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

SUMMARY 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.

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

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

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

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

Caracterización de una población pediátrica seguida en una clínica de anticoagulación / Description of a pediatric population followed at an anticoagulation clinic

Resumen Introducción: En la población pediátrica, el 95% de las tromboembolias venosas son secundarias a un factor de riesgo; la presencia de catéter venoso central es el factor de riesgo más importante para el desarrollo de trombosis venosa profunda en esta población. Los estudios en población adulta sobre el uso de anticoagulantes se han extrapolado a la población pediátrica, y por ello es importante tener en cuenta las características diferenciales entre ambas poblaciones. Método: Se realizó un estudio descriptivo en el que se revisaron 2300 registros clínicos de pacientes seguidos por la Clínica de Anticoagulación institucional desde 2011 hasta 2019, buscando identificar pacientes menores de 18 años que hubieran recibido manejo anticoagulante ambulatorio. Resultados: Se encontraron 43 pacientes menores de 18 años, el 60% de sexo femenino, con una edad promedio de 9.8 ± 5.2 años. El antecedente patológico más prevalente fueron las valvulopatías (28%). Las principales indicaciones para recibir manejo anticoagulante incluyeron cardiopatías congénitas (21%), prótesis valvular cardíaca mecánica (21%, 5 aórticas y 4 mitrales) y trombosis venosa profunda (14%). La warfarina se utilizó en el 72% de los pacientes. El 81% de los pacientes recibieron tratamiento anticoagulante extendido. Las principales complicaciones durante el tratamiento anticoagulante fueron sangrado ginecológico y cutáneo, así como trombocitopenia. Conclusiones: Las cardiopatías congénitas y las valvulopatías cardíacas son las principales indicaciones para considerar el manejo anticoagulante en la población pediátrica. La warfarina es el medicamento más utilizado en forma ambulatoria en esta población. La adherencia adecuada y el seguimiento ambulatorio en esta población requieren herramientas adicionales para lograr un excelente tratamiento anticoagulante.

Abstract Introduction: In pediatric patients, 95% of venous thromboembolisms are secondary to a risk factor; the presence of central venous catheter is the most important risk factor for the development of deep vein thrombosis in this population. Studies about anticoagulation treatment in adult patients have been extrapolated to the pediatric population, it is important to consider the differential characteristics between these two populations. Method: A descriptive study was conducted; there were reviewed 2300 clinical records of patients followed by the institutional anticoagulation clinic from 2011 to 2019, looking for underage patients who have received ambulatory anticoagulation treatment management. Results: 43 patients under the age of 18 years old were found. 60% were female and the average age was 9.8 ± 5.2 years. The most prevalent pathological antecedent was valve disease (28%). The main indications for anticoagulant treatment included congenital heart disease (21%), mechanical heart valves (21%, 5 aortic and 4 mitral) and deep vein thrombosis (14%). Warfarin was found in 72% of patients. 81% of patients received extended anticoagulation therapy. The main complications during anticoagulant treatment included gynecological and cutaneous bleeding, as well as thrombocytopenia. Conclusions: Congenital heart disease and heart valve disease are the main indications for considering anticoagulation treatment in the pediatric population. Warfarin is the most formulated anticoagulant in this outpatient population. Adequate adherence and outpatient follow-up in requires additional tools to achieve excellent anticoagulant treatment.

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

Hiponatremia e hiperpotasemia persistente inducida por enoxaparina y revertida con hidrocortisona en paciente con metástasis lumbares / Low molecular weight heparin-induced hyperkalemia and hyponatremia: report of one case

Low molecular weight heparin-induced hyperkalemia is not an uncommon side effect. The development of hyponatremia is well described although it is less common. We report a 72-year-old woman with lumbar metastases who developed hyponatremia and hyperkalemia on the tenth day of hospitalization. Hyponatremia, with limited criteria for syndrome of inappropriate secretion of antidiuretic hormone, did not resolve with vigorous volume restriction. Hyperkalemia without an acid-base disorder or baseline renal failure, did not resolve after losartan was stopped. Enoxaparin-induced hypoaldosteronism was proposed and the drug was discontinued. After four days' persistence of the electrolyte disturbance, dexamethasone was changed to Hydrocortisone, and parameters normalized in 24 hours. The patient remained well until discharge and during outpatient control.

