Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico / Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients

Introducción: Los hematomas son una causa poco frecuente deobstrucción intestinal. La heparina subcutánea tiene riesgo de producirla punción directa de un asa intestinal, provocando un hematoma trau-mático que genere una obstrucción intestinal. Casos clínicos: Se describen tres casos de pacientes pediátricos conclínica de obstrucción intestinal en tratamiento con heparina subcutánea.Dos casos presentaron elevación de reactantes de fase aguda y signosradiológicos de sufrimiento intestinal por lo que se optó por tratamientoquirúrgico, con el hallazgo intraoperatorio de hematoma intramural. Eltercer caso fue manejado de manera conservadora con supresión de laanticoagulación y reposo intestinal, dado el adecuado estado generaly ausencia de hallazgos compatibles con isquemia o necrosis en laspruebas complementarias. Comentarios: La administración de heparina subcutánea puedeprovocar la aparición de hematomas de pared intestinal, tanto por suefecto anticoagulante, como por el riesgo de punción inadvertida deun asa intestinal.(AU)

Introduction: Hematomas are a rare cause of intestinal obstruc-tion. Subcutaneous heparin can bring about direct punctures on smallbowel loops, potentially leading to traumatic hematoma and intestinalobstruction. Case reports: We present three cases of pediatric patients withclinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signsof intestinal suffering, so surgical treatment was decided upon, withintramural hematoma emerging as an intraoperative finding. The thirdcase was conservatively managed with anticoagulant discontinuationand gut rest, since the patient had an adequate general condition andno findings compatible with ischemia or necrosis were noted in thecomplementary tests. Discussion: The administration of subcutaneous heparin may causeintestinal wall hematomas due to its anticoagulating effect and to therisk of inadvertent punctures on small bowel loops.(AU)

[Translated article] Risk of venous thromboembolism in thromboprophylaxis between aspirin and low molecular weight heparins after total hip arthroplasty or total knee arthroplasty: Systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the efficacy of aspirin versus low molecular weight heparins (LMWH) for the prophylaxis of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing total knee arthroplasty (TKA) and/or total hip arthroplasty (THA). MATERIALS AND METHODS: Systematic review and meta-analysis. Sixteen studies were selected. The risk of VTE, DVT and PE were analysed. Mortality, risk of bleeding and surgical wound complications was also analysed. RESULTS: 248,461 patients were included. 176,406 patients with thromboprophylaxis with LMWH and 72,055 patients with aspirin thromboprophylaxis. There were no significant differences in the risk of VTE (OR=0.93; 95% CI: 0.69-1.26; p=0.64), DVT (OR=0.72; 95% CI: 0.43-1.20; p=0.21) or PE (OR=1.13; 95% CI: 0.86-1.49; p=0.38) between both groups. No significant differences were found in mortality (p=0.30), bleeding (p=0.22), or complications in the surgical wound (p=0.85) between both groups. These same findings were found in the sub-analysis of only randomised clinical trials (p>0.05). CONCLUSIONS: No increased risk of PE, DVT, or VTE was found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis. There was also no greater mortality, greater bleeding, or greater complications in the surgical wound found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis.

Tromboprofilaxis en COVID-19. Nuevas evidencias / COVID-19 thromboprophylaxis: New evidences

Recientes publicaciones han puesto en duda la eficacia de la utilización de dosis terapéuticas o intermedias de heparina de bajo peso molecular (HBPM) en pacientes COVID-19, especialmente en los pacientes más graves. Con el objetivo de actualizar estas recomendaciones se ha realizado una revisión no sistemática en las principales bases de datos médicas. Se seleccionaron un total de 14 ensayos clínicos aleatorizados, 14 metaanálisis y las recomendaciones de 12 sociedades científicas, estratificadas según el tipo de paciente (ambulatorio, hospitalizado, ingresado en cuidados críticos o post-alta). Se ha analizado la eficacia de HBPM y también de otras aproximaciones terapéuticas (rivaroxabán, apixabán, sulodexida, ácido acetilsalicílico e inhibidores P2Y12). Los hallazgos recomiendan utilizar dosis estándar de HBPM como tromboprofilaxis en los pacientes COVID-19 hospitalizados críticos y dosis terapéutica en hospitalizados no críticos si el riesgo de sangrado es bajo. En los pacientes ambulatorios y dados de alta del hospital podría utilizarse HBPM a dosis profiláctica si existen factores de riesgo trombótico y el riesgo hemorrágico es bajo. No se recomienda asociar antiagregantes plaquetarios a la HBPM salvo indicación previa.(AU)

Recent publications have questioned the efficacy of using therapeutic or intermediate doses of low molecular weight heparin (LMWH) in COVID-19 patients, especially in the most severe patients. In order to update these recommendations, a non-systematic review has been carried out in the main medical databases. A total of 14 randomized clinical trials, 14 meta-analyses and the recommendations of 12 scientific societies were selected, stratified according to the type of patient (outpatient, hospitalized, admitted to critical care or post-discharge). The efficacy of LMWH and other therapeutic approaches (rivaroxaban, apixaban, sulodexide, acetylsalicylic acid and P2Y12 inhibitors) has been analyzed. The findings recommend using standard doses of LMWH as thromboprophylaxis in critically hospitalized COVID-19 patients and therapeutic doses in non-critically hospitalized patients with low bleeding risk. In outpatients and those discharged from the hospital, LMWH could be used at a prophylactic dose if there are thrombotic risk factors, and the bleeding risk is low. It is not recommended to associate antiplatelet agents with LMWH unless previously indicated.(AU)

COVID-19 thromboprophylaxis. New evidence.

