[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.

Randomized clinical trial of aspirin as prophylaxis for thromboembolism in hip arthroplasty / Ensaio randomizado da aspirina na profilaxia do tromboembolismo em artroplastia do quadril

ABSTRACT Objective: This study aims to evaluate aspirin as a chemical prophylaxis (200 mg) in total hip arthroplasty. Methods: the study compared two groups and used ultrasonography (USG) to screen for low-deep venous thrombosis. Group 1 received 600 mg (control), and Group 2 received 200 mg of (intervention), associated with the use of elastic compression stockings and early walking Results: fourteen patients were allocated to Group A (200mg), and 16 to Group B (600mg); in group A (200mg), 3 cases with thrombus below the popliteal vein were detected at the first USG examination. All of them are in the left lower limb (21.4%). In group B (600 mg), 5 cases were identified after the first exam (31.2%). All cases were asymptomatic and followed the protocol with prophylaxis only with Aspirin. Conclusion: In the statistical data, there were no differences in the presence of thrombus between the 200- and 600 mg groups, which is credited to using low-dose aspirin in low doses (200mg). Hematimetric levels returned to baseline levels and suggested there was no chronic or acute bleeding related to the use of aspirin. The manuscript was prepared according to the CONSORT guideline 2010. Level of Evidence I; Longitudinal Randomized Comparative Clinical Study.

RESUMO Objetivo: Este estudo pretende avaliar a aspirina como profilaxia química (200 mg) na artroplastia total do quadril. Métodos: estudo comparando dois grupos com diferentes doses de aspirina e utilizando a ultrassonografia (USG) para rastreamento da trombose venosa profunda baixa. O grupo 1, 650 mg ao dia de aspirina (controle) e o grupo 2, 200 mg de aspirina ao dia na mesma posologia (intervenção) e associados ao uso de meias elásticas de compressão e deambulação precoce. Resultados: quatorze pacientes foram alocados no grupo A (200 mg) e 16 no grupo B (650 mg). No grupo A foram detectados 3 casos com trombos abaixo da veia poplítea ao USG sendo 21,4%. Já no grupo B, 5 casos foram identificados após o primeiro exame (31,2%). Todos assintomáticos e sem sinais de sangramento ativo ou queda da hematimetria no momento da detecção dos trombos. Conclusão: os dados sugerem não haver diferença na incidência de trombo em ambos os grupos, não sendo a profilaxia com a aspirina dose-dependente. Os níveis hematimétricos retornaram aos níveis iniciais o que sugere não ter havido sangramento crônico ou agudo relacionado ao uso. Nível de Evidência I; Estudo Clínico Randomizado Longitudinal Comparativo.

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.

The Role and Mechanism of Aspirin Combined with Rehabilitation Training in the Repair of Sciatic Nerve Injury and the Changes in the Schwannocytus (Schwann Cells) in Rats / Rol y Mecanismo de la Aspirina Combinados con Entrenamiento de Rehabilitación en la Reparación de la Lesión del Nervio Ciático y los Cambios en los Schwannocitos (Células de Schwann) en Ratas

SUMMARY: This study investigated the role and mechanism of aspirin combined with rehabilitation training in the nerve injury repair and Schwann cell changes in rats with sciatic nerve injury. Totally, 120 male healthy SD rats were randomly divided into sham, model, aspirin, and aspirin + rehabilitation groups, with 30 rats in each group. The sciatic nerve function index (SFI), photothermal pain tolerance threshold and inclined plane test results at 4, 6, and 8 weeks after operation were compared. The distance of sensory nerve regeneration and the expression of S100B protein in Schwann cells were analyzed. Compared with the sham group, the SFI of the model, aspirin, and aspirin+rehabilitation groups were significantly lower at 4, 6, and 8 weeks after operation. However, the aspirin and aspirin+rehabilitation groups had significantly higher SFI than the model group. The SFI at 6 and 8 weeks after operation was higher in the aspirin+rehabilitation group than that in the aspirin group (P<0.05). The photothermal pain tolerance threshold of the sham, aspirin, and aspirin+rehabilitation groups were significantly higher than those of the model group at 4, 6, and 8 weeks after operation (P<0.05). The inclination angles of the model, aspirin, and aspirin+rehabilitation groups were significantly lower than those of the sham group at 4, 6, and 8 weeks after operation, and the inclination angle of the aspirin+rehabilitation group was significantly higher than that of the model and aspirin groups (P<0.05). The sensory nerve regeneration distance in aspirin and aspirin+rehabilitation groups was higher than that in the sham and model groups (P<0.05). The expression of S100B protein in the aspirin and aspirin+rehabilitation groups was higher than that in the model group (P<0.05). Aspirin combined with rehabilitation training can promote the functional recovery of sciatic nerve injury, and the mechanism may be related to the increase of the expression of S100B protein in Schwann cells.