Efficacy and Safety of Rivaroxaban versus Enoxaparin in the Treatment of Malignant Tumor Complicated with Venous Thromboembolism ：A Meta-analysis / 中国药房

OBJECTIVE：To compare the eff icacy and safety of rivaroxaban versus enoxaparin in the treatment of malignant tumor complicated with venous thromboembolism （VTE），and to provide evidence-based reference to the clinic. METHODS ： Retrieved from PubMed ，Embase，Cochrane Library ，Clinical Trials ，CNKI，CBM and VIP ，clinical trials or observational studies about rivaroxaban versus enoxaparin were collected during the inception to Apr. 2020. After literature screening and data extraction ， the quality of included literatures were evaluated by Newcastle Ottawa scale ；Stata 15.0 software was used to conduct Meta-analysis，sensitivity analysis and publication bias analysis. RESULTS ：A total of 5 observational clinical cohort studies were retrieved，including 4 retrospective cohort studies and one prospective cohort study. Totally 997 patients were included ，among which 625 patients received enoxaparin and 372 patients received rivaroxaban. Results of Meta-analysis showed that there was no statistical significance in recurrence rate of VTE at 3 months follow-up [RR ＝0.91，95％CI（0.50，1.66），P＝0.760] and 6 months follow-up [RR ＝0.53，95％CI（0.24，1.15），P＝0.106] as well as the incidence of massive hemorrhage at 3 months follow-up [RR ＝ 1.22 ，95％CI（0.66，2.25），P＝0.530] and 6 months follow-up [RR ＝1.30，95％CI（0.73，2.33），P＝0.368]. The results of sensitivity analysis showed that the results of above Meta-analysis were stable ；the results of publication bias analysis showed that there was less possibility of publication bias in this study. CONCLUSIONS ：Rivaroxaban is as effective and safe as enoxaparin in the treatment of malignant tumor with VTE.

Hemorragia adrenal bilateral sin insuficiencia adrenal asociada con enoxaparina. Reporte de caso / Bilateral adrenal hemorrhage without adrenal insufficiency associated with enoxaparin. usage: case report

RESUMEN La hemorragia adrenal bilateral es un fenómeno poco común que puede acarrear consecuencias catastróficas por una crisis adrenal. Se ha asociado con diversas entidades como la sepsis, anticoagulación, neoplasias, el trauma, síndrome antifosfolípido y estado postoperatorio, especialmente, de cirugías ortopédicas. Su diagnóstico se dificulta en la medida en que los pacientes presentan signos y síntomas inespecíficos, por lo cual, una alta sospecha clínica es el principal indicador para la realización de una imagen que confirme el dictamen. Se presenta el caso de una hemorragia adrenal bilateral sin insuficiencia adrenal en una mujer de 71 años que, durante el quinto día del posoperatorio, tras una osteosíntesis de rodilla y recibiendo profilaxis antitrombótica con enoxaparina, ingresa al servicio de urgencias por dolor abdominal tipo cólico con 12 horas de evolución, acompañado de náuseas y sin signos de inestabilidad hemodinámica.

SUMMARY Bilateral adrenal hemorrhage is an uncommon phenomenon with potential catastrophic con-sequences, such as an adrenal crisis. It has been associated with diverse entities such as sepsis, anticoagulation, malignancy, trauma, antiphospholipid syndrome and postoperative setting, among others. The diagnosis is difficult as patients present with non-specific signs and symptoms, so high suspicion should trigger imaginological test to confirm the diagnosis. We report the case of bilateral adrenal hemorrhage without adrenal insufficiency that occurred in a 71-year-old woman during her fifth postoperative day after knee osteosynthesis, who received treatment with enoxaparin as antithrombotic prophylaxis and who presented to the emergency room for 12 hours of colic-like abdominal pain accompanied by nausea without signs of hemodynamic instability.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Use of Enoxaparin in Obstetrics and Gynecology Department

