One disadvantage of direct anticoagulant drug is the lack of an antidote, which may become relevant in patients with traumatic brain in- jury. A 77-years old man with atrial fibrillation and syncope received dabigatra...One disadvantage of direct anticoagulant drug is the lack of an antidote, which may become relevant in patients with traumatic brain in- jury. A 77-years old man with atrial fibrillation and syncope received dabigatran despite recurrent falls. Due to a ground-level-fall, he suffered from subarachnoidal and intraparenchymal hemorrhages, subdural hematoma and brain edema with a midline shift. Despite osteoelast/c trepanation and hematoma-evacuation he remained comatose and died seven days later without regaining consciousness. Most probably, decreased dabigatran clearance due to increased age might have contributed to the fatal course. We suggest withholding anticoagulant therapy in patients with unexplained falls. If anticoagulant therapy is deemed necessary, vitamin-K-antagonists with their potential for laboratory monitoring and reversal of anticoagulant activity should be preferred.展开更多
Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI...Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking dabigatran.Methods A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were analyzed.The exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,respectively.Cox proportional hazards regression analysis was used to evaluate the association between BMI and the risk of bleeding.Moreover,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was conducted.Results During the six-month follow-up,50 participants experienced bleeding.Every 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(<22.5 kg/m^2),the adjusted hazard ratio(HR)of bleeding for participants in Tertile 2(22.5–25.3 kg/m^2)and Tertile 3(>25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),respectively.The Ptrend-value was significant in all models.The adjusted smooth curve showed a linear association between BMI and bleeding.None of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.展开更多
Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring.Yet,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially ...Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring.Yet,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised recently.The aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very elderly.Methods Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective cohort.Prescriptions were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).Conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.展开更多
目的观察常规凝血试验结果与血浆达比加群浓度的相关性,寻找合适的试验用于监测达比加群服药患者的出血风险。方法分析北京大学第三医院2015年至2017年使用达比加群抗凝的49名非瓣膜性心房颤动(NVAF)患者的临床资料,并计算其出血发生率...目的观察常规凝血试验结果与血浆达比加群浓度的相关性,寻找合适的试验用于监测达比加群服药患者的出血风险。方法分析北京大学第三医院2015年至2017年使用达比加群抗凝的49名非瓣膜性心房颤动(NVAF)患者的临床资料,并计算其出血发生率。收集20名健康志愿者的血浆,制成正常混合血浆(NPP),分别向1 m L NPP中加入0~1 000 ng/m L浓度梯度的达比加群,检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)和稀释蝰蛇毒时间(dRVVT)。另外收集3名健康志愿者的新鲜全血,做相同的加药处理后进行血栓弹力图试验(TEG)。结果服用达比加群的NVAF患者的出血发生率高达28.6%,以消化道出血居多。APTT、dRVVT、TEG的R时间(R)和凝血指数(CI)结果与血浆达比加群浓度相关性良好,其中,dRVVT的敏感性最强,APTT次之,R和CI敏感性较差。结论 APTT和dRVVT在监测达比加群出血事件方面具有重要意义,将有助于临床寻找合适的停药时机,减少出血事件的发生。展开更多
文摘One disadvantage of direct anticoagulant drug is the lack of an antidote, which may become relevant in patients with traumatic brain in- jury. A 77-years old man with atrial fibrillation and syncope received dabigatran despite recurrent falls. Due to a ground-level-fall, he suffered from subarachnoidal and intraparenchymal hemorrhages, subdural hematoma and brain edema with a midline shift. Despite osteoelast/c trepanation and hematoma-evacuation he remained comatose and died seven days later without regaining consciousness. Most probably, decreased dabigatran clearance due to increased age might have contributed to the fatal course. We suggest withholding anticoagulant therapy in patients with unexplained falls. If anticoagulant therapy is deemed necessary, vitamin-K-antagonists with their potential for laboratory monitoring and reversal of anticoagulant activity should be preferred.
基金supported by the Major New Drug Creation Program from National Science and Technology Major Project of China(2014ZX09303305).
文摘Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking dabigatran.Methods A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were analyzed.The exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,respectively.Cox proportional hazards regression analysis was used to evaluate the association between BMI and the risk of bleeding.Moreover,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was conducted.Results During the six-month follow-up,50 participants experienced bleeding.Every 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(<22.5 kg/m^2),the adjusted hazard ratio(HR)of bleeding for participants in Tertile 2(22.5–25.3 kg/m^2)and Tertile 3(>25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),respectively.The Ptrend-value was significant in all models.The adjusted smooth curve showed a linear association between BMI and bleeding.None of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.
文摘Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring.Yet,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised recently.The aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very elderly.Methods Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective cohort.Prescriptions were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).Conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.
文摘目的观察常规凝血试验结果与血浆达比加群浓度的相关性,寻找合适的试验用于监测达比加群服药患者的出血风险。方法分析北京大学第三医院2015年至2017年使用达比加群抗凝的49名非瓣膜性心房颤动(NVAF)患者的临床资料,并计算其出血发生率。收集20名健康志愿者的血浆,制成正常混合血浆(NPP),分别向1 m L NPP中加入0~1 000 ng/m L浓度梯度的达比加群,检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)和稀释蝰蛇毒时间(dRVVT)。另外收集3名健康志愿者的新鲜全血,做相同的加药处理后进行血栓弹力图试验(TEG)。结果服用达比加群的NVAF患者的出血发生率高达28.6%,以消化道出血居多。APTT、dRVVT、TEG的R时间(R)和凝血指数(CI)结果与血浆达比加群浓度相关性良好,其中,dRVVT的敏感性最强,APTT次之,R和CI敏感性较差。结论 APTT和dRVVT在监测达比加群出血事件方面具有重要意义,将有助于临床寻找合适的停药时机,减少出血事件的发生。
