Fondaparinux versus Enoxaparin in the Treatment of Obese Patients with Acute Coronary Syndrome. / Fondaparinux versus Enoxaparina no Tratamento de Pacientes Obesos com Síndrome Coronariana Aguda.

BACKGROUND: Fondaparinux is an effective and safe anticoagulant in the treatment of acute coronary syndromes (ACS). However, due to the low representation of obese individuals in clinical trials, the effects of applying the results of this drug to this population remain uncertain. OBJECTIVES: To compare Fondaparinux to Enoxaparin in the treatment of obese patients with ACS. METHODS: This is a retrospective cohort study, including obese individuals (BMI ≥ 30 Kg/m2) admitted with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and treated with Fondaparinux or Enoxaparin between 2010 and 2020. The Fondaparinux and Enoxaparin groups were compared for their clinical and laboratory characteristics using chi-square and Mann-Whitney tests, as appropriate. The incidence of primary outcomes (death, reinfarction, stroke, major bleeding) was compared between groups. P-value < 0.05 was considered significant for all analyses. RESULTS: A total of 367 obese patients with NSTEMI or UA were included, of whom 258 used Fondaparinux and 109 used Enoxaparin. Mean age was 64 ± 12 years, and 52.9% were male. The prevalence of diabetes, hypertension, dyslipidemia, prior coronary artery disease, prior stroke, and implementation of invasive strategy was similar between groups. The incidence of the primary outcome was 4.7% in the Fondaparinux group and 5.5% in the Enoxaparin group (p = 0.729). There was no difference between groups when analyzing the components of the primary outcome separately. CONCLUSION: In a sample of obese patients with NSTEMI or UA, there was no difference in the occurrence of the composite outcome (death, stroke, reinfarction, major bleeding) between patients who used Fondaparinux or Enoxaparin.

FUNDAMENTO: O fondaparinux é um anticoagulante eficaz e seguro usado no tratamento de síndromes coronarianas agudas (SCAs). No entanto, devido à baixa representatividade de indivíduos obesos em ensaios clínicos, os efeitos de se aplicar os resultados desse medicamento nesta população continuam incertos. OBJETIVOS: Comparar o fondaparinux à enoxaparina no tratamento de obesos com SCA. MÉTODOS: Este é um estudo do tipo coorte retrospectivo, incluindo indivíduos obesos (IMC ≥ 30 Kg/m2) internados com Infarto do Miocárdio sem Elevação do Segmento ST (IAMSSST) ou Angina Instável (AI) e tratados com fondaparinux ou enoxaparina entre 2010 e 2020. Os grupos que receberam fondaparinux e enoxaparina foram comparados quanto suas características clínicas e laboratoriais usando o teste do qui-quadrado e o teste de Mann-Whitney, conforme apropriado. A incidência dos desfechos primários (morte, reinfarto, acidente vascular cerebral, sangramento maior) foi comparada entre os grupos. Um p<0,05 foi considerado estatisticamente significativo em todas as análises. RESULTADOS: Um total de 367 pacientes obesos com IAMSSST ou AI foi incluído, dos quais 258 usaram fondaparinux e 109 usaram enoxaparina. A idade média foi 64 ± 12 anos, 52,9% eram do sexo masculino. A prevalência e diabetes, hipertensão, dislipidemia, doença arterial coronariana prévia, acidente vascular cerebral prévio, e implementação de estratégia invasiva foi similar entre os grupos. A incidência do desfecho primário foi 4,7% no grupo fondaparinux e 5,5% no grupo enoxaparina (p = 0,729). Não houve diferença entre os grupos quando os componentes do desfecho primário foram analisados separadamente. CONCLUSÃO: Em uma amostra de pacientes obesos com IAMSSST ou AI, não houve diferença na ocorrência do desfecho composto (morte, acidente vascular cerebral, reinfarto, sangramento maior) entre os pacientes que utilizaram fondaparinux ou enoxaparina.