En este estudio se investigó el papel y el mecanismo que desempeña la aspirina combinada, con el entrenamiento de rehabilitación en la reparación de lesiones nerviosas y los cambios en los schwannocitos en ratas con lesiones en el nervio ciático. En total, 120 ratas SD macho sanas se dividieron aleatoriamente en cuatro grupos de 30 ratas en cada uno: simulación, modelo, aspirina y aspirina + rehabilitación. Se compararon el índice de función del nervio ciático (SFI), el umbral de tolerancia al dolor fototérmico y los resultados de la prueba del plano inclinado a las 4, 6 y 8 semanas después de la operación. Se analizó la distancia de regeneración del nervio sensorial y la expresión de la proteína S100B en los schwannocitos. En comparación con el grupo simulado, el SFI de los grupos modelo, aspirina y aspirina+rehabilitación fue significativamente menor a las 4, 6 y 8 semanas después de la operación. Sin embargo, los grupos de aspirina y aspirina + rehabilitación tuvieron un SFI significativamente más alto que el grupo modelo. El SFI a las 6 y 8 semanas después de la operación fue mayor en el grupo de aspirina + rehabilitación que en el grupo de aspirina (P<0,05). El umbral de tolerancia al dolor fototérmico de los grupos simulado, aspirina y aspirina+rehabilitación fue significativamente mayor que el del grupo modelo a las 4, 6 y 8 semanas después de la operación (P<0,05). Los ángulos de inclinación de los grupos modelo, aspirina y aspirina+rehabilitación fueron significativamente menores que los del grupo simulado a las 4, 6 y 8 semanas después de la operación, y el ángulo de inclinación del grupo aspirina+rehabilitación fue significativamente mayor que el de los grupos modelo y aspirina (P<0.05). La distancia de regeneración del nervio sensorial en los grupos de aspirina y aspirina+rehabilitación fue mayor que en los grupos simulado y modelo (P<0,05). La expresión de la proteína S100B en los grupos de aspirina y aspirina+rehabilitación fue mayor que en el grupo modelo (P<0,05). La aspirina combinada con el entrenamiento de rehabilitación puede promover la recuperación funcional de la lesión del nervio ciático, y el mecanismo puede estar relacionado con el aumento de la expresión de la proteína S100B en los schwannocitos.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

Infections, including zoonoses, constitute a threat to human health due to the spread of resistant pathogens. These diseases generate an inflammatory response controlled by a resolving mechanism involving specialized membrane lipid-derived molecules called lipoxins, resolvins, maresins, and protectins. The production of some of these molecules can be triggered by aspirin or statins. Thus, it is proposed that modulation of the host response could be a useful therapeutic strategy, contributing to the management of resistance to antiparasitic agents or preventing drift to chronic, host-damaging courses. Therefore, the present work presents the state of the art on the use of statins or aspirin for the experimental management of parasitic infections such as Chagas disease, leishmaniasis, toxoplasmosis or malaria. The methodology used was a narrative review covering original articles from the last seven years, 38 of which met the inclusion criteria. Based on the publications consulted, modulation of the resolution of inflammation using statins may be feasible as an adjuvant in the therapy of parasitic diseases. However, there was no strong experimental evidence on the use of aspirin; therefore, further studies are needed to evaluate its role inflammation resolution process in infectious diseases.

Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Impact of pharmacogenetics on aspirin resistance: a systematic review / Impacto da farmacogenética na resistência à aspirina: uma revisão sistemática

Abstract Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR). Objectives To realize a systematic literature review to determine the impact of genetic variants on AR. Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included. Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p< 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences. Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.

Resumo Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA). Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina. Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído. Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p< 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais. Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA.

Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery / Avaliação do efeito da aspirina em baixa dose na prevenção do parto prematuro em mulheres com história de parto prematuro espontâneo

Abstract Objective Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low-dose aspirin is used to prevent pre-eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low-dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. Methods The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). Results Forty-three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). Conclusion The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low-dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Resumo Objetivo Atualmente, os distúrbios vasculares uteroplacentários são considerados um dos principais mecanismos de parto prematuro espontâneo (PTD). A aspirina em baixa dose é usada para prevenir a pré-eclâmpsia, que tem um mecanismo semelhante; portanto, o presente estudo teve como objetivo investigar o efeito da aspirina em baixa dosagem na prevenção de PTD em mulheres com história de PTD espontâneo. Métodos O presente ensaio clínico piloto randomizado foi realizado em 54 gestantes do grupo aspirina (tomando 80 mg diários até a 36ª semana e tratamento clássico) e 53 pacientes do grupo controle (somente tratamento clássico). Resultados Quarenta e três pacientes (40%) apresentaram-se antes de 37 semanas devido a sintomas de PTL. O parto prematuro (< 37 semanas) ocorreu em 28 pacientes (26%) e não houve diferença significativa entre os grupos aspirina e controle (10 pacientes [19%] e 18 pacientes [34%], respectivamente; p = 0,069). O tempo de parto prematuro foi precoce (< 34 semanas) em 6 pacientes (21%) e sua causa foi trabalho de parto espontâneo em 23 pacientes (82%) que não foi significativamente diferente entre os dois grupos (p > 0,05). Das 40 pacientes com trabalho de parto espontâneo, 25 pacientes (63%) tiveram PTD, que foi significativamente menor no grupo aspirina do que no grupo controle (9 pacientes [45%] versus 16 pacientes [80%], respectivamente; p = 0,022). Conclusão Os achados do presente estudo demonstraram que, apesar da redução na incidência de DPT com o uso de aspirina em baixa dosagem, a taxa de redução não foi estatisticamente significativa. Por outro lado, em pacientes com trabalho de parto espontâneo propensas a PTD, a aspirina foi eficaz na redução da incidência de PTD.

Aspirin and poetry: Did João Cabral de Melo Neto suffer from acetylsalicylic acid-overuse headache? / Aspirina e poesia: João Cabral de Melo Neto sofria de cefaleia por uso excessivo de ácido acetilsalicílico?

Introduction: João Cabral de Melo Neto is considered one of the most important Brazilian poets of all time. He suffered from severe headaches for the longest part of his life, being diagnosed with migraine. He took a significant amount of acetylsalicylic acid pills every day for many years. Objective: The objective of this narrative review includes identifying how headache and its treatment influenced João Cabral de Melo Neto's poetry as well as analyzing the correlation between Melo Neto's migraine diagnosis and his documented overuse of aspirin and investigating the possibility of an acetylsalicylic acid-overuse headache diagnosis. Methods: The authors thoroughly read biographical books and interviews about the life of João Cabral de Melo Neto. They systematically documented all references to headaches and aspirin. Melo Neto's clinical case documented in his biography and interviews were juxtaposed with The International Classification of Headache Disorders (ICHD-3) diagnostic criteria for acetylsalicylic acid-overuse headache diagnosis. Results: The word "aspirin" appears 8 times in 6 of Melo Neto's poems. He compares it to the sun, attributing to it the capacity to refocus a "blurred body" (his state during a headache). The poet reported that took one aspirin pill every hour every day, for several years. Conclusions: Headache and the use of acetylsalicylic acid influenced João Cabral de Melo Neto's poetry and life. He presented a risk behavior for developing medication overuse headache, specifically its subform: acetylsalicylic acid-overuse headache.

Introdução: João Cabral de Melo Neto é considerado um dos mais importantes poetas brasileiros de todos os tempos. Ele sofreu fortes dores de cabeça durante a maior parte de sua vida, sendo diagnosticado com enxaqueca. Ele tomou uma quantidade significativa de comprimidos de ácido acetilsalicílico todos os dias durante muitos anos. Objetivo: O objetivo desta revisão narrativa inclui identificar como a cefaleia e o seu tratamento influenciaram a poesia de João Cabral de Melo Neto, bem como analisar a correlação entre o diagnóstico de enxaqueca de Melo Neto e o seu documentado uso excessivo de aspirina e investigar a possibilidade de um diagnóstico de cefaleia por uso excessivo de ácido acetilsalicílico. Métodos: Os autores fazem leitura minuciosa de livros biográficos e entrevistas sobre a vida de João Cabral de Melo Neto. Eles documentaram sistematicamente todas as referências a dores de cabeça e aspirina. O caso clínico de Melo Neto documentado em sua biografia e entrevistas foi justaposto aos critérios diagnósticos da Classificação Internacional de Cefaleias (ICHD-3) para diagnóstico de cefaleia por uso excessivo de ácido acetilsalicílico. Resultados: A palavra "aspirina" aparece 8 vezes em 6 poemas de Melo Neto. Ele o compara ao sol, atribuindo-lhe a capacidade de reorientar um "corpo turvo" (seu estado durante uma dor de cabeça). O poeta relatou que tomou um comprimido de aspirina a cada hora, todos os dias, durante vários anos. Conclusões: A dor de cabeça e o uso de ácido acetilsalicílico influenciaram a poesia e a vida de João Cabral de Melo Neto. Apresentou comportamento de risco para desenvolver cefaleia por uso excessivo de medicamentos, especificamente sua subforma: cefaléia por uso excessivo de ácido acetilsalicílico.

