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Xiaohui Qi - One of the best experts on this subject based on the ideXlab platform.

  • chemical characteristic of an anticoagulant active sulfated polysaccharide from enteromorpha clathrata
    Carbohydrate Polymers, 2012
    Co-Authors: Xiaohui Qi, Yin Chen, Yanli Chen, Chunqi Zhao, Na Li, Chunyan Wang, Jimiao Shan
    Abstract:

    Abstract A sulfated polysaccharide FEP from marine green alga Enteromorpha clathrata was extracted with hot water and further purified by ion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that FEP was a high arabinose-containing sulfated polysaccharide with sulfate ester of 31.0%, and its average molecular weight was about 511 kDa. The backbone of FEP was mainly composed of (1 → 4)-linked β- l -arabinopyranose residues with partially sulfate groups at the C-3 position. In vitro anticoagulant assay indicated that FEP effectively prolonged the activated partial thromboplastin Time and Thrombin Time. The investigation demonstrated that FEP was a novel sulfated polysaccharide with different chemical characteristics from other sulfated polysaccharides from marine algae, and could be a potential source of anticoagulant.

  • chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from monostroma latissimum chlorophyta
    International Journal of Biological Macromolecules, 2009
    Co-Authors: Hongyan Li, Huijuan Zhang, Yi Li, Xiaohui Qi
    Abstract:

    A polysaccharide was isolated from marine green algae Monostroma latissimum, and its chemical characteristic and anticoagulant activity were investigated. The results demonstrated that the polysaccharide was high rhamnose-containing sulfated polysaccharide, and was mainly composed of 1,2-linked l-rhamnose residues with sulfate groups substituted at positions C-3 and/or C-4. The sulfated polysaccharide exhibited high anticoagulant activities by assays of the activated partial thromboplastin Time (APTT) and Thrombin Time (TT). The anticoagulant property of the sulfated polysaccharide was mainly attributed to powerful potentiation Thrombin by heparin cofactor II.

  • heparinoid active two sulfated polysaccharides isolated from marine green algae monostroma nitidum
    Carbohydrate Polymers, 2008
    Co-Authors: Fang Fang, Hongyan Li, Xiaohui Qi
    Abstract:

    Two sulfated polysaccharides WF1 and WF3 were isolated from marine green algae Monostroma nitidum, and their structural characteristics were determined. Anticoagulant activities of WF1 and WF3 were evaluated by assays of the activated partial thromboplastin Time (APTT), Thrombin Time (TT), proThrombin Time (PT), antiThrombin and anticoagulation factor Xa activities. The results showed that WF1 and WF3 had similar high contents of rhamnose, whereas their sulfate contents, sulfation positions, molecular sizes and linkage patterns of rhamnose residues were different. The bioassay results demonstrated that WF1 and WF3 had high anticoagulant activities, and were potent Thrombin inhibitors mediated by heparin cofactor II, especially WF3. They also hastened Thrombin and coagulation factor Xa inhibition by potentiating antiThrombin III, but at a lower effectiveness. The differences of anticoagulant activities between WF1 and WF3 were directly due to their structural features discrepancy.

Elaine M Hylek - One of the best experts on this subject based on the ideXlab platform.

  • idarucizumab for dabigatran reversal full cohort analysis
    The New England Journal of Medicine, 2017
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Joanne Van Ryn
    Abstract:

    BackgroundIdarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. MethodsWe performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted Thrombin Time or ecarin clotting Time. Secondary end points included the restoration of hemostasis and safety measures. ResultsA total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted Thrombin Time or the ecarin clotting Time. In group A, 137 patients (45.5%) presented ...

  • Idarucizumab for Dabigatran Reversal
    The New England journal of medicine, 2015
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Peter Verhamme, Pieter W. Kamphuisen
    Abstract:

    BACKGROUND Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran. METHODS We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute Thrombin Time or ecarin clotting Time. A key secondary end point was the restoration of hemostasis. RESULTS This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute Thrombin Time and 81 with an elevated ecarin clotting Time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated. CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.)