Clinical Impact of a Standardized Risk-Stratified Thromboprophylaxis Protocol for Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: To evaluate the clinical impact of an institutional thromboprophylaxis protocol in patients with multisystem inflammatory syndrome in children (MIS-C), who are at increased risk for thromboembolism (TE). STUDY DESIGN: We conducted a single-center retrospective cohort study of children less than 18 years between March 2020 and December 2021. Eligible patients were confirmed with MIS-C and were managed with a standardized multidisciplinary treatment approach that included a thromboprophylaxis protocol to guide and unify clinical practice. For high-risk patients, prophylactic dose enoxaparin (target anti-Factor Xa 0.1-0.3 U/mL) was added. In high-risk patients with TE risk factors persistent at hospital discharge, thromboprophylaxis was prescribed for an additional 30 days. RESULTS: Of 135 patients with MIS-C, 124 (92%) required intensive care unit stay and 64 (47%) required a central venous catheter for a median duration of 5 days (IQR, 4-7). Prophylactic dose enoxaparin was initiated in 116 out of 121 patients (96%) deemed high-risk per our protocol at a median of 1 day after admission [IQR, 0-3] achieving target levels at a median of 1 day [IQR, 1-2]. The median initial anti-Factor Xa level was 0.13 u/mL [IQR, 0.05-0.19]. One patient (0.7%) developed symptomatic noncatheter related superficial vein thrombosis requiring therapeutic anticoagulation. Thromboprophylaxis was extended for 30 days after discharge in 108 out of 135 patients (80%). Bleeding events occurred in 5 patients during hospitalization (4.2%). All bleeding events were clinically relevant nonmajor bleeding. There were no deaths. CONCLUSIONS: Implementation of an institutional standardized thromboprophylaxis protocol in MIS-C was feasible and led to timely initiation of prophylactic anticoagulation and low rates of TEs and bleeding complications.

Effect of protection of enoxaparin against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

OBJECTIVE: The study aimed to investigate the protection of enoxaparin (E) against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries on in vitro fertilization outcomes. METHODS: In total, 56 adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham+E, I+E, and I/R+E. Ischemia groups were subjected to bilateral adnexal torsion for 3 h. In contrast, I/R and I/R+E groups received subsequent detorsion for 3 h. Enoxaparin (0.5 mg/kg s.c.) was administered 30 min prior to ischemia (I+platelet-rich plasma) or reperfusion (I/R+I+platelet-rich plasma). Ovaries were stimulated through intraperitoneal injection of 150-300 internal units IU/kg pregnant mare serum gonadotropin. Anti-Müllerian hormone levels were measured before and after surgery in all groups. RESULTS: When the number of metaphase II oocytes was evaluated, statistically significant differences were observed between the I and I+E (p=0.001) and I/R and I/R+E (p=0.000) groups. When both I and I+E groups and I/R and I/R+E groups were compared, it was found that E application increased the number of fertilized oocytes. The number of embryos on the second day was higher in the I/R+E group than that in the I/R group. Statistically significant differences were found in the number of grade 1 embryos between the I/R and I/R+E groups (p=0.003). In comparing anti-Müllerian hormone values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: Enoxaparin effectively minimizes ovarian damage and preserves ovarian reserve following ovarian torsion.

Administration of Prophylactic Enoxaparin on the Morning of Surgery Does Not Increase Risk of Blood Transfusion or Wound Drainage Following Internal Fixation of Geriatric Femur Fractures.

BACKGROUND: Despite standard use of chemoprophylaxis, 30-day incidence of venous thromboembolism after geriatric, those older than 60 years, femur fracture surgery is reported to be up to 10%. Missing one dose of enoxaparin has been proven to increase the risk of developing venous thromboembolism. It is commonplace to hold preoperative chemoprophylaxis the morning of surgery because of concern for intraoperative bleeding or wound drainage. We sought to determine whether administration of prophylactic enoxaparin the morning of surgery resulted in an increased rate of blood transfusion or wound drainage in geriatric patients undergoing femur fracture treatment. METHODS: We retrospectively reviewed patients older than 60 years who underwent internal fixation of an isolated femur fracture, including femoral neck, intertrochanteric, subtrochanteric, femoral shaft, and distal femur fractures, at a Level 1 trauma center. Medical records, hospital billing data, and radiographs were reviewed to determine patient characteristics such as Charlson Comorbidity Index, enoxaparin dosing, packed red blood cell transfusion, and persistent wound drainage, defined as any drainage requiring utilization of closed incision negative pressure wound therapy. Thirty-day mortality served as the secondary outcome measure. RESULTS: Five hundred seven patients were included. One hundred sixty-four (32%) received enoxaparin on the morning of surgery, whereas 343 (68%) did not. 27% of patients received PRBC transfusion, and this did not differ between groups (27% vs. 28%, P = 0.72). Subgroup analysis of fixation strategies revealed no difference in the frequency of blood transfusion for any fixation type as related to the timing of enoxaparin dosage. Utilization of closed incision negative pressure wound therapy for the treatment of postoperative wound drainage did not differ between dosing groups. No difference was observed in thirty-day mortality between groups (2.4% vs. 2.7%, P = 0.9). DISCUSSION: Administration of a prophylactic dose of enoxaparin on the morning of surgery does not seem to increase the rate of postoperative blood transfusion or wound drainage after fixation of geriatric femur fracture. LEVEL OF EVIDENCE: Level III, therapeutic.