Indicación profiláctica de aspirina para prevención de preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo / Prophylactic use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies

Resumen OBJETIVO: Sintetizar la evidencia disponible de los últimos 10 años respecto de la indicación de la aspirina para prevenir la preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo. METODOLOGÍA: Revisión de cinco bases de datos [Pubmed/Medline, ProQuest, Lilacs, HINARI y Cochrane Central Register of Controlled Trials (CENTRAL)]. Se incluyeron ensayos clínicos aleatorizados, controlados, escritos en español o inglés publicados entre enero de 2010 y enero de 2020. Se emplearon los términos de vocabulario controlado DeCS y MeSH en las distintas interfases. En el caso de ProQuest se introdujeron, además, términos de vocabulario libre. Los detalles de la estrategia de búsqueda se visualizan en anexos. RESULTADOS: Se identificaron 410 estudios, de los que se seleccionaron 8 que reunieron los criterios de elegibilidad. En dos estudios se encontró un efecto reductor de la aspirina en la incidencia de preeclampsia en comparación con placebo; otros dos estudios encontraron el mismo efecto en la incidencia de preeclampsia con parto pretérmino. No se encontraron estudios con bajo riesgo de sesgo que hubieran reportado un efecto significativo de la aspirina en las complicaciones de preeclampsia, ni en preeclampsia con y sin criterios de severidad. CONCLUSIONES: La evidencia señala que la aspirina en bajas dosis, indicada antes de las 16 semanas de embarazo, reduce la incidencia de preeclampsia debido a su efecto reductor en el parto pretérmino. A pesar de lo encontrado, la información sigue siendo limitada; de ahí la necesidad de contar con una mayor cantidad de estudios con bajo riesgo de sesgo.

Abstract OBJECTIVE: To synthesize the available evidence of the last 10 years regarding the use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies. Methodology: Five electronic databases [Pubmed/Medline, ProQuest, Lilacs, HINARI, and Cochrane Central Register of Controlled Trials (CENTRAL)] were reviewed. Randomized controlled clinical trials in Spanish and English published between 01/01/2010 and 01/01/2020 were considered. The DeCS and MeSH controlled vocabulary terms were used in the different interfaces. In the case of ProQuest, free vocabulary terms were also introduced. The details of the search strategy are displayed in annexes. RESULTS: 410 studies were identified, of which 8 studies that met the eligibility criteria were selected. 2 studies found a reducing effect of aspirin on the incidence of preeclampsia compared to placebo and another 2 studies found the same effect on the incidence of preeclampsia with preterm delivery. No studies with low risk of bias were found that have reported a significant effect of aspirin on the complications of preeclampsia, nor on preeclampsia with and without criteria of severity. CONCLUSIONS: there is evidence indicating that low-dose aspirin before 16 weeks of gestation reduces the incidence of preeclampsia, this is due to the reducing impact it has on the incidence of preeclampsia with preterm delivery. Despite the results found, the information is still limited, and it is necessary to have a greater number of studies with low risk of bias.

Sangramiento posextracción dentaria y medidas para su control en pacientes tratados con antiagregantes plaquetarios / Bleeding after tooth extraction and measures for its control in patients treated with antiplatelet agents