Aims: This study aims to demonstrate the use of enoxaparin in obstetrics and gynecology department in Alkharj.Methodology:This is a retrospective study was conducted in a public hospital in Alkharjcity. The outpatient prescriptions were reviewed to evaluate the prescription patternsof enoxaparin. The data were collected and analyzed using Excel software, the descriptive data were represented by frequencies and percentages. Results:About 86.32% of the prescriptions contain enoxaparin syringe were prescribed for female patients. The majority of enoxaparin prescriptions were from obstetrics & gynecology department (79.48%).Moreover, the majority of enoxaparin prescriptions were prescribed by consultants (62.39%).Conclusion:The result of this study show that enoxaparin was prescribed commonly in the obstetrics and gynecology department for female patients because of its efficacy and safety profile. Enoxaparin is safer than other anticoagulants butstill could cause many adverse effects so it is important to increase the health care professional awareness about its use

Perfil de uso de anticoagulantes en pacientes hospitalizados, interacciones farmacológicas y reacciones adversas identificadas / Anticoagulant use profile in hospitalized patients, drug interactions and identified adverse reactions

RESUMEN Son conocidos los efectos de los anticoagulantes como tratamiento o profilaxis de eventos trombóticos, esto permitió establecer una terapia individualizada según sus necesidades. Se realizó un estudio descriptivo, transversal, no aleatorizado, en 138 pacientes hospitalizados mayores de edad en una institución de cuarto nivel de atención con tratamiento anticoagulante terapéutico y profiláctico, se abordó el tipo de fármaco indicado, periodicidad, efectos adversos, controles de laboratorio, interacciones farmacológicas y causalidad de las reacciones adversas. Se encontró que el anticoagulante con mayor frecuencia de uso fue enoxaparina (68%), el control más utilizado fue el tiempo de protrombina (60,39%), interacciones farmacológicas se identificaron en 47,1%, las más frecuentes con ácido acetil salicílico (29,7% del total de interacciones), las reacciones adversas más frecuentes fueron de índole hematológico (58,3%); y la evaluación de causalidad de reacciones adversas fue 4,2% probable. El estudio mostró que el anticoagulante más utilizado fue enoxaparina. Las interacciones farmacológicas de los anticoagulantes fueron muy frecuentes, especialmente con warfarina. Las reacciones adversas de mayor ocurrencia fueron las de tipo hemorrágico ; y la evaluación de causalidad fue de categoría posible para la mayoría de estas reacciones adversas.

SUMMARY The effects of anticoagulants are known as treatment or prophylaxis of thrombotic events, allowing to establish an individualized therapy according to their needs. A descriptive cross-sectional, non-randomized study was carried out in 138 hospitalized patients of legal age in a fourth-level care institution with therapeutic and prophylactic anticoagulant treatment, addressing the type of drug indicated, periodicity, side effects, laboratory controls, pharmacological interactions and causality of adverse reactions. It was found that the anticoagulant with the highest frequency of use was enoxaparin (68%), the most used control was the prothrombin time (60.39%), pharmacological interactions were identified in 47.1%, being the most frequent with acetylsalicylic acid (29.7% of the total number of interactions), the most frequent adverse reactions were of a hematological nature (58.3%); and the causality assessment of adverse reactions was 4.2% probable. The study showed that the most used anticoagulant was enoxaparin. The pharmacological interactions of anticoagulants were very frequent, especially with warfarin. The most frequent adverse reactions were those of hemorrhagic type; and the causality assessment was of possible category for most of these adverse reactions.

Comparison of empirical use of low dose aspirin and enoxaprin in the treatment of unexplained recurrent pregnancy loss

Background: Recurrent pregnancy losses have commonly been defined as three or more consecutive spontaneous pregnancy losses. About 1-2% of women suffer from recurrent miscarriages. The cause is multifactorial such as uterine anomalies, endocrine disorders, immunological causes, infections, chromosomal anomalies and maternal autoimmune diseases. In 50-60% of cases recurrent pregnancy losses, the cause remains unclear. Objective of this study was to compare the maternal and fetal outcome in patients with unexplained recurrent pregnancy loss treated with LMWH (Enoxaparin) vs Aspirin during pregnancy.Methods: Women with 3 or more pregnancy losses, aged between 18-40 years, booked for antenatal care and delivery in our hospital between January 2012 and December 2016 were followed till 6 months after delivery.Results: A total number of 146 women were assessed for eligibility. We had 62 women in Group A (aspirin group) and 84 women in Group E (enoxaparin group). Enoxaparin was given to all those ladies who had taken aspirin in previous pregnancies with no live outcome. Good neonatal outcome was observed with Enoxaparin.Conclusions: Live birth rates did not show significant difference between the two study groups. But empirical use of enoxaparin in patients with no live birth who have taken low dose aspirin in previous pregnancy had shown improved results, so enoxaparin should be used empirically as a first line agent in such cases.