Rabdomiossarcoma de ovário em paciente jovem: Relato de caso / Ovarian rhabdomyosarcoma in a young patient: report of case

O sarcoma de partes moles mais comum na infância é o rabdomiossarcoma. Entretanto a localização ovariana é extremamente rara. Acredita-se que este tumor se origina de células imaturas destinadas a compor o músculo esquelético, porém pode surgir em locais onde tipicamente não há músculo esquelético. O diagnóstico do Rabdomiossarcoma primário de ovário pode causar um dilema entre os clínicos, cirurgiões e patologistas, por se tratar de um tumor muito raro. Após o diagnóstico, é necessária a investigação de possíveis metástases. Este caso trata de uma paciente de 17 anos, submetida a parto cesáreo e, no intraoperatório, foi observado aumento de volume, inespecífico, de ovário direito sendo optado por não abordar naquele momento. De antecedentes pessoais, apresentava ooforectomia esquerda aos 13 anos, por Tumor de células da granulosa juvenil e lobectomia inferior esquerda por malformação adenomatosa cística aos 7 anos. Deu entrada no Pronto Socorro 17 dias após dar à luz com queixa de febre, vômitos e dor abdominal. Foi realizada ultrassonografia de urgência, onde foi visualizada massa sólida em fossa ilíaca direita medindo 14,0 x 11,2 x 10,8 cm. Realizada laparotomia exploradora com anexectomia direita e cito-redução subótima do tumor. O resultado anátomo-patológico demonstrou neoplasia maligna fusocelular com áreas de necrose em ovário. A complementação com o estudo imunohistoquímico concluiu rabdomiossarcoma embrionário. Ela voltou a procurar atendimento no Pronto Socorro dois meses após a abordagem com queixa de vômitos biliosos e epigastralgia. Realizou tomografia computadorizada que identificou recidiva do tumor. Durante a internação, evoluiu com quadro de tromboembolismo pulmonar agudo. Diante disso, foi iniciada terapia com enoxaparina em dose plena e quimioterapia com esquema VAC (Vincristina, Doxorrubicina e Ciclofosfamida). Entretanto, ela apresentou insuficiência de múltiplos órgãos, que culminou com o óbito da paciente. O curso clínico desse caso mostra a rápida progressão e letalidade dessa neoplasia. Além da histopatologia, a idade, o tamanho do tumor, a ressecabilidade, o subtipo histopatológico, a presença de metástase no momento do diagnóstico e a invasão linfonodal influenciam no curso clínico da doença. Palavras-chave: Neoplasias ovarianas. Rabdomiossarcoma. Ovário.

Superior ophthalmic vein and cavernous sinus thrombosis associated with COVID-19: a case report / Trombose de veia oftálmica superior e seio cavernoso associada à COVID-19: relato de caso

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.

RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.

