Randomized Trial of Deep Vein Thrombosis Chemoprophylaxis with Bemiparin and Enoxaparin in Patients with Moderate to High Thrombogenic Risk Undergoing Plastic and Reconstructive Surgery Procedures.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication during postoperative convalescence characterized by hypercoagulability, vascular endothelium damage and blood stasis. It increases noticeably in peri/postoperative phases of surgery procedures. Pulmonary embolism secondary to iliofemoral DVT is a frequent cause of death. METHODS: Adult patients scheduled for plastic and reconstructive surgery (PRSx) with moderate to high thrombogenic risk were selected. We evaluated the efficacy and safety of bemiparin compared to enoxaparin as chemoprophylaxis for DVT. Following balanced general anesthesia techniques, patients were randomly assigned for subcutaneous enoxaparin 40 IU (Group-E) or bemiparin 3500 IU (Group-B) q24h starting 6 h after procedure conclusion for at least 10 days. All patients were evaluated for DVT through Doppler ultrasound mapping of the lower limbs. RESULTS: Seventy-eight patients were evaluated, mostly women (83%), physical status ASA II (59%), ASA III (10%); Caprini's thrombogenic risk score 3-4 (moderate) 58%, 5-6 (high) 29%, > 6 (too high) 13%; demographics, clinical variables and scores were similar between groups. Median drainage time in breast surgery was 4 days in both groups (p = 0.238). In the case of abdominal surgery, median was 14 days in Group-E versus 13 days in Group-B (p = 0.059). No DVT was detected in either group. CONCLUSIONS: DVT was prevented with bemiparin, without significant bleeding increase nor adverse events; moreover, the cost of bemiparin is lower than enoxaparin. Bemiparin can be considered as alternative drug for DVT chemoprophylaxis in PRSx procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Monitoring anti-Xa levels in patients with cancer-associated venous thromboembolism treated with bemiparin.

OBJECTIVE: To analyze the relationship between therapeutic (weight-adjusted) dose of bemiparin and anti-Xa activity in patients with venous thromboembolism (VTE) and cancer in comparison with a cohort of patients with VTE without cancer, and its relationship with outcomes. MATERIALS AND METHODS: This is a prospective cohort study that comprised a cohort of patients with cancer-associated VTE and a cohort of non-cancer patients with VTE, all of them treated with bemiparin. The ethics committee approved the study and informed consent was obtained from the patients. RESULTS: One hundred patients were included (52 with cancer and 48 without cancer), with a median follow-up of 9.8 months. Mean anti-Xa activity was 0.89 (± 0.33) UI/mL in oncological patients and 0.83 (± 0.30) UI/mL in non-cancer patients (mean difference - 0.05 95% CI - 0.18; 0.06). A multiple linear regression model showed that anti-Xa peak was associated with the dose/kg independently of possible confounding variables (presence of cancer, age, sex and eGFR-estimated Glomerular Filtration Rate), in a way that for every 1 UI of dose/kg increase, the anti-Xa peak activity increased 0.006 UI/mL (95% CI 0.003; 0.009) (p < 0.001). The predictive capacity of anti-Xa peak in the oncology cohort showed an area under the ROC curve of 0.46 (95% CI 0.24-0.68), 0.70 (95% CI 0.49-0.91) and 0.74 (95% CI 0.44-0.94) for death, first bleeding and recurrence of VTE, respectively, and none was statistically significant. CONCLUSION: In patients with venous thromboembolism treated with bemiparin, anti-Xa levels were not influenced by the presence of cancer.

Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study.

INTRODUCTION: Low-molecular-weight heparin (LMWH) is the standard treatment for cancer-associated venous thromboembolism (VTE). There have been no specific studies evaluating bemiparin for VTE in people with cancer. The aim of this study is to evaluate the effects of bemiparin for long-term treatment of VTE in routine clinical practice. METHODS/PATIENTS: Prospective observational study. Consecutive patients with active cancer and VTE, under treatment with bemiparin for at least 6 months, were recruited. RESULTS: We included 89 patients. The 6- and 9-month cumulative VTE recurrence rates were 2.4% and 5.9%, respectively. The 6-month cumulative rate of major bleeding was 1.3%, and of clinically relevant non-major bleeding, 8%. CONCLUSIONS: The incidence of events in this study is lower than that reported in randomized trials. Bemiparin is effective and safe for the long-term treatment of cancer-associated VTE in routine clinical practice.