Spinal anesthesia for c-section in patients with protein S deficiency: case report and literature review / Anestesia espinal para cesárea en paciente con deficiencia de proteína S: informe de caso y revisión de la literatura

Abstract Introduction: Congenital protein S deficiency is a very rare disease in the population. In pregnant women it is associated with spontaneous abortion and fetal death, among other complications. Case presentation: We present the case of a 32-year-old multigravida with a 36-week pregnancy, with thromboprophylaxis with enoxaparin from the 4th week of gestation and with a diagnosis of thrombophilia-due to functional protein S deficiency-which was intervened with elective c-section under spinal anesthesia. In addition, a review of the relevant literature was conducted. Discussion: The risk of venous thromboembolism is approximately 4 to 5 times greater during gestation, and the recommendation of thromboprophylaxis in low-risk thrombophilia is based on the presence of associated risk factors. In patients receiving low molecular weight heparin (LMWH) as thromboprophylaxis, an interval of at least 12 hours after the last dose of LMWH before neuropsy and restarting the next dose after at least 4hours of spinal technique use is recommended. Conclusion: Neuroaxial techniques should be individualized and receive pre and postpartum thromboprophylaxis. In addition, non-pharmacological thromboprophylaxis measures in the perioperative period should be considered. Spinal anesthesia was effective and safe in this patient.

Resumen Introducción: La deficiencia congénita de proteína S es una enfermedad muy rara en la población. En gestantes está asociada a aborto espontáneo y muerte fetal, entre otras complicaciones. Presentación del caso: Presentamos el caso de una multigesta de 32 años con embarazo de 36 semanas, con tromboprofilaxis con enoxaparina desde la semana cuarta de gestación y con diagnóstico de trombofilia -por deficiencia de proteína S funcional-, la cual fue intervenida con cesárea electiva bajo anestesia espinal. Además, se realizó revisión de la literatura al respecto. Discusión: El riesgo de tromboembolismo venoso es aproximadamente 4 a 5 veces mayor durante la gestación, y la recomendación de tromboprofilaxis en trombofilias de bajo riesgo se basa en la presencia de factores de riesgo asociados. En pacientes que reciben Heparinas de Bajo Peso Molecular (HBPM) como tromboprofilaxis, se recomienda un intervalo de al menos 12 horas después de la última dosis de HBPM antes de la punción del neuroeje, y reiniciar la siguiente dosis después de al menos 4 horas de uso de la técnica espinal. Conclusión: Las técnicas neuroaxiales deben ser individualizadas y recibir tromboprofilaxis pre y posparto. Además, se deben tener en cuenta las medidas de tromboprofilaxis no farmacológicas en el periodo perioperatorio. La anestesia espinal fue efectiva y segura en esta paciente.

Utilization profile of enoxaparin in hospitalized patients with Chronic Kidney Disease in southern Brazil

Chronic Kidney Disease (CKD) patients usually require the use of anticoagulants for treatment or prevention of thromboembolic diseases. One such commonly used anticoagulant is enoxaparin. However, special attention is advised when using this drug for CKD patients because dosage adjustments may be needed. This prospective observational study was conducted in adult patients (> 18 years) with CKD stages 3 to 5 who were followed-up daily via prescriptions, medical records and laboratory tests. Enoxaparin doses, renal function and adverse drug events (ADEs) were thus monitored. Of the 87 ADEs identified in this study, 56 (64.3%) occurred in patients requiring enoxaparin prescription adjustment. Out of the 9 patients who had severe ADEs, 8 (88.9%) needed enoxaparin prescription adjustment. The results of this study suggest an overall increased risk of major bleeding and ADEs in patients requiring enoxaparin prescription adjustment. Further investigation of alternative dosing regimens in patients with CKD to maintain efficacy while reducing risks is imperative, as are studies on the utility of monitoring anti-factor Xa activity to guide dosing of enoxaparin. In addition, the role of clinical pharmacists in the management of CKD patients is crucial, as dose adjustments are often necessary.