Eficácia, segurança e tolerabilidade da Enoxaparina para prevenção de tromboembolismo venoso nas cirurgias eletivas de abdome, pelve e varizes: revisão rápida de evidências / Seffectiveness,safety and tolerability of Enoxaparin for the prevention of venous thromboembolism in elective surgery of the abdomen, pelvis and varices: quick evidence review

Tecnologia: Enoxaparina comparada à profilaxia mecânica e/ou outros medicamentos disponíveis ou não no SUS. Indicação: Profilaxia de Tromboembolismo Venoso (TEV) em pacientes submetidos a cirurgia de abdome, pelve e varizes. Pergunta: Há superioridade em eficácia e segurança da enoxaparina (heparina de baixo peso molecular - HBPM) comparada à profilaxia mecânica e a outros medicamentos disponíveis ou não no SUS para prevenção de TEV em pacientes acima de 18 anos, não gestantes, em pós-operatório de cirurgias eletivas de abdome, pelve e varizes? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas quatro e incluídas duas revisões sistemáticas com metanálise. Conclusão: HBPM no pós-operatório de cirurgia abdominal e pelve reduziu a incidência de TEV geral e TEV sintomático, sem aumentar risco de sangramento e mortalidade. Nas cirurgias de veias varicosas, foi observado uma redução de todos os eventos trombóticos e risco de TVP, sem aumentar risco de sangramento

Technology: Enoxaparin compared to mechanical prophylaxis and/or other drugs available or not in the SUS. Indication: Prophylaxis of Venous Thromboembolism (VTE) in patients undergoing surgery of the abdomen, pelvis and varicose veins. Question: There is superiority in efficacy and safety of enoxaparin, compared to mechanical prophylaxis and other drugs available or not in the SUS, for the prevention of VTE for patients over 18 years old, non-pregnant in the postoperative period of elective surgeries of the abdomen, pelvis and varicose veins? Methods: Rapid review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: Four were selected and two systematic reviews with meta-analysis were included. Conclusion: LMWH in the postoperative period of abdominal and pelvic surgery reduced the incidence of general VTE and symptomatic VTE, without increasing the risk of bleeding and mortality. In varicose vein surgeries, a reduction in all thrombotic events and risk of DVT was observed, without increasing the risk of bleeding

Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial : Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial).

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

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

Síndrome inflamatorio multisistémico asociado a COVID-19: a propósito de un caso clínico con fenotipo shock e íleo paralítico / Multisystem inflammatory syndrome associated with COVID-19: clinical case with shock phenotype and paralytic ileus / Síndrome inflamatória multissistêmica associada à COVID-19: relato de caso com fenótipo de choque e íleo paralítico

La enfermedad por coronavirus 2019 (COVID-19) causada por la infección por SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) se ha extendido por todo el mundo desde diciembre de 2019. Luego de la primera ola de COVID-19, se reporta por primera vez en mayo de 2020 en el Reino Unido un estado hiperinflamatorio asociado temporalmente a la infección por SARS-CoV-2 en un grupo de niños ingresados a unidades de cuidado intensivo pediátrico. Este nuevo fenotipo, con características similares a la enfermedad de Kawasaki y al síndrome del shock tóxico, se ha denominado síndrome inflamatorio multisistémico en niños (MIS-C). Es fundamental la sospecha y el reconocimiento tempranos de esta entidad, con el fin de ofrecer un tratamiento médico oportuno, para prevenir la muerte y el desarrollo de secuelas. Presentamos el caso de una preescolar de 5 años, en la que se realizó diagnóstico de MIS-C con un fenotipo shock e íleo paralítico.

The coronavirus disease 2019 (COVID-19) caused by the infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread worldwide since December 2019. After the first wave of COVID-19, a hyperinflammatory condition temporarily associated with SARS-CoV-2 infection appeared in a group of children admitted to pediatric intensive care units and reported for the first time in May 2020 in the United Kingdom. This new phenotype shared characteristics with the Kawasaki disease and toxic shock syndrome and has been called multisystem inflammatory syndrome in children (MIS-C). Early suspicion and recognition of this condition is key in order to offer timely medical treatment to prevent death and the development of sequelae. We present the case of a 5-year-old child, in which diagnosis of MIS-C with a shock phenotype and paralytic ileus.