Introducción: El desarrollo de las ciencias médicas trae consigo un incremento en la expectativa de vida, junto a la detección temprana de un gran número de enfermedades crónicas como las cerebrovasculares y cardiovasculares, que son tratadas rutinariamente con medicamentos antiagregantes plaquetarios. El conocimiento del manejo de estos pacientes ante los procedimientos quirúrgicos estomatológicos constituye un reto en la práctica diaria profesional. Objetivo: Determinar el nivel de sangramiento posextracción dentaria en pacientes con enfermedad cardiovascular y cerebrovascular, según el tipo de antiagregantes plaquetarios y grupo dentario, así como la frecuencia de utilización de las medidas para su control. Métodos: Se efectuó un estudio observacional, descriptivo, longitudinal y prospectivo con un universo de 136 pacientes de más de 20 años, remitidos por su cardiólogo y que necesitaban realizarse extracciones dentarias sin modificar su tratamiento con antiagregantes plaquetarios. Las variables estudiadas fueron la enfermedad sistémica, el tipo de antiagregante plaquetario, el nivel de sangramiento, grupo dentario intervenido y método hemostático utilizado. Resultados: La mitad de los pacientes estudiados no presentó sangramiento posextracción dentaria. En los pacientes tratados con aspirina o clopidogrel predominaron los sujetos sin sangramiento para un 84,3 por ciento y 62,5 por ciento, respectivamente. En los de doble antiagregación prevaleció el sangramiento moderado con un 46,3 por ciento. Los grupos dentarios incisivo, canino y premolar no presentaron episodios de sangramiento para un 64,1 por ciento, 51,6 por ciento y 53,3por ciento, respectivamente. El método hemostático más utilizado fue la compresión de las corticales y termoterapia fría (47,8 por ciento). Conclusiones: La mitad de los pacientes con enfermedades cardiovasculares y cerebrovasculares no presentaron sangramiento posextracción dentaria(AU)

Introduction: The development of medical sciences brings with it an increase in life expectancy, together with the early detection of a large number of chronic diseases such as cerebrovascular and cardiovascular diseases, which are routinely treated with antiplatelet aggregation drugs. Knowledge on the treatment of these patients before stomatological surgical procedures constitutes a challenge in daily professional practice. Objective: To determine the level of bleeding after tooth extraction in patients with cardiovascular and cerebrovascular disease, according to the type of antiplatelet agents and dental group, as well as the frequency of use of measures for their control. Methods: An observational, descriptive, longitudinal and prospective study was carried out with a universe of 136 patients over 20 years of age, referred by their cardiologist, who needed dental extractions without modifying their treatment with antiplatelet agents. The variables studied were systemic disease, type of antiplatelet agent, level of bleeding, dental group treated and hemostatic method used. Results: Half of the patients studied did not present bleeding after tooth extraction. In patients treated with aspirin or clopidogrel, 84.3 percent and 62.5por ciento, respectively, had no bleeding. In those with double antiplatelet therapy, modera te bleeding prevailed with 46.3 The incisor, canine and premolar tooth groups did not present bleeding episodes (64.1 percent, 51.6and 53.3 percent respectively). The most commonly used hemostatic method was cortical compression and cold thermotherapy (47.8%). Conclusions: Half of the patients with cardiovascular and cerebrovascular diseases did not present bleeding after tooth extraction(AU)

Aspirin versus Rivaroxaban to Prevent Venous Thromboembolism after Total Knee Arthroplasty: A Double-blinded, Randomized Controlled Trial / Aspirina versus rivaroxabana na prevenção do tromboembolismo venoso após artroplastia total do joelho: Um ensaio clínico randomizado, controlado e duplo-cego

Abstract Objective Aspirin (acetylsalicylic acid, ASA) and rivaroxaban are anticoagulants that have increased in popularity due to ease of use in the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). The present study aimed to evaluate the efficacy of ASA compared with that of rivaroxaban on VTE prophylaxis in patients who underwent TKA. Method Forty patients who had primary knee osteoarthritis and would undergo TKA were randomized into two groups. In total, 20 patients in the ASA group used oral aspirin, at a dose of 300 mg/day, for VTE prophylaxis after TKA, while 20 patients in the rivaroxaban group received oral rivaroxaban, at a dose of 10 mg/day. On days 4 and 14 after the operation, deep vein thrombosis (DVT) in the lower limbs on the operated side was detected through duplex ultrasonography. Other complications were recorded for 14 days. Results There were no positive findings of DVT detected with duplex ultrasonography in the groups of patients, and the occurrence of pulmonary embolism was not observed. In total, 4 patients had subcutaneous ecchymosis on the fourth postoperative day (2 patients in the ASA group and 2 patients in the rivaroxaban group; p= 1.0), and another 4 patients on the fourteenth postoperative day (1 patient in the ASA group and 3 patients in the rivaroxaban group; p= 0.292). No cases of wound hematoma, major organ bleeding, wound infection, or reoperation were observed in the sample. Conclusion Aspirin and rivaroxaban had comparable efficacy to prevent VTE, without increasing the incidence of wound complications and bleeding after TKA.

