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  1. Article ; Online: Out of Control: Why Randomized Trials of Factor Concentrates Are So Elusive.

    Thalji, Nabil K / Patel, Prakash A

    Journal of cardiothoracic and vascular anesthesia

    2021  Volume 35, Issue 9, Page(s) 2659–2661

    MeSH term(s) Factor VIII ; Hemophilia A ; Humans ; Randomized Controlled Trials as Topic
    Chemical Substances Factor VIII (9001-27-8)
    Language English
    Publishing date 2021-06-12
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1067317-9
    ISSN 1532-8422 ; 1053-0770
    ISSN (online) 1532-8422
    ISSN 1053-0770
    DOI 10.1053/j.jvca.2021.06.011
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  2. Article ; Online: Hematologic Consequences of the Coronavirus Crisis-Focus on Relevant Clues and Complications for the Perioperative Cardiothoracic and Vascular Community.

    Thalji, Nabil K / Patel, Prakash A / Elliott, Matthew / Augoustides, John G

    Journal of cardiothoracic and vascular anesthesia

    2020  Volume 34, Issue 12, Page(s) 3189–3192

    MeSH term(s) Anesthesia, Cardiac Procedures/standards ; Blood Cell Count/standards ; Blood Coagulation/physiology ; COVID-19/epidemiology ; COVID-19/therapy ; Cardiac Surgical Procedures/standards ; Hematologic Diseases/blood ; Hematologic Diseases/epidemiology ; Hematologic Diseases/therapy ; Humans ; Perioperative Care/standards
    Keywords covid19
    Language English
    Publishing date 2020-05-27
    Publishing country United States
    Document type Editorial
    ZDB-ID 1067317-9
    ISSN 1532-8422 ; 1053-0770
    ISSN (online) 1532-8422
    ISSN 1053-0770
    DOI 10.1053/j.jvca.2020.05.032
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  3. Article ; Online: Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.

    Thalji, Nabil K / Camire, Rodney M

    Current opinion in hematology

    2017  Volume 24, Issue 5, Page(s) 453–459

    Abstract: Purpose of review: New therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future ... ...

    Abstract Purpose of review: New therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future development prospects.
    Recent findings: Underlying many procoagulant therapeutic approaches is the rapid generation of thrombin to promote robust clot formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide effective hemostasis to mitigate bleeding in hemophilia and other clinical situations. Over the past decade, we explored the possibility of using zymogen-like factor Xa variants to rapidly improve clot formation for the treatment of bleeding conditions. Compared to the wild-type enzyme, these variants adopt an altered, low activity, conformation which enables them to resist plasma protease inhibitors. However, zymogen-like factor Xa variants are conformationally dynamic and ligands such as its cofactor, factor Va, stabilize the molecule rescuing procoagulant activity. At the site of vascular injury, the variants in the presence of factor Va serve as effective prohemostatic agents. Preclinical data support their use to stop bleeding in a variety of clinical settings. Phase 1 studies suggest that zymogen-like factor Xa is safe and well tolerated, and a phase 1b is ongoing to assess safety in patients with intracerebral hemorrhage.
    Summary: Zymogen-like factor Xa is a unique prohemostatic agent for the treatment of a range of bleeding conditions.
    MeSH term(s) Blood Coagulation/drug effects ; Clinical Trials, Phase I as Topic ; Enzyme Precursors/therapeutic use ; Factor Va/metabolism ; Factor Xa/therapeutic use ; Hemorrhage/blood ; Hemorrhage/drug therapy ; Hemostatic Techniques ; Humans
    Chemical Substances Enzyme Precursors ; Factor Va (65522-14-7) ; Factor Xa (EC 3.4.21.6)
    Language English
    Publishing date 2017-06-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1153887-9
    ISSN 1531-7048 ; 1065-6251
    ISSN (online) 1531-7048
    ISSN 1065-6251
    DOI 10.1097/MOH.0000000000000369
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  4. Article ; Online: Opioid-Free Cardiac Surgery: A Multimodal Pain Management Strategy With a Focus on Bilateral Erector Spinae Plane Block Catheters.