A doença de coronavírus 2019 (COVID-19) causada pela infecção por SARS-CoV-2 (síndrome respiratória aguda grave coronavírus 2) se espalhou pelo mundo desde dezembro de 2019. Após a primeira onda de COVID-19, houve relatos pela primeira vez em maio de 2020 no Reino Unido duma doença hiperinflamatória temporariamente associada à infecção por SARS-CoV-2 num grupo de crianças internadas em unidades de terapia intensiva pediátrica. Esse novo fenótipo com características semelhantes à doença de Kawasaki e a síndrome do choque tóxico foi chamado de síndrome inflamatória multissistêmica em crianças (MIS-C). A suspeita precoce e o reconhecimento dessa entidade são essenciais, a fim de oferecer tratamento médico oportuno, para prevenir a morte e o desenvolvimento de sequelas. Apresentamos o caso de uma menina pré-escolar de 5 anos que foi diagnosticada com MIS-C com fenótipo de choque e íleo paralítico.

Reporte de caso: trombosis cerebral en el embarazo / Case report: cerebral thrombosis in pregnancy

La trombosis venosa cerebral en el embarazo se manifiesta como un accidente vascular cerebral de tipo venoso, infrecuente. El diagnóstico y tratamiento anticoagulante precoz disminuye la morbimortalidad. El objetivo de este trabajo de investigación es describir los signos, síntomas y estudios complementarios que guiaron al diagnóstico y tratamiento del caso, trombosis cerebral en el embarazo, de una paciente en el consultorio Conmed, La Paz ­ Bolivia, en el año 2021. El caso trata de una mujer de 32 años de edad en periodo de gestación, refiere presentar hace 1 semana cefalea, náuseas y vómitos, presenta desvanecimiento quedando somnolienta, el examen físico indica compromiso neurológico, motivo de su internación. El hemograma reporta anemia; la TC y RM de cráneo imagen nodular focal hipodensa en región frontal derecha y área hiperintensa en seno longitudinal superior, respectivamente; indicando sospecha de trombosis venosa del seno longitudinal superior. Se empieza tratamiento profiláctico con enoxaparina evolucionando favorablemente. Se realiza una venorresonancia confirmando el diagnostico, continuando tratamiento con enoxaparina. Las manifestaciones clínicas son diversas, siendo las más comunes: Cefalea, náuseas, vómitos. El criterio estándar para diagnosticar trombosis venosa cerebral es la combinación de imagen por resonancia magnética y la venografía por resonancia magnética. La anticoagulación (enoxaparina) es la terapia de primera línea en el manejo de trombosis venosa cerebral en el embarazo. En conclusión, la trombosis venosa cerebral es una entidad infrecuente, con manifestaciones clínicas variables; la tomografía, resonancia magnética, venorresonancia determinan el diagnóstico definitivo y la anticoagulación (enoxaparina) es el tratamiento de primera línea.

Thromboprophylaxis with unilateral pneumatic device led to less edema and blood loss compared to enoxaparin after knee arthroplasty: randomized trial.

BACKGROUND: Pharmacological and mechanical thromboprophylaxis are frequently used together after total knee arthroplasty (TKA). Most studies in this context compare anticoagulants versus a combination of these drugs with an intermittent pneumatic compression device (IPCD). However, there is uncertainty about the need for the combination of both and whether a unilateral IPCD would alone affect other important clinical outcomes: edema and blood loss. We compared the effects of enoxaparin versus unilateral portable IPCD after TKA on edema and blood loss. We hypothesised that unilateral IPCD would cause the same level of edema and the same blood loss as enoxaparin. METHODS: In this open, randomized trial (1:1), adults with no history of coagulation disorders, anticoagulant use, venous thromboembolism, liver or malignant diseases underwent TKA. For 10 days, participants received the IPCD, used 24 h/day on the operated leg from the end of surgery, or 40 mg of enoxaparin, starting 12 h after surgery. All underwent the same rehabilitation and were encouraged to walk on the same day of surgery. We measured edema (thigh, leg and ankle circumference) before and on the third postoperative day. Blood loss (volume accumulated in the suction drain and drop of hemoglobin and hematocrit in 48 h) was a secondary outcome. RESULTS: We randomized 150 patients and lost 3 to follow-up with enoxaparin and 2 with IPCD. There was no case of symptomatic venous thromboembolism. Four patients needed transfusions (three receiving enoxaparin), one had infection and one hemarthrosis (both in the enoxaparin group). Leg circumference increased by approximately 2 cm for enoxaparin group and 1.5 cm in IPCD (p <  0.001). The increase in ankle circumference was about 1.5 cm in the enoxaparin group (p <  0.001), and almost zero in IPCD (p = 0.447). Enoxaparin group lost 566.1 ml (standard deviation, SD, 174.5) of blood in the first 48 h, versus 420.8 ml (SD 142.5) in the IPCD. CONCLUSIONS: Exclusively mechanical prophylaxis after TKA with portable IPCD only on the operated leg reduces leg and ankle swelling and post-operative blood loss compared to exclusively pharmacological prophylaxis with enoxaparin. Portable devices that can prevent deep vein thrombosis and pulmonary embolism without increasing blood loss or other risks should be further investigated. TRIAL REGISTRATION: REBEC RBR-8k2vpx. Registration date: 06/04/2019.