Recent publications have questioned the efficacy of using therapeutic or intermediate doses of low molecular weight heparin (LMWH) in COVID-19 patients, especially in the most severe patients. In order to update these recommendations, a non-systematic review has been carried out in the main medical databases. A total of 14 randomized clinical trials, 14 meta-analyses and the recommendations of 12 scientific societies were selected, stratified according to the type of patient (outpatient, hospitalized, admitted to critical care or post-discharge). The efficacy of LMWH and other therapeutic approaches (rivaroxaban, apixaban, sulodexide, acetylsalicylic acid and P2Y12 inhibitors) has been analyzed. The findings recommend using standard doses of LMWH as thromboprophylaxis in critically hospitalized COVID-19 patients and therapeutic doses in non-critically hospitalized patients if the risk of bleeding is low. In outpatients and those discharged from the hospital, LMWH could be used at a prophylactic dose if there are thrombotic risk factors, and the bleeding risk is low. It is not recommended to associate antiplatelet agents with LMWH unless previously indicated.

Efecto de la técnica de la tos durante la inyección subcutánea de heparina sobre la severidad del dolor y la satisfacción individual / Effect of the coughing technique during subcutaneous heparin injection on pain severity and individual satisfaction / Efeito da técnica de tosse durante injeção subcutânea de heparina na intensidade da dor e satisfação individual

Objetivo: examinar el efecto de la técnica de tos de mediana intensidad durante la inyección subcutánea de heparina de bajo peso molecular sobre la severidad del dolor y la satisfacción individual en pacientes de cirugía general. Método: estudio prospectivo, cuasi experimental, que incluyó a 100 pacientes a los que se les prescribió una inyección subcutánea de heparina de bajo peso molecular una vez cada 24 horas. Cada paciente recibió dos inyecciones por el mismo investigador utilizando técnica de inyección estándar con técnica de tos de intensidad media y solo técnica de inyección estándar. Resultados: hubo una diferencia estadísticamente significativa entre las puntuaciones medias de los pacientes sobre la intensidad del dolor y los niveles de satisfacción después de las inyecciones administradas por las dos técnicas (p= 0,000). Además, se encontró que el género afectó la severidad del dolor relacionado con la inyección, pero no afectó el nivel de satisfacción individual. Conclusión: se encontró que la técnica de tos de intensidad media reduce la severidad del dolor y aumenta la satisfacción del paciente de cirugía general que reciben inyecciones subcutáneas de heparina de bajo peso molecular. Registro del ensayo: NCT05681338.

Objective: to examine the effect of the medium intensity coughing technique during subcutaneous low molecular weight heparin injection on pain severity and individual satisfaction in general surgery patients. Method: the prospective, quasi-experimental study included 100 patients who had been prescribed a subcutaneous low molecular weight heparin injection once in 24 hours. Each patient received two injections by the same researcher, one using the standard injection technique with medium intensity coughing technique and the other only the standard injection technique. Results: there was a statistically significant difference between patients' mean scores on pain severity and satisfaction levels after injections administered by the two techniques (p= 0.000). Also, it was found that gender affected pain severity relating to the injection but did not affect the level of individual satisfaction. Conclusion: the medium intensity coughing technique was found to reduce pain severity and increase patient satisfaction in general surgery patients receiving subcutaneous low molecular weight heparin injections. Trial registration: NCT05681338.

Objetivo: examinar o efeito da técnica de tosse de média intensidade durante injeção subcutânea de heparina de baixo peso molecular na intensidade da dor e satisfação individual em pacientes submetidos à cirurgia geral. Método: estudo prospetivo, quasi experimental que incluiu 100 pacientes que haviam recebido uma injeção subcutânea de heparina de baixo peso molecular em 24 horas. Cada paciente recebeu duas injeções pelo mesmo pesquisador usando a técnica de injeção padrão com técnica de tosse de média intensidade e apenas técnica de injeção padrão. Resultados: houve diferença estatisticamente significativa entre as pontuações médias dos pacientes quanto à gravidade da dor e níveis de satisfação após as injeções administradas pelas duas técnicas (p = 0,000). Além disso, verificou-se que o sexo do paciente afetou a intensidade da dor relacionada à injeção, mas não afetou o nível de satisfação individual. Conclusão: a técnica de tosse de média intensidade reduz a intensidade da dor e aumenta a satisfação de pacientes submetidos à cirurgia geral recebendo injeções subcutâneas de heparina de baixo peso molecular. Registro do ensaio clínico: NCT05681338.

