episode. Moderate risk patients should wait at least a month until reiniciate anticoagulation. Finally, always reiniciate anticoagulation with the consent of the neurologist (AU)

Capítulo de controversias en hemostasia y trombosis / Controversy chapter in haemostasia and thrombosis

Patients with gastrointestinal bleeding and high risk thromboembolitic disease (as in the first three months after a DVT or the first after an arterial embolism), should re-start anticoagulation with heparin, low dose, either iv or sc as soon as bleeding has stopped. Oral anticoagulants could be started a week after bleeding. There is not enough experience with LMWH (100 U anti Xa-Kg-day), but itïs more difficult to reverse while bleeding and renders it unsafe. Patients with acute Pulmonary embolism in their first month of treatmentshould be offered a inferior cava filter as a first option. Patients under anticoagulation with a moderate risk cardioembolic disease should switch to aspirin 325 mg per day plus gastroprotection, until the bleeding risk had disappeared. There is no need to confirm thet the bleeding disease (such as peptic ulcer) is cured before recommence anticoagulation. We suggest some general recomendations such as no alcohol or antiinflamatory drugs, treatment of Helycobacter Pilory, to target the INR at a lower level, and perhaps, to check anticoagulation more frequently. In a CNS bleeding in high risk thromboembolic patients, if there is an associated bleeding factor such as hipertention, trauma, INR higher than 5 or a stroke with haemorragic transformation, recommence anticoagulation after 7-14 days with iv heparin, and then oral anticoagulants at least 2 weeks after the bleeding episode. If the CNS bleeding is spontaneous, or associated with a tumor, a vascular malformation, or amyloidosis, then recommence anticoagulation only in very high risk patients and after 14-21 days of the acute episode. Moderate risk patients should wait at least a month until reiniciate anticoagulation. Finally, always reiniciate anticoagulation with the consent of the neurologist

Capítulo de controversias en hemostasia y trombosis / Haemostasia and thrombosis. A controversial chapter

When should we consider to stop anticoagulation (AO) in venous Thromboembolism? a)In a patient with resolved risk factor like surgery and proximal deep vein thrombosis (DVT): between 6 weeks and 3 months. In a patient with distal DVT 6 weeks of anticoagulation is enough. b)A patient with unknow risk factor (spontanous DVT) with thrombophilic study negative: at least 6 month of AO. It may be better one year? c)A patient with low risk thrombophilia, first event, for example: Factor V Leiden heterocigote, hyperhomocysttenemia, Prothombin 2021 A, abnormal fibrinolytic system, at least 6 month of AO. d)In a patient with high risk Thrombophilia, first event, as Protein S,C or Antithrombin deficiency, antiphospholipid antibodies, or two low risk thrombophilic factors combined: 6 month to one year of AO and if the risk factor do not resolve treatment should be continued indefinitely. e)Patients with ongoing risk factorslike second idiopathic DVT, an active malignancy, a pulmonary embolism with pulmonary chronic hypertention or a DVT with inferrior vena cava interruption without contraindication to Ao should continue with AO indefinitely (AU)

Capítulo de controversias en hemostasia y trombosis / Haemostasia and thrombosis. A controversial chapter

When should we consider to stop anticoagulation (AO) in venous Thromboembolism? a)In a patient with resolved risk factor like surgery and proximal deep vein thrombosis (DVT): between 6 weeks and 3 months. In a patient with distal DVT 6 weeks of anticoagulation is enough. b)A patient with unknow risk factor (spontanous DVT) with thrombophilic study negative: at least 6 month of AO. It may be better one year? c)A patient with low risk thrombophilia, first event, for example: Factor V Leiden heterocigote, hyperhomocysttenemia, Prothombin 2021 A, abnormal fibrinolytic system, at least 6 month of AO. d)In a patient with high risk Thrombophilia, first event, as Protein S,C or Antithrombin deficiency, antiphospholipid antibodies, or two low risk thrombophilic factors combined: 6 month to one year of AO and if the risk factor do not resolve treatment should be continued indefinitely. e)Patients with ongoing risk factorslike second idiopathic DVT, an active malignancy, a pulmonary embolism with pulmonary chronic hypertention or a DVT with inferrior vena cava interruption without contraindication to Ao should continue with AO indefinitely

PAICA: método de detcción de autoanticuerpos plaquetarios en pacientes con púrpura trombocitopénica inmunológica / PAICA: Test for autoantibodies platelet in patients with idiopathic thrombocytopenic purpura