Resumo Objetivo A aspirina (ácido acetilsalicílico, AAS) e a rivaroxabana são anticoagulantes que vêm ganhando popularidade devido à facilidade de uso na prevenção do tromboembolismo venoso (TEV) após artroplastia total do joelho (ATJ). Este estudo teve como objetivo avaliar a eficácia do AAS em comparação com a da rivaroxabana na profilaxia de TEV em pacientes submetidos a ATJ. Método Quarenta pacientes com osteoartrite primária do joelho, que seriam submetidos a ATJ, foram randomizados em dois grupos. No total, 20 pacientes do grupo AAS usaram aspirina oral, na dose de 300 mg/dia, para a profilaxia do TEV após ATJ; e 20 pacientes do grupo rivaroxabana receberam uma dose oral de 10 mg/dia. No 4° e 14° dias do pós-operatório, trombose venosa profunda (TVP) dos membros inferiores no lado da cirurgia foi detectada por meio de ultrassonografia duplex. Foram registradas outras complicações durante catorze dias. Resultados Não foram detectados achados positivos de TVP com a ultrassonografia duplex nos grupos de pacientes, e não se observou a ocorrência de embolia pulmonar. No total, 4 pacientes apresentaram equimose subcutânea no 4° dia do pós-operatório (2 pacientes no grupo AAS e 2 pacientes no grupo rivaroxabana; p= 1,0), e outros 4 pacientes, no 14° dia do pós-operatório (1 paciente no grupo AAS e 3 pacientes no grupo rivaroxabana; p= 0,292). Nenhum paciente da amostra apresentou hematoma da ferida cirúrgica, sangramento de órgão importante, infecção da ferida, ou necessidade de nova cirurgia. Conclusão A aspirina e a rivaroxabana apresentaram eficácia comparável na prevenção do TEV, sem aumentar a incidência de complicações da ferida e sangramento após ATJ.

Evidencias del Ácido Acetilsalicílico (Aspirina) en la prevención de la preeclampsia: revisión narrativa

Objetivo . Describir los métodos usados para predecir preeclampsia y cómo prevenirla usando ácido acetilsalicílico (aspirina) a dosis bajas de acuerdo con las recomendaciones de las principales organizaciones de ginecología y obstetricia. Metodología . Se realizaron búsquedas en PubMed y Cochrane Library desde el 1 de enero de 2020 al 1 de mayo de 2022, con los términos "pre-eclampsia", "trastornos hipertensivos en el embarazo" e "hipertensión y embarazo". Nos enfocamos en los análisis y recomendaciones de las más reconocidas organizaciones internacionales de ginecología y obstetricia, independiente del idioma original. Resultados . Para la predicción de preeclampsia se usan dos estrategias que pretenden encontrar la población con más riesgo basada en: 1) hallazgos clínicos de riesgo por condiciones antes del embarazo o propias del embarazo, y 2) un algoritmo de múltiples factores que incluye hallazgos clínicos, presión arterial, biomarcador y Doppler de arteria uterina. Usando ambas estrategias se encuentra efectividad variable de la aspirina en prevenir la preeclampsia. Se considera las dosis más efectivas entre 50 y 150 mg, siendo 81 mg la más recomendada en la actualidad. La dosis de 150 mg por día ha mostrado efectividad en la preeclampsia lejos del término; sin embargo, se considera que tiene más efectos secundarios. Conclusiones . Las más prestigiosas y reconocidas organizaciones de ginecología y obstetricia y de salud recomiendan aspirina a dosis bajas para prevenir la preeclampsia, preferiblemente al iniciar el segundo trimestre de gestación y mantenerla hasta las 36 a 37 semanas.

Objective: To describe the methods used to predict preeclampsia and how to prevent it using low-dose acetylsalicylic acid (aspirin) according to the recommendations of the main obstetrics and gynecology organizations. Methodology: We searched PubMed and Cochrane Library from January 1, 2020, to May 1, 2022, using the terms "pre-eclampsia", "hypertensive disorders in pregnancy" and "hypertension and pregnancy". We focused on the analyses and recommendations from the most recognized international obstetrics and gynecology organizations, independent of the original language. Results: For the prediction of preeclampsia, two strategies are used that aim to find the population at highest risk based on: 1) clinical findings of risk for pre-pregnancy or pregnancy conditions, and 2) a multi-factor algorithm that includes clinical findings, blood pressure, biomarker and uterine artery Doppler. Using both strategies, variable effectiveness of aspirin in preventing preeclampsia is found. The most effective dose range between 50-150 mg, with 81 mg being the most recommended at present. The dose of 150 mg per day has shown effectiveness in preeclampsia far from term; however, it is considered to have more side effects. Conclusions: The most prestigious and recognized obstetrics and gynecology and health organizations recommend low-dose aspirin to prevent preeclampsia, preferably at the beginning of the second trimester of pregnancy and maintained until 36-37 weeks.