Sellado antibiótico de reservorios subcutáneos: estabilidad de soluciones con vancomicina / Antimicrobial lock solutions for implantable central venous devices: stability of vancomycin solutions

Los reservorios subcutáneos son un tipo de catéter venoso central (CVC). Cuando se usan catéteres venosos centrales (CVC), el personal sanitario necesita evitar dos grandes riesgos: formación de coágulos e infecciones bacterianas. Para prevenir y evitar la contaminación de los catéteres en los pacientes hospitalizados y ambulatorios, se han implementado diversas alternativas, como el llamado “sellado antibiótico de catéteres” (SAC). De este modo, se ha sugerido la utilización de soluciones con agentes antimicrobianos, a las que se suelen adicionar sustancias con efecto anticoagulante y/o con efecto antibiofilm. Empero, se requiere que la estabilidad de dichas soluciones sea comprobada mediante técnicas como la cromatografía líquida de alta resolución (HPLC), además de las pruebas de eficacia antimicrobiana, para así poder establecer la seguridad de los pacientes. En este entorno, se plantea el presente trabajo de revisión bibliográfica, con el objetivo de incluir las investigaciones de mayor representación clínica a este respecto, para evidenciar el comportamiento de las soluciones de sellado antibiótico de catéteres en distintas condiciones de almacenamiento y uso. En particular, esta revisión se centra en soluciones con vancomicina. De acuerdo con los estudios consultados, las soluciones de vancomicina con citrato de sodio (agente quelante) son las que presentan las mejores características en cuanto a estabilidad físico-química y eficacia como soluciones de sellado.(AU)

Subcutaneous reservoirs are a type of central venous catheter. When using central venous catheters, healthcare workers need to avoid two major risks: clot formation and bacterial infections. To prevent and avoid catheter contamination in both hospitalized patients and outpatients, several strategies have been carried out, such as the so-called ” antibiotic-based catheter lock solution”. Therefore, it has been suggested to implement the use of solutions with antimicrobial agents, to which anticoagulant and/or antibiofilm substances are often added.However, the stability of such solutions needs to be tested by techniques such as high performance liquid chromatography (HPLC), in addition to antimicrobial efficacy testing, in order to establish patient safety. In consequence, this literature review aims to include the most clinically representative research towards these aspects, to demonstrate the behaviour of antibiotic-based catheter lock solutions under different conditions of storage and use. In particular, this review focuses on solutions containing vancomycin. According to the studies consulted, vancomycin solutions with sodium citrate (chelating agent) present the best stability characteristics in terms of physicochemical properties and efficacy.(AU)

Risk of venous thromboembolism in thromboprophylaxis between aspirin and low molecular weight heparins after total hip arthroplasty or total knee arthroplasty: Systematic review and meta-analysis. / Riesgo de tromboembolismo venoso en la tromboprofilaxis entre aspirina y heparinas de bajo peso molecular tras una artroplastia total de cadera o artroplastia total de rodilla. Revisión sistemática y metaanálisis.

INTRODUCTION: The aim of this study was to evaluate the efficacy of aspirin versus low molecular weight heparins (LMWH) for the prophylaxis of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing total knee arthroplasty (TKA) and/or total hip arthroplasty (THA). MATERIALS AND METHODS: Systematic review and meta-analysis. Sixteen studies were selected. The risk of VTE, DVT and PE were analyzed. Mortality, risk of bleeding and surgical wound complications was also analyzed. RESULTS: 248,461 patients were included. 176,406 patients with thromboprophylaxis with LMWH and 72,055 patients with aspirin thromboprophylaxis. There were no significant differences in the risk of VTE (OR = 0.93; 95% CI: 0.69-1.26; P = .64), DVT (OR = 0.72; 95% CI: 0.43-1.20; P = .21) or PE (OR = 1.13; 95% CI: 0.86-1.49; P = .38) between both groups. No significant differences were found in mortality (P = .30), bleeding (P = .22), or complications in the surgical wound (P = .85) between both groups. These same findings were found in the sub-analysis of only randomized clinical trials (P>.05). CONCLUSIONS: No increased risk of PE, DVT, or VTE was found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis. There was also no greater mortality, greater bleeding, or greater complications in the surgical wound found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis.

INTERFERENCIA DE HEPARINA EN LA DETERMINACIÓN DE PROTEÍNAS TOTALES POR EL MÉTODO DE BRADFORD / Heparin interference in the Bradford protein quantification assay