[Comment on article "Enoxaparin dose associated with decreased risk of death in COVID-19"]. / Comentario al artículo "Dosis de enoxaparina asociada a disminución de riesgo de muerte en COVID-19".

In this letter to the editor, apropos of the article "Enoxaparin dose associated with decreased risk of death in COVID-19", it is discussed the role of the current thromboprophylactic strategies, as well as the potential role of heparins in the management of COVID-19.

En la presente carta al editor, a propósito del artículo "Dosis de enoxaparina asociada a disminución de riesgo de muerte en COVID-19", se discute el papel de las estrategias de tromboprofilaxis y el potencial rol de las heparinas en relación con la COVID-19.

Thromboprophylaxis of Patients Submitted to Total Hip and Knee Arthroplasty: A Cost-Effectiveness Assessment From the Perspective of the Brazilian National Health System.

OBJECTIVES: Venous thromboembolism (VTE) is a serious national and international public health issue. Major orthopedic surgeries, such as a total hip (THA) and knee (TKA) arthroplasties, are associated with an increased risk of VTE, long-term complications, functional disability, and death resulting from hypercoagulability by surgical trauma. This pharmacoeconomic analysis aimed to identify the most cost-effective anticoagulant alternative in preventing VTE in patients undergoing THA and TKA. METHODS: A decision tree model was developed, comparing direct oral anticoagulants (rivaroxaban, apixaban, and dabigatran) with enoxaparin, with separate THA and TKA models a 3-month time horizon from the perspective of the Brazilian National Health System. The results were presented as incremental cost-effectiveness ratio (ICER), and the outcomes analyzed were avoided complications (ACs) after thromboprophylaxis. Comparative effectiveness was obtained from a published meta-analysis. A willingness to pay value of approximately R$ 15 000.00 was used per AC, and a probabilistic sensitivity analysis with the Monte Carlo simulation was conducted. RESULTS: Apixaban was the anticoagulant that presented the best ICER for patients undergoing THA (R$ 207.52/AC) and TKA (R$ 133.59/AC), followed by rivaroxaban (R$ 347.21/AC), dabigatran (R$ 372.56/AC), and enoxaparin (R$ 711.44/AC) for THA and by dabigatran (R$ 194.07/AC), rivaroxaban (R$ 221.12/AC), and enoxaparin (R$ 747.25/AC) for TKA. After ICER analysis, apixaban prevails over the other technologies analyzed for both surgical procedures, confirmed after sensitivity analysis. CONCLUSION: Our model suggests that, in the Brazilian National Health System, apixaban is the most cost-effective alternative in preventing VTE after THA and TKA.

In Silico Analysis of the Antagonist Effect of Enoxaparin on the ApoE4-Amyloid-Beta (Aß) Complex at Different pH Conditions.