Uso actual de la aspirina como agente antitrombótico: ¿droga vigente u obsoleta? / Present Use of Aspirin as an Antithrombotic Agent: Current or Outdated Drug?

RESUMEN El ácido acetilsalicílico, o aspirina, es una de las herramientas farmacológicas más usadas en el cuidado de los pacientes cardiovasculares. Durante años se utilizó ampliamente en prevención primaria y secundaria para disminuir el riesgo cardiovascular. En los últimos tiempos su uso ha sido cuestionado, con nuevos ensayos en diferentes escenarios dentro de la patología cardíaca, como la enfermedad vascular periférica, el accidente cerebrovascular, la prevención primaria en el contexto del tratamiento médico moderno, o en el paciente con un síndrome coronario agudo y necesidad concomitante de anticoagulación. A su vez, nuevos estudios cuestionan la necesidad de mantener la aspirina durante 12 meses junto a una tienopiridina luego de un síndrome coronario agudo, y proponen esquemas abreviados. En esta revisión, evaluamos la evidencia detrás de las indicaciones actuales del uso de aspirina en diferentes escenarios clínicos, y formulamos recomendaciones en cada uno de los casos.

ABSTRACT Acetylsalicylic acid, or aspirin, is one of pharmacological tools most widely used in the care of cardiovascular patients. For years, it has been widely used in primary and secondary prevention to reduce cardiovascular risk. Aspirin utilization has been questioned in recent times, with new trials in different scenarios of cardiovascular disease, such as peripheral vascular disease, stroke, primary prevention in the context of modern medical treatment, or in patients with acute coronary syndrome and concomitant need for anticoagulation. In turn, new studies question the need to maintain aspirin for 12 months together with a thienopyridine after an acute coronary syndrome, suggesting shorter regimens. In this review, we evaluate the evidence behind the current indications for aspirin use in different clinical scenarios and provide recommendations on a case-by-case basis.

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)

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

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)

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

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.

[Translated article] International Consensus Meeting on Venous Thromboembolism (ICM-VTE) after orthopedic procedures, any change in our clinical practice?

The International Consensus 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 strength 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.

Could Aspirin Treatment Modify the Assessment of the Uterine Arteries? / O tratamento com aspirina pode modificar a avaliação das artérias uterinas?

Abstract Objective To analyze whether acetylsalicylic (ASA) intake modifies the mean uterine arteries pulsatility index (UtA-PI) at the 2nd or 3rd trimester in a cohort of pregnant women with abnormal mean UtA-PI at between 11 and 14 weeks of gestation. Methods This is a retrospective cohort study. Singleton pregnancies with abnormal mean UtA-PI at between 11 and 14 weeks of gestation were studied. The participants were divided into 3 groups: 1) If the participant did not take ASA during pregnancy; 2) If the participant took ASA before 14 weeks of gestation; and 3) If the participant took ASA after 14 weeks of gestation. The mean UtA-PI was evaluated at the 2nd and 3rd trimesters, and it was considered to improve when it decreased below the 95th percentile. The prevalence ratio (PR) and the number needed to treat (NNT) werecalculated. Results A total of 72 participants with a mean UtA-PI>95th percentile at the 1st trimester of gestation were evaluated. Out of the 18 participants who took ASA, 8 participants started it before 14 weeks of gestation and 10 after. A total of 33.3% of these participants had improved the mean UtA-PI at the 2nd and 3rd trimesters of gestation, although it was not statistically significant (p=0.154). The prevalence ratio was 0.95 (95% confidence interval [CI]: 0.31-1.89), but between the 1st and 2nd trimesters of gestation, the PR was 0.92 (95%CI: 0.21-0.99) and it was statistically significant. Conclusion The present work demonstrates a modification of the mean UtA-PI in participants who took ASA compared with those who did not. It is important to check if ASA can modify the normal limits of uterine arteries because this could have an impact on surveillance.