La determinación de proteínas totales es una técnica de rutina utilizada en la industria biofarmacéutica durante los procesos de purificación de derivados plasmáticos y/o producción de proteínas recombinantes; y la elección del método analítico es un paso crítico para la obtención de resultados confiables. En este trabajo se demostró la interferencia de heparina (Hep), un compuesto comúnmente utilizado como excipiente en la formulación de Concentrados de Factores de la Coagulación (CFC), en la determinación de proteínas por el método de Bradford, cuya interferencia no está descripta como tal en los insertos de los kits comerciales de Bradford ni en la Farmacopea Europea. Esta interferencia fue demostrada tanto en soluciones de Albúmina Sérica Bovina (BSA) fortificadas con Hep, como en muestras de CFC. Para una solución de BSA 40 mg %, la concentración límite de Hep que no interfiere en la determinación de proteínas totales fue de 1,6 UI/ml. Cabe destacar que, si se trabaja a un nivel menor de concentración de proteínas, una proteína diferente o mezclas complejas de proteínas, se debe evaluar el grado de interferencia para cada caso particular, pudiéndose utilizar los valores obtenidos en este trabajo como referencia. Alternativamente, se evaluó la neutralización de la Hep con Polybrene (Poly), previo a la determinación de proteínas por Bradford. En el caso de soluciones de BSA, el efecto interferente se revirtió logrando una correcta cuantificación de proteínas, mientras que en las muestras de CFC, la neutralización con Poly no fue efectiva. Por lo tanto, para considerar el uso de Poly, previo a la aplicación del método de Bradford, debe evaluarse cada caso particular según las características de la muestra proteica en estudio. Si esto no es posible, se recomienda la utilización de un método alternativo, por ejemplo, el colorimétrico que utiliza ácido bicinconínico.

Protein quantification in biological samples is a routine assay used in the biopharmaceutical industry during the purification procedures of plasma-derived products and/or recombinant proteins. Thus, choosing the method for this purpose is a critical step to obtaining reliable results. In this work, it was shown that Heparin (Hep), a compound commonly used as an excipient in the formulation step of Coagulation Factor Concentrates (CFC), interferes in protein quantification by the Bradford assay. This interference was proved both in solutions of Hep-fortified Bovine Serum Albumin (BSA) and in CFC samples. For a 40 mg % BSA solution, the Hep concentration which shows no interference in protein quantification is 1.6 IU/ml. It should be noted that a specific analysis must be carried out if working at a lower protein concentration, with a different protein, or with complex protein solutions, so the values obtained in this work can be used as a reference. Alternatively, Hep neutralization with Polybrene (Poly) was evaluated before protein determination by Bradford. In the case of BSA solutions, the interference was reversed and correct protein quantification was achieved, whereas in the CFC samples, the results were unsatisfactory. Until now, Hep interference in the Bradford assay has not been described in the scientific literature, nor listed in the inserts of the commercial kits for protein quantification by this method. It was concluded that for protein samples containing Hep, the choice of an alternative method, such as the one that uses bicinchoninic acid, is the most convenient option to obtain reliable results

Eficacia de la tromboprofilaxis con heparina de bajo peso molecular en pacientes críticos con COVID-19: estudio observacional, prospectivo y multicéntrico / Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study

Introducción: Los pacientes COVID-19 presentan una coagulopatía caracterizada por una elevada incidencia de complicaciones tromboembólicas. Ante la controversia existente sobre el manejo de la tromboprofilaxis, se llevó a cabo un estudio con el objetivo de analizar el efecto de las diferentes dosis de heparina de bajo peso molecular (HBPM) utilizadas en los pacientes críticos con COVID-19. Material y métodos: Se evaluaron datos del Reg-COVID-19. Se compararon 2 grupos de pacientes según la dosis de HBPM administrada: profilaxis y tratamiento. El objetivo primario fue determinar si había relación de la dosis de HBPM con la mortalidad. Los objetivos secundarios incluyeron la incidencia de eventos trombóticos y hemorrágicos, la duración de la estancia en la UCI, la ventilación mecánica invasiva y los parámetros trombóticos e inflamatorios. Resultados: Se analizaron datos de 720 pacientes, 258 en el grupo de profilaxis y 462 en el de tratamiento. La proteína C reactiva, la ventilación mecánica invasiva y el tratamiento con tocilizumab o corticosteroides se relacionaron con la elección de la dosis de HBPM. La incidencia de complicaciones hemorrágicas (66/720, 9,2%) y trombóticas (69/720, 9,6%) fue similar en ambos grupos, al igual que el curso temporal de los eventos trombóticos, que ocurrieron antes que los hemorrágicos (9 [3-18] y 12 [6-19] días, respectivamente). La mortalidad fue menor en el grupo de profilaxis (25,2 frente al 35,1%), pero al aplicar un modelo de ponderación de probabilidad inversa, no se encontraron diferencias entre los grupos. Conclusión: No se encontraron efectos beneficiosos ni perjudiciales relacionados con la administración de dosis profilácticas o terapéuticas de HBPM en pacientes críticos COVID-19, con una tasa similar de complicaciones hemorrágicas o trombóticas. A partir de estos resultados, consideramos que son necesarios más estudios para determinar el protocolo óptimo de tromboprofilaxis en estos pacientes.(AU)

Introduction: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. Metohds: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. Results: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (P=.819 and P=.265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. Conclusion: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.(AU)

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis / Eficacia y seguridad de los anticoagulantes orales directos para el tratamiento de la tromboembolia venosa asociada al cáncer: una revisión sistemática y un metaanálisis en red bayesiana

Introduction: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH).Materials and methodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses.ResultsSeven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk.ConclusionsCompared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events. (AU)