Establishment of the First National Reference Material for Low Molecular Weight Heparin / 中国药学杂志

OBJECTIVE: In June 2017, the National Pharmacopoeia Committee published on the internet the draft of national standards for dalteparin sodiumenoxaparin sodium and nadroparin calcium. As the new monographs to be added to the Chinese Pharmacopoeia in 2020. To establish the first batch national standards of low molecular weight calirantdalteparin sodiumenoxaparin sodium and nadroparin calcium for system suitability. METHODS: A national collaborative study involving thirteen laboratories had taken place, organized by National Institutes for Food and Drug Control(NIFDC)to provide supporting data for the establishment of the 1st national standards of low molecular weight heparin for molecular weight calibrantdalteparin sodium enoxaparin sodium and nadroparin calcium for system suitability of molecular weight determinations. The molecular weight determination methods in draft standards were used in the national collaborative study. The 2nd international standard low molecular weight heparin for molecular weight calibration(05/112) were used as molecular weight calibrant. The candidate national standards of low molecular weight heparin for molecular weight calibration (140820-201801) and the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination were tested in the study. RESULTS: The cumulative percent of peak area at the 18 molecular points from 600-18 000 of the candidate national standard of low molecular weight heparin for molecular weight calibration (140820-201801) were calculated. Based on the statistical analysis, the candidate gave low intra- and inter-laboratories variations.Of all 13 laboratories, standard deviations (SD) of two laboratories ranged from 1% to 2%,the others were less than 1%.Between laboratories, SD were all less than 1%,relative standard deviation(RSD) were all less than 5% except two points of the small molecular. The intra-lab SD of the test to determine the molecular weight of the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination was between 4 and 110,RSD was less than 2.5%. The inter-lab SD were less than 30, RSD was less than 1.0%. CONCLUSION: After the examination of the expert committee on pharmaceutical standardization, the candidate (140820-201801) was approved as the first national standard of low molecular weight heparin for molecular weight calibration, the broad standard table is also provided the broad standard table. The candidate(140811-201801) is approved as the first national standard of dalteparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 6 268. The candidate(140810-201801) is approved as the first national standard of enoxaparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 435. The candidate(140812-201801) was approved as the first national standard of nadroparin calcium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 832.

Effect of Modified Shoutaiwan on Recurrent Abortion Due to Prethrombotic Status and Effect on Coagulation Factors / 中国实验方剂学杂志

Objective::To observe the efficacy of modified Shoutaiwan on recurrent abortion due to prethrombotic status with kidney deficiency and blood stasis and investigate its effect on coagulation factors. Method::The 100 cases were randomly divided into control group and observation group, 50 cases in each group. Bushen Yangxue capsule + enoxaparin sodium were given in control group, while modified Shoutaiwan + enoxaparin sodium were given in observation group, with a treatment course of 60 d in both groups. The serum clotting factor activated protein S (PS), activated protein C (PC), platelet aggregation function (PAF), platelet aggregation rate (PagT), antithrombin (AT), lupus anticoagulant material positive positive predictive value (LA), anti cardiolipin antibody positive rate of positive predictive value (ACA), plasminogen activator inhibitor-1(PAI-1), tissue factor (TF), fibrinogen (Fig), fibrinogen (FIB), fibrinogen alpha granule membrane glycoprotein-140 (GMP-140), fibrinogen fragment (F1+ 2), tissue fibrinogen activation factor (t-PA), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were observed. Clinical efficacy, pregnancy rate, traditional Chinese medicine(TCM) syndromes and adverse reactions were compared between the two groups. Result::4 cases withdrew from the study. The total effective rate in observation group was 97.9% (48/49), higher than 85.1% (40/47) in control group (χ2=5.713, P<0.05). The pregnancy rate in observation group was 89.8% (44/49), higher than 70.2% (33/47) in control group (χ2=6.351, P<0.05). The score of traditional Chinese medicine syndromes in observation group was lower than that in control group. The indexes of PS, PC, AT, TF, Fig, FPA, APTT and TT in observation group were significantly higher than those in control group (P<0.05), while PAF, PagT, LA, ACA, PAI-1, PAP, TAT, FIB, GMP-140, F1+ 2, t-PA, D-D and PT were lower than those in control group (P<0.05). The incidence of adverse reactions in observation group was 10.2% (5/49), lower than 35.4% (17/48) in control group (P<0.05). Conclusion::Modified Shoutaiwan can effectively improve the clinical symptoms of recurrent abortion due to prethrombotic status and improve the coagulation factors in patients with kidney deficiency and blood stasis.