Resumo Objetivo Analisar se a ingestão de acetilsalicílico (ASA) modifica o índice médio de pulsatilidade das artérias uterinas (UtA-PI) no 2° ou 3° trimestre em uma coorte de gestantes com média anormal de UtA-PI entre 11 e 14 semanas. Métodos Este é um estudo de coorte retrospectivo. Gravidezes únicas com média anormal de UtA-PI entre 11 e 14 semanas foram estudadas. As participantes foram divididas em 3 grupos: 1) Se a participante não tomou ASA durante a gravidez, 2) Se a participante tomou AAS antes das 14 semanas e 3) Se a participante tomou ASA após 14 semanas. A média do UtA-PI foi avaliada nos 2° e 3° trimestres e considerou-se que melhorava quando diminuía<95° percentil. Foram calculados a razão de prevalência (RP) e o número necessário para tratar (NNT). Resultados Foram avaliadas 72 participantes com média de UtA-PI>95° percentil no 1° trimestre de gravidez. Das 18 participantes que tomaram ASA, 8 participantes começaram antes de 14 semanas e 10 depois. Um total de 33,3% desses participantes melhoraram a média de UtA-PI nos 2° e 3° trimestres, embora não tenha sido estatisticamente significante (p=0,154). A razão de prevalência foi de 0,95 (intervalo de confiança [IC95%]: 0,31-1,89), mas entre os 1° e o 2° trimestres, a RP foi de 0,92 (IC95%: 0,21-0,99) e foi estatisticamente significativa. Conclusão O presente trabalho demonstra uma modificação da média de UtA-PI em participantes que faziam uso de ASA em comparação com aqueles que não faziam. É importante verificar se o ASA pode modificar os limites normais das artérias uterinas porque isso pode ter um impacto na vigilância.

Tratamiento farmacológico en la restricción del crecimiento fetal: revisión de la bibliografía / Pharmacological management for fetal growth restriction: literature review

Resumen OBJETIVO: Explorar las diferentes estrategias de tratamiento farmacológico de la restricción del crecimiento fetal propuestas a lo largo del tiempo. METODOLOGÍA: Revisión cuasi-sistemática de la evidencia científica histórica disponible acerca del tratamiento médico descrito para la atención de mujeres embarazadas con restricción del crecimiento fetal. RESULTADOS: Entre los tratamientos médicos descritos para tratar la restricción del crecimiento fetal, los donadores de óxido nítrico, las estatinas y la aspirina asociada con omega 3, han tenido desenlaces no consistentes en estudios con limitado tamaño de muestra. Por lo que se refiere a los inhibidores de la 5-fosfodiesterasa, el sildenafilo no se ha asociado con un aumento de la velocidad de crecimiento fetal pero sí con alarmas respecto de su seguridad debidas al incremento de los casos de hipertensión pulmonar fetal y mortalidad perinatal. Por su parte, el tadalafilo ha mostrado desenlaces iniciales favorables y se esperan estudios con mayor tamaño de muestra que permitan emitir recomendaciones claras con respecto a su indicación. También se esperan los desenlaces de estudios clínicos en curso, para definir la indicación de la heparina de bajo peso molecular en este escenario en virtud de sus prometedores resultados iniciales. Los procedimientos más invasivos, como la inyección de factor de crecimiento endotelial vascular y la plasmaféresis, permanecen en estudio como propuestas terapéuticas por los resultados de estudios preclínicos y clínicos con pocos pacientes. CONCLUSIÓN: Por ahora, ninguna estrategia farmacológica propuesta ha conseguido generar recomendaciones fuertes para su indicación; sin embargo, se esperan nuevos estudios con alta calidad metodológica que generen evidencia científica lo suficientemente contundente para recomendar su indicación.

Abstract OBJECTIVE: To explore the different pharmacological treatment strategies for fetal growth restriction proposed over time. METHODOLOGY: Quasi-systematic review of the available historical scientific evidence on the medical treatment described for the care of pregnant women with fetal growth restriction. RESULTS: Among the medical treatments described to treat fetal growth restriction, nitric oxide donors, statins, and aspirin associated with omega-3 have had inconsistent outcomes in studies with limited sample size. As for 5-phosphodiesterase inhibitors, sildenafil has not been associated with an increase in fetal growth velocity, but there have been alarms regarding its safety due to the increase in cases of fetal pulmonary hypertension and perinatal mortality. On the other hand, tadalafil has shown favorable initial outcomes and studies with a larger sample size are awaited to issue clear recommendations regarding its indication. The results of ongoing clinical studies are also awaited to define the indication of low molecular weight heparin in this setting, given its promising initial results. More invasive procedures, such as vascular endothelial growth factor injection and plasmapheresis, remain under study as therapeutic proposals due to the results of preclinical and clinical studies with few patients. CONCLUSION: For now, no proposed pharmacological strategy has managed to generate strong recommendations for its indication; however, new studies with high methodological quality are expected to generate scientific evidence strong enough to recommend its indication.