    Thalji, Nabil K / Patel, Saumil Jayant / Augoustides, John G / Schiller, Robin J / Dalia, Adam A / Low, Yinghui / Hamzi, Rawad I / Fernando, Rohesh J

    Journal of cardiothoracic and vascular anesthesia

    2022  Volume 36, Issue 12, Page(s) 4523–4533

    MeSH term(s) Humans ; Pain Management ; Analgesics, Opioid ; Nerve Block ; Cardiac Surgical Procedures/adverse effects ; Catheters ; Pain, Postoperative/etiology ; Pain, Postoperative/prevention & control
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2022-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1067317-9
    ISSN 1532-8422 ; 1053-0770
    ISSN (online) 1532-8422
    ISSN 1053-0770
    DOI 10.1053/j.jvca.2022.09.002
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  5. Article ; Online: Left Coronary Artery Reimplantation for Repair of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery in an Adult.

    Chahal, Navdeep K / Horak, Jiri G / Thalji, Nabil K / Augoustides, John G / Garner, Chandrika R / Bradshaw, John D / Fernando, Rohesh J / Krishnan, Sandeep / Desai, Ronak G / Patel, Kinjal M

    Journal of cardiothoracic and vascular anesthesia

    2023  Volume 37, Issue 10, Page(s) 2098–2108

    MeSH term(s) Humans ; Adult ; Infant ; Coronary Vessels/diagnostic imaging ; Coronary Vessels/surgery ; Pulmonary Artery/diagnostic imaging ; Pulmonary Artery/surgery ; Pulmonary Artery/abnormalities ; Coronary Vessel Anomalies/diagnostic imaging ; Coronary Vessel Anomalies/surgery ; Treatment Outcome ; Replantation
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1067317-9
    ISSN 1532-8422 ; 1053-0770
    ISSN (online) 1532-8422
    ISSN 1053-0770
    DOI 10.1053/j.jvca.2023.06.036
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  6. Article ; Online: Hematological Consequences of the Coronavirus Crisis – focus on relevant clues and complications for the perioperative cardiothoracic and vascular community

    Thalji, Nabil K. / Patel, Prakash A. / Elliott, Matthew / Augoustides, John G.

    J Cardiothorac Vasc Anesth

    Keywords covid19
    Publisher Elsevier; PMC; WHO
    Document type Article ; Online
    Note WHO #Covidence: #381761
    DOI 10.1053/j.jvca.2020.05.032
    Database COVID19

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  7. Article: Hematologic Consequences of the Coronavirus Crisis-Focus on Relevant Clues and Complications for the Perioperative Cardiothoracic and Vascular Community

    Thalji, Nabil K / Patel, Prakash A / Elliott, Matthew / Augoustides, John G

    J. cardiothoracic vasc. anest

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #611535
    Database COVID19

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  8. Article ; Online: A rapid pro-hemostatic approach to overcome direct oral anticoagulants.

    Thalji, Nabil K / Ivanciu, Lacramioara / Davidson, Robert / Gimotty, Phyllis A / Krishnaswamy, Sriram / Camire, Rodney M

    Nature medicine

    2016  Volume 22, Issue 8, Page(s) 924–932

    Abstract: Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that are becoming widely adopted. The ability to reverse their anticoagulant effects is important when serious bleeding occurs or urgent medical procedures are ...

    Abstract Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that are becoming widely adopted. The ability to reverse their anticoagulant effects is important when serious bleeding occurs or urgent medical procedures are needed. Here, using experimental mouse models of hemostasis, we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence of the anticoagulant effects of these inhibitors. The ability of FXa(I16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability of the active site inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa to persist in plasma. Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis models tested than a noncatalytic antidote that is currently in clinical development. FXa(I16L) also reduces the anticoagulant-associated bleeding in vivo that is induced by the thrombin inhibitor dabigatran. FXa(I16L) may be able to fill an important unmet clinical need for a rapid, pro-hemostatic agent to reverse the effects of several new anticoagulants.
    MeSH term(s) Animals ; Antidotes/pharmacology ; Blood Coagulation/drug effects ; Factor Xa/chemistry ; Factor Xa/pharmacology ; Factor Xa Inhibitors/pharmacology ; Hemostasis/drug effects ; Humans ; In Vitro Techniques ; Mice ; Rivaroxaban/pharmacology ; Thrombelastography
    Chemical Substances Antidotes ; Factor Xa Inhibitors ; Rivaroxaban (9NDF7JZ4M3) ; Factor Xa (EC 3.4.21.6)
    Language English
    Publishing date 2016-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm.4149
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  9. Article ; Online: Kinetic mechanism and structural requirements of the amine-catalyzed decarboxylation of oxaloacetic acid.