Introducción: Los anticoagulantes orales directos (ACOD) son eficaces en la prevención de la tromboembolia venosa (TEV) relacionada con el cáncer, cuya tasa de incidencia se estima en 4-20%. Sin embargo, la eficacia y seguridad de ACOD y heparina de bajo peso molecular (HBPM) siguen siendo controvertidas.Materiales y métodosDesde el inicio hasta el 15 de marzo de 2022 se realizaron búsquedas sistemáticas en las bases de datos de ensayos controlados aleatorios (ECA) en PubMed, The Cochrane Library, Embase, ClinicalTrials.gov. Se utilizó el modelo de efectos aleatorios para informar la razón de probabilidades (RP) y los intervalos de confianza (IC) de 95% para los metaanálisis directos y de red.ResultadosSe incluyeron siete estudios con un total de 3.242 pacientes. En comparación con HBPM, los ACOD tienen una tasa más baja de recurrencia de TEV (OR 0,62, IC 95%: 0,47 a 0,82, I2 = 0,0%). La frecuencia de hemorragias mayores fue similar (OR 1,30, IC 95% 0,77 a 2,18, I2 = 34,9%). Se observó un mayor riesgo de eventos en los ACOD. Cuando se evaluaron las hemorragias no mayores clínicamente relevantes (CRNMB) (OR 1,61, IC 95%: 1,17 a 2,22, I2 = 20,7%) y las hemorragias clínicamente relevantes (OR 1,39, IC 95%: 1,11 a 1,74, I2 = 0,0%), En los análisis de subgrupos, las hemorragias mayores en las neoplasias malignas gastrointestinales y genitourinarias fueron más frecuentes con los ACOD. Apixabán ocupó el primer lugar en la prevención de TEV y la reducción de eventos hemorrágicos mayores. Edoxabán tuvo el mayor riesgo de hemorragias mayores. Las HBPM demostraron tener menor riesgo de hemorragias mayores clínicamente relevantes y hemorragias clínicamente relevantes. (AU)

Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.

INTRODUCTION: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. METHODS: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. RESULTS: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (p = .819 and p = .265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. CONCLUSION: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4-20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). MATERIALS AND METHODS: PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. RESULTS: Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47-0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77-2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17-2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11-1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. CONCLUSIONS: Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

Uso de heparina versus citrato em cateter de hemodiálise: uma revisão sistemática / Use of heparin versus citrate in hemodialysis catheter: a systematic review / Uso de heparina versus citrato en catéter de hemodiálisis: una revisión sistemática

A heparina é a solução mais utilizada para selar cateteres de hemodiálise. Entretanto, seu uso está associado a complicações locais e sistêmicas. A solução de citrato surge como alternativa devido aos seus efeitos anticoagulantes. O objetivo desta revisão sistemática é avaliar o risco de infecção da corrente sanguínea relacionada ao cateter usando heparina em comparação com solução de bloqueio de citrato. Esta revisão sistemática seguiu o protocolo Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a estratégia Population, Intervention, Comparison, Outcome (PICO), bem como utilizou as bases de dados Medline, Lilacs e Scielo. Buscaram-se ensaios clínicos randomizados que comparassem heparina com citrato como solução de bloqueio associada à infecção de corrente sanguínea relacionada a cateter. Inicialmente, foram encontrados 1.204 artigos. Após a leitura de seus títulos e resumos, foram selecionados 33 estudos. Depois da aplicação dos critérios de exclusão, restaram quatro artigos. Destes, o desfecho primário foi infecção da corrente sanguínea relacionada ao cateter. Em Weijmer et al. houve redução no grupo citrato. Por outro lado, Barcellos et al. mostraram resultados opostos usando o modelo multivariado. Power et al. não identificaram diferença entre os grupos e Winnett et al. favoreceram o grupo citrato usando análise de subgrupo. Não foi possível determinar diferença entre o grupo citrato e heparina na redução da infecção da corrente sanguínea relacionada ao cateter. São necessários mais estudos utilizando uma população maior e solução padronizada de citrato ou heparina.

As the most used solution to seal hemodialysis catheters, heparin use is associated with local and systemic complications. Citrate solution emerges as an alternative due to its anticoagulant effects. This systematic review sought to evaluate the risk of catheter-related bloodstream infection using heparin compared to citrate lock solution. Based on the PRISMA protocol and PICO strategy, data were collected from the Medline, Lilacs and Scielo databases. The search strategy included randomized clinical trials that compared heparin versus citrate as lock solution associated with catheter-related bloodstream infection. Of the 1,204 articles identified, 33 were selected after reading tittles and abstract. After applying the exclusion criteria, four papers were included for review. Primary outcome was catheter-related bloodstream infection. Weijmer et al. observed a reduction in the citrate group. In turn, Barcellos et al. showed opposite results using a multivariate model. Power et al. found no difference between groups and Winnet et al. favored the citrate group using subgroup analysis. Results on the difference between citrate versus heparin in reducing catheter-related bloodstream infection were inconclusive. Further studies using a bigger population and standardized citrate or heparin solution are needed.

