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OBJECTIVE: To verify whether low-molecular-weight heparin (LMWH) could increase pregnancy rates and/or decrease abortion rates in women with thrombophilia undergoing assisted reproduction cycles. METHODS: Cross-sectional study with patients undergoing in vitro fertilization (IVF) (N = 104). Women without thrombophilia (control group, n = 20), women with thrombophilia who did not receive LMWH (untreated group, n = 30), and women with thrombophilia, treated with daily enoxaparin from the day of embryo transfer until week 36 of gestation (treated group, n = 54). All women underwent controlled ovarian hyperstimulation. IVF was performed by intracytoplasmic sperm injection, and embryos were transferred on day 3. Pregnancy was detected by ß-human chorionic gonadotropin (biochemical pregnancy) and fetal heartbeat at week 5 to 6. Ongoing pregnancy was determined by ultrasound on week 12. RESULTS: Patients in the untreated thrombophilia group presented with significantly lower ongoing pregnancy rates and live birth rates and significantly higher early pregnancy loss and abortion rates when compared with the control and the treated thrombophilia groups. CONCLUSIONS: In women with diagnosed coagulation disorders, use of LMWH is important to avoid miscarriages.

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BACKGROUND: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE. RESEARCH DESIGN AND METHODS: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis. RESULTS: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) (p = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) (p = 0.64). CONCLUSIONS: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

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BACKGROUND: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI therapy, the effects of ENOX on the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by cardiac ischemia and reperfusion (CIR) were evaluated, with or without ADO signaling blockers. METHODS: To induce CIR, adult male Wistar rats were anesthetized and subjected to CIR. Electrocardiogram (ECG) analysis was used to evaluate CIR-induced VA, AVB, and LET incidence, after treatment with ENOX. ENOX effects were evaluated in the absence or presence of an ADO A1-receptor antagonist (DPCPX) and/or an inhibitor of ABC transporter-mediated cAMP efflux (probenecid, PROB). RESULTS: VA incidence was similar between ENOX-treated (66%) and control rats (83%), but AVB (from 83% to 33%) and LET (from 75% to 25%) incidences were significantly lower in rats treated with ENOX. These cardioprotective effects were blocked by either PROB or DPCPX. CONCLUSION: These results indicate that ENOX was effective in preventing severe and lethal arrhythmias induced by CIR due to pharmacological modulation of ADO signaling in cardiac cells, suggesting that this cardioprotective strategy could be promising in AMI therapy.

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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.

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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

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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.

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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.

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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.

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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.

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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.

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