John W Eikelboom - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the ecarin chromogenic assay and diluted Thrombin Time for quantification of dabigatran concentrations
    Journal of Thrombosis and Haemostasis, 2017
    Co-Authors: Iqbal H Jaffer, Noel C. Chan, John W Eikelboom, James C Fredenburgh, Robin S. Roberts, Jeffrey I Weitz
    Abstract:

    Essentials Routine monitoring is unnecessary but measuring dabigatran levels is helpful in certain situations. We compared ecarin chromogenic assay (STA-ECA-II) and dilute Thrombin Time (dTT) in patient samples. Both tests provided accurate measurements over a wide range of dabigatran concentrations. Adoption of STA-ECA-II and dTT into routine clinical practice will improve patient care. SummaryBackground Although routine coagulation monitoring is unnecessary, measuring plasma dabigatran concentrations can be useful for detecting drug accumulation in renal failure or overdose, assessing the contribution of dabigatran to serious bleeding, planning the timing of urgent surgery or intervention, or determining the suitability for thrombolytic therapy for acute ischemic stroke. Dabigatran concentrations can be quantified using chromogenic or clot-based tests, such as the ecarin chromogenic assay (ECA) and the diluted Thrombin Time (dTT), respectively. Objective The purpose of this study was to compare the results of these assays with dabigatran concentrations measured by the reference standard of mass spectrometry in samples from 50 dabigatran-treated patients collected at peak and trough after at least 4 months of drug intake. Methods Drug levels measured with either the STA Ecarin Chromogenic Assay-II (STA-ECA-II) or dTT were linearly correlated with those determined by mass spectrometry over a wide range of concentrations. Results and Conclusions For detection of levels below 50 ng mL−1 both tests have specificities of at least 96%, suggesting that they accurately detect even low levels of drug. Therefore, regardless of whether a chromogenic or clot-based platform is preferred, the STA-ECA-II and dTT are useful tests for measuring dabigatran concentrations. Unfortunately, neither test is licensed by the United States Food and Drug Administration. Although approved in other jurisdictions, the dTT and STA-ECA-II are not widely or rapidly available in most hospitals. Therefore, cooperation between regulators and hospitals is urgently needed to render these tests readily available to inform patient care.

  • idarucizumab for dabigatran reversal full cohort analysis
    The New England Journal of Medicine, 2017
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Joanne Van Ryn
    Abstract:

    BackgroundIdarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. MethodsWe performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted Thrombin Time or ecarin clotting Time. Secondary end points included the restoration of hemostasis and safety measures. ResultsA total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted Thrombin Time or the ecarin clotting Time. In group A, 137 patients (45.5%) presented ...

  • Idarucizumab for Dabigatran Reversal
    The New England journal of medicine, 2015
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Peter Verhamme, Pieter W. Kamphuisen
    Abstract:

    BACKGROUND Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran. METHODS We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute Thrombin Time or ecarin clotting Time. A key secondary end point was the restoration of hemostasis. RESULTS This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute Thrombin Time and 81 with an elevated ecarin clotting Time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated. CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.)

Changsheng Zhao - One of the best experts on this subject based on the ideXlab platform.

  • zwitterionic glycosyl modified polyethersulfone membranes with enhanced anti fouling property and blood compatibility
    Journal of Colloid and Interface Science, 2015
    Co-Authors: Shuangsi Li, Tao Xiang, Xin Jiang, Rui Wang, Changsheng Zhao
    Abstract:

    Abstract In this study, novel zwitterionic glycosyl modified polyethersulfone (PES) ultrafiltration membranes were prepared via in-situ cross-linking polymerization coupled with phase inversion technique, and the following reactions. The membranes were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), 1HNMR spectrum, and static water contact angles (WCAs) measurements. The modified membranes showed excellent anti-fouling property, and the flux recovery ratio could reach almost 100%. Meanwhile, the blood compatibility of the membranes was measured by protein adsorption, platelet adhesion, activated partial thromboplastin Time (APTT), and Thrombin Time (TT). The results implied that the zwitterionic glycosyl modified PES membranes had good anti-fouling property and blood compatibility.