    Thalji, Nabil K / Crowe, William E / Waldrop, Grover L

    The Journal of organic chemistry

    2009  Volume 74, Issue 1, Page(s) 144–152

    Abstract: The kinetic and chemical mechanism of amine-catalyzed decarboxylation of oxaloacetic acid at pH 8.0 has been reevaluated using a new and versatile assay. Amine-catalyzed decarboxylation of oxaloacetic acid proceeds via the formation of an imine ... ...

    Abstract The kinetic and chemical mechanism of amine-catalyzed decarboxylation of oxaloacetic acid at pH 8.0 has been reevaluated using a new and versatile assay. Amine-catalyzed decarboxylation of oxaloacetic acid proceeds via the formation of an imine intermediate, followed by decarboxylation of the intermediate and hydrolysis to yield pyruvate. The decrease in oxaloacetic acid was coupled to NADH formation by malate dehydrogenase, which allowed the rates of both initial carbinolamine formation (as part of the imination step) and decarboxylation to be determined. By comparing the rates observed for a variety of amines and, in particular, diamines, the structural and electronic requirements for diamine-catalyzed decarboxylation at pH 8.0 were identified. At pH 8.0, monoamines were found to be very poor catalysts, whereas some diamines, most notably ethylenediamine, were excellent catalysts. The results indicate that the second amino group of diamines enhances the rate of imine formation by acting as a proton shuttle during the carbinolamine formation step, which enables diamines to overcome high levels of solvation that would otherwise inhibit carbinolamine, and thus imine, formation. The presence of the second amino group may also enhance the rate of the carbinolamine dehydration step. In contrast to the findings of previous reports, the second amino group participates in the reaction by enhancing the rate of decarboxylation via hydrogen-bonding to the imine nitrogen to either stabilize the negative charge that develops on the imine during decarboxylation or preferentially stabilize the reactive imine over the unreactive enamine tautomer. These results provide insight into the precise catalytic mechanism of several enzymes whose reactions are known to proceed via an imine intermediate.
    MeSH term(s) Amines/chemistry ; Catalysis ; Decarboxylation ; Hydrolysis ; Kinetics ; Molecular Conformation ; Oxaloacetates/chemistry ; Pyruvic Acid/chemical synthesis ; Pyruvic Acid/chemistry ; Stereoisomerism
    Chemical Substances Amines ; Oxaloacetates ; Pyruvic Acid (8558G7RUTR)
    Language English
    Publishing date 2009-01-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123490-0
    ISSN 1520-6904 ; 0022-3263
    ISSN (online) 1520-6904
    ISSN 0022-3263
    DOI 10.1021/jo8014648
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    Zs.A 4473: Show issues Location:
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  10. Article ; Online: Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

    Gunaratne, Ruwan / Kumar, Shekhar / Frederiksen, James W / Stayrook, Steven / Lohrmann, Jens L / Perry, Kay / Bompiani, Kristin M / Chabata, Charlene V / Thalji, Nabil K / Ho, Michelle D / Arepally, Gowthami / Camire, Rodney M / Krishnaswamy, Sriram / Sullenger, Bruce A

    Nature biotechnology

    2018  Volume 36, Issue 7, Page(s) 606–613

    Abstract: Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve ... ...

    Abstract Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.
    MeSH term(s) Anticoagulants/administration & dosage ; Anticoagulants/chemistry ; Aptamers, Nucleotide/administration & dosage ; Aptamers, Nucleotide/chemistry ; Aptamers, Nucleotide/genetics ; Cardiopulmonary Bypass/adverse effects ; Crystallography, X-Ray ; Drug Combinations ; Factor Xa/chemistry ; Factor Xa/genetics ; Factor Xa Inhibitors/administration & dosage ; Factor Xa Inhibitors/chemistry ; Heparin/adverse effects ; Humans ; Postoperative Hemorrhage/drug therapy ; Postoperative Hemorrhage/genetics ; Postoperative Hemorrhage/pathology ; Protein Conformation/drug effects
    Chemical Substances Anticoagulants ; Aptamers, Nucleotide ; Drug Combinations ; Factor Xa Inhibitors ; Heparin (9005-49-6) ; Factor Xa (EC 3.4.21.6)
    Language English
    Publishing date 2018-06-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/nbt.4153
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