Investigation of the protective effect of enoxaparin and ticagrelor pretreatment against ischemia-reperfusion injury in rat lung tissue

SUMMARY OBJECTIVES This study was conducted to reveal the possible protective effects of ticagrelor and enoxaparin pretreatment against ischemia-reperfusion (IR)-induced injury on the lung tissue of a rat model. METHODS Wistar albino rats were randomly divided into 4 groups as follows: group-1 (control-sham), group-2 (control-saline+IR), group-3 (ticagrelor+IR), group-4 (enoxaparin+IR). Before the ischemic period, saline, ticagrelor, and enoxaparin were administered to the 2nd-4th groups, respectively. In these groups, IR injury was induced by clamping the aorta infrarenally for 2 h, followed by 4 h of reperfusion except group-1. After the rats were euthanized, the lungs were processed for histological examinations. Paraffin sections were stained with Haematoxylin&Eosin (H&E) for light microscopic observation. Apoptosis was evaluated by caspase-3 immunoreactivity. Data were statistically analyzed using the SPSS software. RESULTS In the lung sections stained with H&E, a normal histological structure was observed in group-1, whereas disorganized epithelial cells, hemorrhage, and inflammatory cell infiltration were seen in the alveolar wall in group-2. The histologic structure of the treatment groups was better than that of group-2. Caspase-3(+) apoptotic cells were noticeable in sections of group-2 and were lower in the treatment groups. In group-4, caspase-3 immunostaining was lower than in group-3. In group-2, apoptotic cells were significantly higher than in the other groups (p<0.001). CONCLUSION Based on the histological results, we suggested that both therapies ameliorated the detrimental effects of IR. Caspase-3 immunohistochemistry results also revealed that pre-treatment with enoxaparin gave better results in an IR-induced rat injury model. In further studies, other parameters such as ROS and inflammatory gene expressions should be evaluated for accurate results.

RESUMO OBJETIVOS Este estudo foi realizado para revelar os possíveis efeitos protetores do ticagrelor e do pré-tratamento da enoxaparina no tecido pulmonar contra o modelo de lesão induzida por isquemia-reperfusão (IR). MÉTODOS Ratos albinos Wistar foram randomizados e divididos em quatro grupos: grupo 1 (controle-sham), grupo 2 (controle-salina + IR), grupo 3 (ticagrelor + IR), grupo 4 (enoxaparina + IR). Antes do período isquêmico, salina, ticagrelor e enoxaparina foram administrados nos grupos 2-4, respectivamente. Nesses grupos, a lesão de IR foi induzida pelo clampeamento da aorta na região da infrarrenal por duas horas, seguida por quatro horas de reperfusão, exceto no grupo 1. Após a sacrificação, os pulmões foram processados para exames histológicos. Secções de parafina foram coradas com hematoxilina e eosina (H&E) para observação microscópica de luz. A apoptose foi avaliada pela imunorreatividade da caspase-3. Os dados foram analisados estatisticamente pelo programa SPSS. RESULTADOS Nas secções pulmonares coradas com H&E, estrutura histológica normal foi observada no grupo 1, enquanto células epiteliais desorganizadas, hemorragia e infiltração de células inflamatórias foram observadas na parede alveolar no grupo 2. A estrutura histológica dos grupos de tratamento foi melhor que o grupo 2. Células apoptóticas caspase-3 (+) foram notadas em secções do grupo 2, e essas células foram mais baixas nos grupos de tratamento. No grupo 4, a imunocoloração com caspase-3 foi menor que no grupo 3. No grupo 2, as células apoptóticas foram significativamente maiores que nos outros grupos (p<0,001). CONCLUSÃO Com base nos resultados histológicos, sugerimos que ambas as terapias atenuaram os efeitos prejudiciais da RI. Resultados de imuno-histoquímica com caspase-3 também revelaram que o pré-tratamento com enoxaparina proporcionou melhores resultados no modelo de lesão induzida por IR. Em estudos posteriores, outros parâmetros, como ROS e expressões gênicas inflamatórias, devem ser avaliados quanto a resultados precisos.