Apolipoprotein E4 (ApoE4) is thought to increase the risk of developing Alzheimer's disease. Several studies have shown that ApoE4-Amyloid ß (Aß) interactions can increment amyloid depositions in the brain and that this can be augmented at low pH values. On the other hand, experimental studies in transgenic mouse models have shown that treatment with enoxaparin significantly reduces cortical Aß levels, as well as decreases the number of activated astrocytes around Aß plaques. However, the interactions between enoxaparin and the ApoE4-Aß proteins have been poorly explored. In this work, we combine molecular dynamics simulations, molecular docking, and binding free energy calculations to elucidate the molecular properties of the ApoE4-Aß interactions and the competitive binding affinity of the enoxaparin on the ApoE4 binding sites. In addition, we investigated the effect of the environmental pH levels on those interactions. Our results showed that under different pH conditions, the closed form of the ApoE4 protein, in which the C-terminal domain folds into the protein, remains stabilized by a network of hydrogen bonds. This closed conformation allowed the generation of six different ApoE4-Aß interaction sites, which were energetically favorable. Systems at pH5 and 6 showed the highest energetic affinity. The enoxaparin molecule was found to have a strong energetic affinity for ApoE4-interacting sites and thus can neutralize or disrupt ApoE4-Aß complex formation.

[Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis]. / Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular.

Despite standard thromboprophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian confluent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

A pesar de la tromboprofilaxis estándar, el diagnóstico de tromb osis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en confluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

New generation oral anticoagulant apixaban enhances embryo implantation by increasing integrin ß3 expression in rats: A pilot study.

OBJECTIVE: The first aim of this study was to investigate the effect of apixaban on endometrial receptivity via immunohistochemical investigation of integrin ß3 expression in pregnant rats. The second aim was to compare the endometrial effects of both subcutaneous and oral anticoagulant drugs in terms of integrin ß3 expressions. METHODS: A total of 24 rats were selected for this study and divided into three equal groups as control, enoxaparin and apixaban groups. Subcutaneous enoxaparin and oral apixaban were applied for 15 days starting on the first day of pregnancy. On the 15th day of pregnancy, all rats were killed by cervical dislocation, and uterine horns, including pregnancy materials, were investigated for pregnancy success and endometrial receptivity by using immunohistochemical integrin ß3 staining. RESULTS: Living, viable fetuses were higher in the apixaban group compared to the control group (p=0.037). Intensity and universality of immunohistochemical staining of integrin ß3 for endometrial stroma were detected statistically higher in the apixaban group than the other groups. (p=0.009 for intensity, p=0.014 for universality). Endometrial epithelial and myometrial integrin ß3 expression were detected to be identical between the groups (p=0.3). CONCLUSIONS: Apixaban enhances endometrial receptivity via increasing integrin ß3 expression in rats. This result can lead to further studies to be done in the future.

[Enoxaparin dose associated with decreased risk of death in COVID-19]. / Dosis de enoxaparina asociada a disminución de riesgo de muerte en COVID-19.

Background: In December 2019, an outbreak of COVID-19 was reported for the first time. This disease has caused millions of deaths worldwide. To date multiple drugs have been tried, without finding an effective treatment yet. Objective: To describe the evolution and the pharmacological treatment used in patients hospitalized due to COVID-19. Material and methods: Observational study in 200 patients hospitalized due to COVID-19 in a regional hospital of Acapulco who were admitted between March and July 2020. The characteristics, pharmacological treatment and evolution of the patients were identified. Univariate, bivariate and multivariate analyses were performed. Results: 60% of the patients were male, 83% had at least one comorbidity, 56% died. The most used drug was enoxaparin, of which receiving a 60 mg dose was associated with a lower risk of death, compared to receiving 40 mg. Having received hydroxychloroquine, methylprednisolone, moxifloxacin and being 60 years or older was associated with a higher risk of progressing to death. Conclusions: There was a high mortality. The most used drug was enoxaparin, of which using doses of 60 mg reduced the risk of death.

Introducción: en diciembre de 2019 se reportó por primera vez un brote de COVID-19. Esta enfermedad ha ocasionado millones de muertes a nivel mundial. A la fecha se han probado multiples fármacos, sin encontrar un tratamiento eficaz aún. Objetivo: describir la evolución y el tratamiento farmacológico utilizado en pacientes hospitalizados por COVID-19. Material y métodos: estudio observacional en 200 pacientes hospitalizados por COVID-19 en un hospital regional de Acapulco que ingresaron entre marzo y julio de 2020. Se identificaron las características, el tratamiento farmacológico y la evolución de los pacientes. Se realizó analisis univarido, bivariado y multivariado. Resultados: el 60% de los pacientes fueron del sexo masculino, 83% presentaron al menos una comorbilidad, 56% fallecieron. El fármaco más utilizado fue la enoxaparina, del cual recibir dosis de 60 mg se asoció a menor riesgo de fallecer comparado con recibir 40 mg. Haber recibido hidroxicloroquina, metilprednisolona, moxifloxacino y tener 60 años o más se asoció a un mayor riesgo de morir. Conclusiones: se presentó una elevada mortalidad. El fármaco más utilizado fue la enoxaparina, del cual utilizar dosis de 60 mg disminuyó el riesgo de fallecer.

