BACKGROUND Factor XI(FXI)deficiency,also known as hemophilia C,is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity.This often poses great challenges in perioperat...BACKGROUND Factor XI(FXI)deficiency,also known as hemophilia C,is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity.This often poses great challenges in perioperative hemostatic management.Thromboelastography(TEG)is a method for testing blood coagulation using a viscoelastic hemostatic assay of whole blood to assess the overall coagulation status.Here,we present the successful application of intraoperative TEG monitoring in an FXI-deficient patient as an individualized blood transfusion strategy.CASE SUMMARY A 21-year-old male patient with FXI deficiency was scheduled to undergo reconstructive surgery for macrodactyly of the left foot under general anesthesia.To minimize his bleeding risk,he was scheduled to receive fresh frozen plasma(FFP)as an empirical prophylactic FXI replacement at a dose of 15-20 mL/kg body weight(900-1200 mL)before surgery.Subsequent FFP transfusion was to be adjusted according to surgical need.Instead,TEG assessment was used at the beginning and toward the end of his surgery.According to intraoperative TEG results,the normalization of coagulation function was achieved with an infusion of only 800 mL FFP,and blood loss was minimal.The patient showed an uneventful postoperative course and was discharged on postoperative day 8.CONCLUSION TEG can be readily applied in the intraoperative period to individualize transfusion needs in patients with rare inherited coagulopathy.展开更多
Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a...Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a new mutant form of FXIa catalytic domain rhFXI370-607 （N73Q-N113Q-C123S）, and report here the facile preparation, protein crystallization, and crystal structure of this protein. We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels. This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.展开更多
BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability...BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability of DVT are not fully understood.AIM To evaluate the relationships between plasma antigen levels of factor XII(FXII:Ag)and factor XI(FXI:Ag)with the stability of DVT.METHODS Patients with DVT and no PE,DVT and PE,and controls with no DVT or PE that matched for age,gender,and comorbidities were included in this study.FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.RESULTS Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off,a higher FXI:Ag was associated with a higher risk of unstable DVT(odds ratio:3.15,95%confidence interval:1.18-8.43,P=0.019).Stratified analyses showed consistent results in patients≤60 years(P=0.020),but not in those>60 years(P=0.346).CONCLUSION Higher plasma FXI:Ag might be a marker for unstable DVT,which might be associated with PE in these patients.展开更多
Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threa...Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threatening disseminated intravascular coagulation ( DIC),and deep venous thromboembolism (DVT) and pulmonary embolism.Antithrombosis encompasses several aspects:coagulation,platelets,fibrinolysis,vascular endothelial cells,hemodynamics and hemorheology.Among them,anticoagulation is a fundamental step in antithrombotic therapy.Existing anticoagulants inhibit coagulation factors effectively,and are countered by substantial limitations with severe bleeding risk.For newer generation anticoagulant development,it is important to achieve a low ratio of hemorrhagic risk/antithrombotic benefit.展开更多
凝血因子XI缺陷症(Factor XI deficiency)是荷斯坦牛的一种常染色体单基因控制的隐性遗传缺陷。该病的遗传基础是由位于牛第27号染色体的凝血因子XI基因外显子12上发生的一段76bp序列插入。本研究采用PCR方法对我国13个主要公牛站的571...凝血因子XI缺陷症(Factor XI deficiency)是荷斯坦牛的一种常染色体单基因控制的隐性遗传缺陷。该病的遗传基础是由位于牛第27号染色体的凝血因子XI基因外显子12上发生的一段76bp序列插入。本研究采用PCR方法对我国13个主要公牛站的571头荷斯坦公牛的凝血因子XI基因进行了全面检测,未发现隐性有害基因携带者和纯合个体。展开更多
基金Education Reform Project Foundation for the Central Universities of Peking Union Medical College,No.2020zlgc0105Training Programme Foundation for Excellent Talent in Dongcheng District of Beijing,No.2019DCTM-08Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2019XK320018.
文摘BACKGROUND Factor XI(FXI)deficiency,also known as hemophilia C,is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity.This often poses great challenges in perioperative hemostatic management.Thromboelastography(TEG)is a method for testing blood coagulation using a viscoelastic hemostatic assay of whole blood to assess the overall coagulation status.Here,we present the successful application of intraoperative TEG monitoring in an FXI-deficient patient as an individualized blood transfusion strategy.CASE SUMMARY A 21-year-old male patient with FXI deficiency was scheduled to undergo reconstructive surgery for macrodactyly of the left foot under general anesthesia.To minimize his bleeding risk,he was scheduled to receive fresh frozen plasma(FFP)as an empirical prophylactic FXI replacement at a dose of 15-20 mL/kg body weight(900-1200 mL)before surgery.Subsequent FFP transfusion was to be adjusted according to surgical need.Instead,TEG assessment was used at the beginning and toward the end of his surgery.According to intraoperative TEG results,the normalization of coagulation function was achieved with an infusion of only 800 mL FFP,and blood loss was minimal.The patient showed an uneventful postoperative course and was discharged on postoperative day 8.CONCLUSION TEG can be readily applied in the intraoperative period to individualize transfusion needs in patients with rare inherited coagulopathy.
基金Supported by FJIRSM (SZD08003)the National Natural Science Foundation of China(30811130467,30625011,30770429)Chinese Academy of Sciences (KSCX2-YW-R-082)
文摘Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a new mutant form of FXIa catalytic domain rhFXI370-607 （N73Q-N113Q-C123S）, and report here the facile preparation, protein crystallization, and crystal structure of this protein. We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels. This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.
基金Supported by the Fund for Key Research and Development Program Project of Shannxi ProvinceNo. 2017SF-254
文摘BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability of DVT are not fully understood.AIM To evaluate the relationships between plasma antigen levels of factor XII(FXII:Ag)and factor XI(FXI:Ag)with the stability of DVT.METHODS Patients with DVT and no PE,DVT and PE,and controls with no DVT or PE that matched for age,gender,and comorbidities were included in this study.FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.RESULTS Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off,a higher FXI:Ag was associated with a higher risk of unstable DVT(odds ratio:3.15,95%confidence interval:1.18-8.43,P=0.019).Stratified analyses showed consistent results in patients≤60 years(P=0.020),but not in those>60 years(P=0.346).CONCLUSION Higher plasma FXI:Ag might be a marker for unstable DVT,which might be associated with PE in these patients.
文摘Introduction Thrombosis is a major pathological process that threatens human health.It underlies the pathogenesis of the leading causes of death myocardial infarction (MI)and ischemic stroke (IS),as well as life-threatening disseminated intravascular coagulation ( DIC),and deep venous thromboembolism (DVT) and pulmonary embolism.Antithrombosis encompasses several aspects:coagulation,platelets,fibrinolysis,vascular endothelial cells,hemodynamics and hemorheology.Among them,anticoagulation is a fundamental step in antithrombotic therapy.Existing anticoagulants inhibit coagulation factors effectively,and are countered by substantial limitations with severe bleeding risk.For newer generation anticoagulant development,it is important to achieve a low ratio of hemorrhagic risk/antithrombotic benefit.
文摘凝血因子XI缺陷症(Factor XI deficiency)是荷斯坦牛的一种常染色体单基因控制的隐性遗传缺陷。该病的遗传基础是由位于牛第27号染色体的凝血因子XI基因外显子12上发生的一段76bp序列插入。本研究采用PCR方法对我国13个主要公牛站的571头荷斯坦公牛的凝血因子XI基因进行了全面检测,未发现隐性有害基因携带者和纯合个体。