Perfil de seguridad de bemiparina como tromboprofilaxis en pacientes crítico / Safety profile of bemiparin thromboprofilaxis in critically III patients / Perfil de segurança da bemiparina como tromboprofilaxia em pacientes en estado crítico

Resumen: Introducción: La enfermedad tromboembólica es una causa prevenible de mortalidad en pacientes críticamente enfermos. La estrategia de tromboprofilaxis más utilizada es el uso de heparinas de bajo peso molecular; sin embargo, no se conoce cuál es superior. La bemiparina presenta características farmacológicas favorables. Objetivo: Evaluar el perfil de seguridad de la tromboprofilaxis con bemiparina en pacientes críticos. Material y métodos: Se trata de un estudio retrospectivo y observacional. Se incluyeron pacientes hospitalizados en la Unidad de Cuidados Intensivos de Adultos entre diciembre de 2013 y junio de 2015 que recibieron bemiparina. Se evaluó la presencia de sangrado mayor, trombocitopenia y correlaciones entre la dosis administrada y la presencia de eventos adversos. Resultados: 111 pacientes críticos recibieron bemiparina como tromboprofilaxis. No hubo episodios de enfermedad tromboembólica. Seis punto tres por ciento de los pacientes presentaron sangrado mayor durante su estancia. La incidencia de trombocitopenia severa fue de 1.8%, 8.6% presentó descenso en la cuenta plaquetaria sugerente de trombocitopenia inducida por heparina; no obstante, no se documentó ningún caso. Los efectos adversos no se asociaron a mayores dosis de bemiparina. Conclusiones: La seguridad de la tromboprofilaxis con bemiparina es comparable con el resto de las heparinas de bajo peso molecular (HBPM) en pacientes críticamente enfermos.

Abstract: Introduction: Venous thromboembolism is a preventable cause of death in critically ill patients. The most common thromboprophylaxis strategy is the use of low molecular weight heparins, however it is not known which is superior. Bemiparin shows a favorable pharmacologic profile. Objective: Evaluate the safety profile of bemiparin thromboprophylaxis in the critically ill. Materials and methods: This retrospective observational trail was carried out in an adult intensive care unit. Patients hospitalized between December 2013 and June 2015 receiving bemiparin throboprophylaxis were included. The presence of major bleeding, thrombocytopenia and the correlation between dose and adverse events was noted. Results: 111 critically ill patients received bemiparin thromboprophylaxis No episodes of venous thromboembolism were recorded. 6.3% of patients had a major bleeding episode during their intensive care unit stay. The incidence of severe thrombocytopenia was 1.8%, while 8.6% of patients had a platelet count decrease typical of heparin induced thrombocytopenia, no cases were recorded. Adverse events were not associated with bemiparin dose. Conclusions: The safety of bemiparin thromboprofilaxis is similar to that of other Low Molecular Weight Heparins (LMWH) in critically ill patients.

Resumo: Antecedentes: A doença tromboembólica é uma causa evitável de morte em pacientes em estado crítico. A estratégia tromboprofiláxica mais utilizada é o uso de heparinas de baixo peso molecular, no entanto, não é conhecido qual é superior. A bemiparina apresenta características farmacológicas favoráveis. Objetivo: Avaliar o perfil de segurança da tromboprofilaxia com bemiparina em pacientes em estado crítico. Material e métodos: Estudo retrospectivo observacional na unidade de terapia intensiva de adultos. Foram incluídos pacientes hospitalizados na unidade de terapia intensiva que receberam bemiparina entre dezembro de 2013 e junho 2015. Avaliou-se a presença de hemorragia grave, trombocitopenia e correlações entre doses administrada e a presença de eventos adversos. Resultados: 111 pacientes em estado crítico receberam bemiparina como tromboprofilaxia. Não houve episódios de tromboembolismo. 6.3% dos pacientes apresentaram sangramento maior durante a sua estadia. A incidência de trombocitopenia grave foi de 1.8%, 8.6% apresentaram uma diminuição na contagem de plaquetas sugestivos de trombocitopenia induzida pela heparina, porém não se documentou nenhum caso. Os efeitos adversos não se associaram com a doses mais elevadas de bemiparina. Conclusão: A segurança de tromboprofilaxia bemiparina é comparável com o resto do Heparina de baixo peso molecular (HBPM) em pacientes em estado critico.

Thermosensitive macroporous cryogels functionalized with bioactive chitosan/bemiparin nanoparticles.

Thermosensitive macroporous scaffolds of poly(N-isopropylacrylamide) (polyNIPA) loaded with chitosan/bemiparin nanoparticles are prepared by the free radical polymerization in cryogenic conditions. Chitosan/bemiparin nanoparticles of 102 ± 6.5 nm diameter are prepared by complex coacervation and loaded into polyNIPA cryogels. SEM image reveal the highly porous structure of cryogels and the integration of nanoparticles into the macroporous system. Volume phase transition temperature (VPT) and total freezing water content of cryogels are established by differential scanning calorimetry, and their porosity is determined by image-NMR. Swelling of cryogels (above and below the VPT) is highly dependent on nanoparticles concentration. In vitro release profile of bemiparin from cryogel is highly modulated by the presence of chitosan. Bemiparin released from nanoparticles preserves its biological activity, as shown by the BaF32 cell proliferation assay. Cryogels are not cytotoxic for the human fibroblast cells and present excellent properties for application on tissue engineering and controlled release of heparin.