La PTI (Púrpura Trombocitopénica Inmunológica) se caracteriza por destrucción de las plaquetas al depositarse sobre sus membranas autoanticuerpos o complejos inmunes. El sitio de destrucción es usualmente el sistema reticuloendotelial del bazo y menos frecuentemente el del hígado. Su diagnóstico requiere estudios que demuestren la presencia de estos anticuerpos. Nuestro objetivo es evaluar la eficacia de un método para detectar autoanticuerpos unidos a glicoproteínas específicas (GP) de la membrana plaquetaria (PAICA: Platelet-Associated IgG Characterization Assay), y su correlación con los resultados obtenidos por PAIgG Platelet-Associated IgG). para ello se estudiaron 37 pacientes (28 mujeres y 9 varones) caracterizados como PTI por presentar trombactopenia y megacariocitos normales o aumentados en médula ósea. Se investigó la presencia de IgG asociada a plaquetas por el método PAIgG (Leporrier M. et al, 1979) que detecta el total de inmunoglobulina unida a la membrana de la plaqueta intacta y por PAICA (Laurent Macchi et al, 1996), que permite identificar la gliocoproteína target por medio del uso de anticuerpos monoclonales dirigidos contra GPIIbIIa y IbIX, sobre un listado plaquetario. Trece pacientes fueron negativos por ambos métodos; 20 tuvieron PAICA positivo y 15 de ellos también PAIgG positivo. Otros 4 pacientes mostroron positividad por PAIgG y no por PAICA. La especificidad encontrada por PAICA fue: 8 contra GPIIbIIIa, 8 contra IbIX, y 4 contra ambas GP. En conclusión, el método PAICA demuestra buena sensibilidad para la detección de anticuerpos antiplaquetas y permite confirmar la etiología autoinmune, lo que significa una ventaja importante en el diagnóstico de PTI (AU)

PAICA: método de detcción de autoanticuerpos plaquetarios en pacientes con púrpura trombocitopénica inmunológica / PAICA: Test for autoantibodies platelet in patients with idiopathic thrombocytopenic purpura

La PTI (Púrpura Trombocitopénica Inmunológica) se caracteriza por destrucción de las plaquetas al depositarse sobre sus membranas autoanticuerpos o complejos inmunes. El sitio de destrucción es usualmente el sistema reticuloendotelial del bazo y menos frecuentemente el del hígado. Su diagnóstico requiere estudios que demuestren la presencia de estos anticuerpos. Nuestro objetivo es evaluar la eficacia de un método para detectar autoanticuerpos unidos a glicoproteínas específicas (GP) de la membrana plaquetaria (PAICA: Platelet-Associated IgG Characterization Assay), y su correlación con los resultados obtenidos por PAIgG Platelet-Associated IgG). para ello se estudiaron 37 pacientes (28 mujeres y 9 varones) caracterizados como PTI por presentar trombactopenia y megacariocitos normales o aumentados en médula ósea. Se investigó la presencia de IgG asociada a plaquetas por el método PAIgG (Leporrier M. et al, 1979) que detecta el total de inmunoglobulina unida a la membrana de la plaqueta intacta y por PAICA (Laurent Macchi et al, 1996), que permite identificar la gliocoproteína target por medio del uso de anticuerpos monoclonales dirigidos contra GPIIbIIa y IbIX, sobre un listado plaquetario. Trece pacientes fueron negativos por ambos métodos; 20 tuvieron PAICA positivo y 15 de ellos también PAIgG positivo. Otros 4 pacientes mostroron positividad por PAIgG y no por PAICA. La especificidad encontrada por PAICA fue: 8 contra GPIIbIIIa, 8 contra IbIX, y 4 contra ambas GP. En conclusión, el método PAICA demuestra buena sensibilidad para la detección de anticuerpos antiplaquetas y permite confirmar la etiología autoinmune, lo que significa una ventaja importante en el diagnóstico de PTI

Epidemiología de los estados trombofílicos / Epidemiology of the thrombophilic states

Esta revisión hace referencia a la epidemiología de los estados trombofílicos más importantes, con todas las dificultades para establecer su verdadera prevalencia, la cual se halla influenciada por diversos factores: demográficos, diagnósticos, poblacionales, entre otros. De los pacientes con antecedentes trombóticos recurrentes y/o historia familiar, sólo un 10 por ciento obedece a una trombofilia, existiendo alrededor de un 25 por ciento que posiblemente la presente, pero en donde su etiología no ha podido ser determinada con los métodos hoy disponibles. Las alteraciones fibrinolíticas continúan siendo objeto de discusión, con respecto a la relevancia clínica y a su carácter hereditario