La heparina es muy utilizada para sellar catéteres de hemodiálisis. Sin embargo, su uso se asocia a complicaciones locales y sistémicas. La solución de citrato puede ser una alternativa por sus efectos anticoagulantes. El objetivo de esta revisión sistemática es evaluar el riesgo de infección del torrente sanguíneo relacionada con el catéter en el uso de heparina en comparación con la solución bloqueadora de citrato. Esta revisión sistemática siguió el protocolo PRISMA y la estrategia PICO, así como las bases de datos Medline, Lilacs y SciELO, para buscar ensayos clínicos aleatorizados que habían comparado la heparina versus citrato como solución bloqueadora asociada a la infección del torrente sanguíneo relacionada con el catéter. Inicialmente se encontraron 1.204 artículos. Realizada la lectura de sus títulos y resúmenes, se seleccionaron 33 textos. Después de aplicar los criterios de exclusión, quedaron cuatro artículos. De estos, el resultado primario fue la infección del torrente sanguíneo relacionada con el catéter. En Weijmer et al. hubo una reducción en el grupo de citrato. Por otro lado, Barcellos et al. mostró resultados opuestos utilizando el modelo multivariado. Power et al. no mostraron diferencias entre los grupos, y Winnet et al. favorecieron al grupo citrato mediante análisis de subgrupos. No fue posible determinar una diferencia entre el grupo de citrato y el de heparina en la reducción de la infección del torrente sanguíneo relacionada con el catéter. Se necesitan más estudios que utilicen una población mayor y una solución estandarizada de citrato o heparina.

The addition of Tirofiban infusión to heparin for intraoperative heparin resistance associated with Marfan Syndrome / Adición de una infusión de Tirofiban a heparina en caso de resistencia intraoperatoria a la heparina asociada al Síndrome de Marfan

Abstract Marfan syndrome classically presents with aortic root aneurysms. Aortic ectasia causes diverse blood flow alterations, influencing the behavior of coagulation factors and platelet activity. Heparin resistance has also been reported associated with Marfan Syndrome in a small number of patients, probably due to antithrombin III (ATIII) deficiency or various mutations. The ascending aorta and the aortic valve are replaced with prosthetic material during Bentall- de Bonno procedures. Resistance to anticoagulation during extracorporeal circulation, represents a significant challenge for both anesthesiologists and the surgical team. Resistance to heparin was observed in a patient with Marfan syndrome undergoing a Bentall procedure. ATIII concentrate was not available, and Activated Coagulation Time did not increase despite high doses of heparin. An alternate anticoagulation approach was used successfully.

Resumen El síndrome de Marfan clásicamente se presenta con aneurismas de la raíz de la aorta. La ectasia aórtica produce alteraciones en el flujo sanguíneo que influyen sobre el comportamiento de los factores de la coagulación y la actividad de las plaquetas. También se ha reportado resistencia a la heparina asociada al Síndrome de Marfan en un menor número de pacientes, probablemente debido a deficiencia de antitrombina III (ATIII) o a diversas mutaciones. La aorta ascendente y la válvula aórtica se reemplazan con material prostético en los procedimientos Bentall- de Bonno. La resistencia a la anticoagulación durante circulación extracorpórea significa un enorme desafío tanto para los anestesiólogos, como para el equipo quirúrgico. Se observó resistencia a la heparina en un paciente con Síndrome de Marfan sometido a un procedimiento de Bentall. No había disponibilidad de concentrado ATIII y no aumentó el Tiempo de Coagulación Activada a pesar de las elevadas dosis de heparina. Se utilizó exitosamente un abordaje alterno de anticoagulación.

Tromboprofilaxis precoz y evolución en embarazadas con COVID-19 / Early thromboprophylaxis and evolution in pregnant women with COVID-19

Introducción: en marzo del año 2020 se declara Pandemia, por la aparición de un nuevo Coronavirus, el SARS-CoV2 (COVID-19). Las mujeres embarazadas presentan un riesgo mayor de presentar procesos tromboembólicos, por lo que se recomienda utilizar de manera profiláctica heparina, para prevención de procesos tromboembólicos durante la infección por SARS-CoV2. Objetivo: Describir la evolución de las embarazadas con infección por SARS-CoV2 con la utilización de heparina de bajo peso molecular, Enoxaparina, ajustada al peso de manera precoz. Metodología: estudio descriptivo prospectivo, observacional, de corte transversal. Resultados: en la evolución de 30 mujeres embarazadas con infección por SARS-CoV2, las edades más frecuentes corresponden a 31 a 35 años, mayor número de infectadas en el segundo trimestre del embarazo, el índice de masa corporal predominante en rango de sobrepeso y obesidad, la dosis de enoxaparina utilizada fue de 40 mg/día, ya que se ajustó al peso de la embarazada, las comorbilidades más frecuentes correspondieron al sobrepeso y obesidad, enfermedad hipertensiva del embarazo y diabetes gestacional, la sintomatología resultó muy variada, debido a las distintas variantes del virus, con más frecuencia la rinorrea, congestión nasal, tos, anosmia, disgeusia, cefalea, fiebre y dificultad respiratoria, y la mayoría de las embarazadas no estaban vacunadas. Conclusiones: ninguna de las 30 embarazadas que recibieron heparina de bajo peso molecular (Enoxapina), ajustada al peso, y de manera precoz, con infección por SARS.CoV2, falleció, ni requirió internación en Unidad de Terapia Intensiva. Una embarazada, fue internada por disnea moderada y saturación de oxígeno menor a 95%. Las restantes embarazadas tuvieron buena evolución en su domicilio, sin ninguna complicación