Revisão sistemática da profilaxia para tromboembolismo venoso após artroplastia do joelho: enoxaparina versus rivaroxabana / Systematic review of prophylaxis for venous thromboembolism after knee arthroplasty: enoxaparin versus rivaroxaban

RESUMO A artroplastia total do joelho é um procedimento eletivo, realizado em indivíduos relativamente saudáveis. Porém, devido ao risco inerente de tromboembolismo venoso, são utilizados fármacos para sua profilaxia. O objetivo do presente trabalho foi conduzir uma revisão sistemática da literatura para comparar a eficácia da enoxaparina e da rivaroxabana na prevenção desta complicação e no risco de sangramento intraoperatório. Foi feita uma revisão no site SciELO, Pubmed e Cochrane através dos descritores, artroplastia de joelho, rivaroxabana e enoxaparina através da estratégia de busca PICO. Os critérios de inclusão foram os artigos no período estudado, que comparavam ambas as drogas em cirurgias de artroplastia do joelho. Os critérios de relevância para tornar o estudo elegível foram definidos como: somente artigos publicados a partir 2010 e com casuística com mais de 20 pacientes foram considerados; somente estudos obtidos em sua íntegra foram analisados; somente estudos com seguimento maior do que 12 meses foram considerados relevantes. As variáveis utilizadas para a comparação dos artigos foram as complicações mais comuns no pós-operatório de artroplastias do joelho: tromboembolismo venoso e sangramento. Foi utilizado o Review Man 5.3 para estruturação da revisão. Os autores observaram que nos estudos analisados, considerando tromboembolismo venoso sintomático, a rivaroxabana resultou em maiores benefícios quando comparada com a enoxaparina.

ABSTRACT Total knee arthroplasty is an elective procedure performed on relatively healthy individuals. However, due to the inherent risk of venous thromboembolism, drugs are used for its prophylaxis. The objective of the present study was to conduct a systematic review of the literature to compare the efficacy of enoxaparin and rivaroxaban in preventing this complication and the risk of intraoperative bleeding. We reviewed the SciELO, Pubmed and Cochrane databases with the descriptors knee arthroplasty, rivaroxaban and enoxaparin through the PICO search strategy. Inclusion criteria were the articles during the study period comparing both drugs in knee arthroplasty. Relevant criteria to study eligibility were articles published since 2010 and with a sample of more than 20 patients; studies obtained in their entirety; and studies with follow-up of more than 12 months. The variables used to compare the articles were the most common postoperative complications of knee arthroplasties: venous thromboembolism and bleeding. We used the Review Man software, version 5.3, for structuring the review. In the studies analyzed, considering symptomatic venous thromboembolism, rivaroxaban resulted in higher benefits when compared to enoxaparin.

Sobredosis accidental de enoxaparina en un recién nacido / Enoxaparin overdose in a newborn

La enoxaparina es una heparina de bajo peso molecular utilizada en el período neonatal. Requiere menor monitoreo que la heparina estándar o no fraccionada, si bien es escaso el conocimiento actual acerca de su dosis y de los niveles terapéuticos en los neonatos. Además, existe una información muy limitada respecto del manejo de su sobredosificación en este grupo de edad. Se presenta el primer caso publicado en castellano de un neonato que recibió una dosis de enoxaparina diez veces superior a la terapéutica de forma accidental y en el que se administró una dosis aislada de protamina para revertir su efecto.

Enoxaparin is a low molecular weight heparin used in the neonatal period. It requires less monitoring than standard or unfractionated heparin, although current knowledge about its dose and therapeutic levels in neonates is scarce. In addition, there is very limited information about the management of overdose in this age group. We present the first case published in Spanish of a neonate who accidentally received a dose of enoxaparin ten times higher than the therapeutic one and an isolated dose of protamine to reverse its effect.