Nebulization with alkaline hipertonic ibuprofen induces a rapid increase in platelets circulating in COVID-19 patients but not in healthy subjects.

We analyze changes in circulating platelets in COVID-19 positive patients who received conventional treatment Dexamethasone and Enoxaparin (Dexa-Enoxa) compared to patients treated with conventional therapy plus nebulization with alkaline hypertonic ibuprofenate (AHI). Results show that after 24 h of nebulization with AHI, circulating platelets shows an increase about 40% at 24 h and reach 65% at 96 h. In patients with platelets content below 200,000 by microliter the increase was 49% and 79% at 24 and 96 h respectively. In patients with platelets above 200,000 by microliter the increase was 24% and 31% at 24 and 96 h, respectively. The increase of platelets via AHI was similar in both, men and women.To evaluate whether this action of AHI was related to platelets from COVID-19 positive patients or also for healthy people, two controls were included: one of them with 10 healthy volunteers and another one with COVID-19 positive patients hospitalized and treated only with Dexa-Enoxa. Results show that, in healthy volunteers, the number of circulating platelets remains unchanged even after 7 days of treatment with AHI. In COVID-19 positive patients treated only with Dexa-Enoxa for 4 days, platelets increased only 16%.

Dosis de enoxaparina asociada a disminución de riesgo de muerte en COVID-19 / Enoxaparin dose associated with decreased risk of death in COVID-19

Introducción: en diciembre de 2019 se reportó por primera vez un brote de COVID-19. Esta enfermedad ha ocasionado millones de muertes a nivel mundial. A la fecha se han probado multiples fármacos, sin encontrar un tratamiento eficaz aún. Objetivo: describir la evolución y el tratamiento farmacológico utilizado en pacientes hospitalizados por COVID-19. Material y métodos: estudio observacional en 200 pacientes hospitalizados por COVID-19 en un hospital regional de Acapulco que ingresaron entre marzo y julio de 2020. Se identificaron las características, el tratamiento farmacológico y la evolución de los pacientes. Se realizó analisis univarido, bivariado y multivariado. Resultados: el 60% de los pacientes fueron del sexo masculino, 83% presentaron al menos una comorbilidad, 56% fallecieron. El fármaco más utilizado fue la enoxaparina, del cual recibir dosis de 60 mg se asoció a menor riesgo de fallecer comparado con recibir 40 mg. Haber recibido hidroxicloroquina, metilprednisolona, moxifloxacino y tener 60 años o más se asoció a un mayor riesgo de morir. Conclusiones: se presentó una elevada mortalidad. El fármaco más utilizado fue la enoxaparina, del cual utilizar dosis de 60 mg disminuyó el riesgo de fallecer

Background: In December 2019, an outbreak of COVID-19 was reported for the first time. This disease has caused millions of deaths worldwide. To date multiple drugs have been tried, without finding an effective treatment yet. Objective: To describe the evolution and the pharmacological treatment used in patients hospitalized due to COVID-19. Material and methods: Observational study in 200 patients hospitalized due to COVID-19 in a regional hospital of Acapulco who were admitted between March and July 2020. The characteristics, pharmacological treatment and evolution of the patients were identified. Univariate, bivariate and multivariate analyses were performed. Results: 60% of the patients were male, 83% had at least one comorbidity, 56% died. The most used drug was enoxaparin, of which receiving a 60 mg dose was associated with a lower risk of death, compared to receiving 40 mg. Having received hydroxychloroquine, methylprednisolone, moxifloxacin and being 60 years or older was associated with a higher risk of progressing to death. Conclusions: There was a high mortality. The most used drug was enoxaparin, of which using doses of 60 mg reduced the risk of death