Introduction: in March 2020, a Pandemic was declared, due to the appearance of a new Coronavirus, SARS-CoV2 (COVID-19). Pregnant women have a higher risk of presenting thromboembolic processes, so it is recommended to use heparin prophylactically, to prevent thromboembolic processes during SARS-CoV2 infection. Objective: to describe the evolution of pregnant women with SARS-CoV2 infection with the early use of Enoxaparin, adjusted to the weight of low molecular weight heparin. Methodology: prospective, observational, cross-sectional descriptive study. Results: in the evolution of 30 pregnant women with SARS-CoV2 infection, the most frequent ages correspond to 31 to 35 years, the highest number of infected in the second trimester of pregnancy, the predominant body mass index in the range of overweight and obesity. , the dose of enoxaparin used was 40 mg/day, since it was adjusted to the weight of the pregnant woman, the most frequent comorbidities were overweight and obesity, hypertensive disease of pregnancy and gestational diabetes, the symptoms were highly varied, due to the different variants of the virus, more frequently rhinorrhea, nasal congestion, cough, anosmia, dysgeusia, headache, fever and respiratory distress, and most of the pregnant women were not vaccinated. Conclusions: none of the 30 pregnant women who received low molecular weight heparin (Enoxapine), adjusted for weight, and early, with SARS.CoV2 infection, died or required admission to the Intensive Care Unit. A pregnant woman was hospitalized due to moderate dyspnea and oxygen saturation less than 95%. The remaining pregnant women had a good evolution at home, without any complications

Actualización sobre trombofilias y gestación / Update on thrombophilia and pregnancy

El embarazo constituye un factor de riesgo independiente de eventos tromboembólicos, provocado por los cambios en la hemostasia que se producen durante la gestación. Las trombofilias son trastornos de la hemostasia que predisponen a eventos trombóticos. La creciente evidencia sugiere que las trombofilias se asocian a enfermedad tromboembólica y resultados obstétricos desfavorables. Sin embargo, las limitaciones metodológicas han dificultado la obtención de una visión general clara de los riesgos que suponen durante la gestación. El objetivo del presente artículo es realizar una revisión bibliográfica exhaustiva sobre el uso de tromboprofilaxis durante la gestación, con especial interés en esclarecer qué trombofilias tienen indicación de anticoagulación durante el embarazo basada en una mejora de los resultados obstétricos demostrados en la literatura científica.(AU)

Pregnancy is an independent risk factor for thromboembolic events, caused by changes in haemostasis that occur during pregnancy. Thrombophilia comprises disorders of haemostasis that predispose to thrombotic events. Increasing evidence suggests that thrombophilia is associated with thromboembolic disease and poor obstetric outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the risk they pose during pregnancy. The objective of this article is to carry out an exhaustive bibliographic review on the use of thromboprophylaxis during pregnancy, with special interest in clarifying the thrombophilia for which anticoagulation is indicated during pregnancy based on an improvement in obstetric results demonstrated in the scientific literature.(AU)

Trombosis venosa profunda masiva en gestante: la importancia de individualizar el plan de acción / Massive deep vein thrombosis in pregnant women: The importance of individualizing the action plan

El tromboembolismo venoso (TEV), incluida la trombosis venosa profunda (TVP) y la embolia pulmonar (TEP) es una afección potencialmente letal y a tener en cuenta en mujeres embarazadas, donde la situación es favorecida por los cambios fisiológicos característicos de la gestación, el parto y el puerperio. El manejo de esta patología en este tipo de pacientes está basado en la anticoagulación, con los beneficios e inconvenientes que ello implica. Presentamos el caso de una mujer embarazada con TVP masiva e intentamos arrojar luz sobre temas como son la vía de parto (vaginal vs. cesárea) o el manejo del tratamiento (heparina de bajo peso molecular [HBPM] vs. heparina no fraccionada [HNF]) de cara a obtener la situación más segura para la paciente.(AU)

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially lethal condition to be taken into account in pregnant women, where the situation is favored by the characteristic physiological changes of the pregnancy, childbirth and the puerperium. The management of this pathology in this type of patient is based on anticoagulation, with the benefits and drawbacks that this implies. We present the case of a pregnant woman with massive DVT and the issues are discussed, such as the method of delivery (vaginal vs. cesarean section) or the management of treatment (LMWH vs. UFH) in order to obtain the safest situation for the patient.(AU)

Preferences and Practices of Brazilian Orthopedists for Thromboprophylaxis Techniques in Total Knee Arthroplasty: Survey Among Members of the Brazilian Society of Knee Surgery (SBCJ) / Preferências e práticas de ortopedistas brasileiros por técnicas de tromboprofilaxia na artroplastia total do joelho: Levantamento entre membros da Sociedade Brasileira de Cirurgia do Joelho (SBCJ)