  • grafting of zwitterion from polysulfone membrane via surface initiated atrp with enhanced antifouling property and biocompatibility
    Journal of Membrane Science, 2013
    Co-Authors: Huijuan Li, Tao Xiang, Changsheng Zhao
    Abstract:

    Zwitterionic polymer of poly(sulfobetaine methacrylate) (PSBMA) was grafted from polysulfone (PSf) membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The polysulfone-graft-poly(sulfobetaine methacrylate) (PSf-g-PSBMA) membrane was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), attenuated total reflectance-Fourier transform infrared spectra (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and static water contact angle (WCA) measurement. The membrane showed excellent protein antifouling property though the water flux decreased to some content; nevertheless, the protein rejection ratio of the modified membrane was not change. The biocompatibility of the membrane was characterized by protein adsorption, hemolysis assay, platelet adhesion, plasma recalcification Time, activated partial thromboplastin Time (APTT), Thrombin Time (TT) and cytotoxicity experiments, and the results indicated that the modified PSf membrane had good blood compatibility and cytocompatibility.

  • grafting of zwitterion from polysulfone membrane via surface initiated atrp with enhanced antifouling property and biocompatibility
    Journal of Membrane Science, 2013
    Co-Authors: Huijuan Li, Tao Xiang, Changsheng Zhao
    Abstract:

    Zwitterionic polymer of poly(sulfobetaine methacrylate) (PSBMA) was grafted from polysulfone (PSf) membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The polysulfone-graft-poly(sulfobetaine methacrylate) (PSf-g-PSBMA) membrane was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), attenuated total reflectance-Fourier transform infrared spectra (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and static water contact angle (WCA) measurement. The membrane showed excellent protein antifouling property though the water flux decreased to some content; nevertheless, the protein rejection ratio of the modified membrane was not change. The biocompatibility of the membrane was characterized by protein adsorption, hemolysis assay, platelet adhesion, plasma recalcification Time, activated partial thromboplastin Time (APTT), Thrombin Time (TT) and cytotoxicity experiments, and the results indicated that the modified PSf membrane had good blood compatibility and cytocompatibility.

Charles V. Pollack - One of the best experts on this subject based on the ideXlab platform.

  • idarucizumab for dabigatran reversal full cohort analysis
    The New England Journal of Medicine, 2017
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Joanne Van Ryn
    Abstract:

    BackgroundIdarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. MethodsWe performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted Thrombin Time or ecarin clotting Time. Secondary end points included the restoration of hemostasis and safety measures. ResultsA total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted Thrombin Time or the ecarin clotting Time. In group A, 137 patients (45.5%) presented ...

  • Idarucizumab for Dabigatran Reversal
    The New England journal of medicine, 2015
    Co-Authors: Charles V. Pollack, Paul A. Reilly, Stephan Glund, Robert Dubiel, Richard A Bernstein, Menno V. Huisman, Elaine M Hylek, John W Eikelboom, Peter Verhamme, Pieter W. Kamphuisen
    Abstract:

    BACKGROUND Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran. METHODS We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding (group A) or required an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute Thrombin Time or ecarin clotting Time. A key secondary end point was the restoration of hemostasis. RESULTS This interim analysis included 90 patients who received idarucizumab (51 patients in group A and 39 in group B). Among 68 patients with an elevated dilute Thrombin Time and 81 with an elevated ecarin clotting Time at baseline, the median maximum percentage reversal was 100% (95% confidence interval, 100 to 100). Idarucizumab normalized the test results in 88 to 98% of the patients, an effect that was evident within minutes. Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79% of the patients. Among 35 patients in group A who could be assessed, hemostasis, as determined by local investigators, was restored at a median of 11.4 hours. Among 36 patients in group B who underwent a procedure, normal intraoperative hemostasis was reported in 33, and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient, respectively. One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated. CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.)