Abstract Objective The present study describes the preferences and current practices of a sample of knee surgeons in Brazil regarding thromboprophylaxis in total knee arthroplasty (TKA). Method In the present internet survey, surgeons from the Brazilian Knee Surgery Society (SBCJ, in the Portuguese acronym) voluntarily answered an anonymous questionnaire including time of personal surgical experience, perceptions about the best thromboprophylaxis options, and actual practices in their work environment. Results From December 2020 to January 2021, 243 participants answered the questionnaire. All, except for 3 (1.2%), reported using thromboprophylaxis, and most (76%) combined pharmacological and mechanical techniques. The most prescribed drug was enoxaparin (87%), which changed to rivaroxaban (65%) after discharge. The time of thromboprophylaxis initiation varied according to the length of training of the knee surgeon (p ≤ 0.03), and their preferences and practices differed according to the Brazilian region (p< 0.05) and the health system in which the surgeons work (public or private sector; p= 0.024). The option for mechanical thromboprophylaxis also depended on the training time of the surgeon. Conclusion Thromboprophylaxis preferences and practices in TKA are diverse across Brazilian regions and health systems (public or private sectors). Given the lack of a national clinical guideline, most orthopedists follow either their hospital guidelines or none. The mechanical prophylaxis method and the little use of aspirin are the points that most diverge from international guidelines and practices.

Resumo Objetivo Descrever as preferências e práticas atuais de uma amostra de cirurgiões de joelho do Brasil quanto à forma de tromboprofilaxia na artroplastia total do joelho (ATJ). Método presente pesquisa realizada pela internet, cirurgiões associados à Sociedade Brasileira de Cirurgia do Joelho (SBCJ) foram convidados a responder voluntariamente a um questionário anônimo incluindo o tempo de experiência cirúrgica pessoal, percepções sobre as melhores opções de tromboprofilaxia e as reais práticas no ambiente onde trabalham. Resultados Entre dezembro de 2020 e janeiro de 2021, 243 participantes responderam ao questionário completo. Exceto por 3 (1,2%) participantes, todos declararam praticar tromboprofilaxia, a maioria (76%) combinando as formas farmacológica e mecânica. A droga mais prescrita é a enoxaparina (87%), com modificação para rivaroxabana (65%) após a alta. O momento de início da tromboprofilaxia variou conforme o tempo de formação do cirurgião de joelho (p ≤ 0,03) e as preferências e práticas variaram conforme a região do país (p< 0,05) e o sistema de saúde no qual trabalham os cirurgiões (público ou privado; p= 0,024). A opção por tromboprofilaxia mecânica também dependeu do tempo de formação do cirurgião. Conclusão As preferências e práticas de tromboprofilaxia na ATJ são diversas nas regiões do Brasil e sistemas de saúde (público ou privado). Dada a inexistência de uma diretriz clínica nacional, a maior parte dos ortopedistas segue ou a diretriz de seu próprio hospital ou nenhuma. O método de profilaxia mecânica e a pouca utilização do ácido acetilsalicílico são os pontos que mais destoam das diretrizes e práticas internacionais.

Massive deep vein thrombosis in pregnant women: The importance of individualizing the action plan.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially lethal condition to be taken into account in pregnant women, where the situation is favored by the characteristic physiological changes of the pregnancy, childbirth and the puerperium. The management of this pathology in this type of patient is based on anticoagulation, with the benefits and drawbacks that this implies. We present the case of a pregnant woman with massive DVT and the issues are discussed, such as the method of delivery (vaginal vs. cesarean section) or the management of treatment (LMWH vs. UFH) in order to obtain the safest situation for the patient.

Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) en COT, cambiará en algo nuestra práctica clínica? / International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice?

Las aportaciones del Consenso Internacional sobre Tromboembolismo Venoso (ICM-VTE) modificarán nuestra práctica diaria, recogiendo la evidencia actual que no aparece en la mayoría de las guías de práctica clínica hasta la fecha. Muchos de nuestros procedimientos de cirugía ortopédica y traumatología no requieren de una profilaxis tromboembólica que solo se administra cuando existen factores de riesgos individuales o cirugías mayores (artroplastia total de miembros inferiores, cirugía de columna o fracturas que requieran inmovilización y limitación en la carga precoz). Dentro de las opciones de profilaxis debemos tener en cuenta la potencia del fármaco para prevenir el tromboembolismo venoso, pero también el efecto de hemorragia y sangrado que pueda producir. El uso de aspirina y medidas mecánicas se establece como la combinación más segura y eficaz en muchos de los casos.(AU)

The International Consensus Meeting on Venous Thromboembolism (ICM-VTE), will change our current practice as most recent evidence is included. This fact is not usual in most clinical practice guidelines to date. Many orthopedic and trauma procedures do not require thromboembolic prophylaxis, but it should be considered depending on individual risk factors or major surgeries (total hip or knee arthroplasty, spine surgery or fractures that require immobilization and weight bearing restriction). Within the prophylaxis options, we must notice the strengh of the drug preventing venous thromboembolism, but also the effect of hemorrhage and bleeding that it may produce. The use of aspirin and mechanical prophylaxis has been described as the safest and most effective combination in most cases.(AU)