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Direct thrombin inhibitor

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https://www.readbyqxmd.com/read/29148253/quantification-of-vascular-damage-in-acute-kidney-injury-with-fluorine-magnetic-resonance-imaging-and-spectroscopy
#1
Jeremy K Moore, Junjie Chen, Hua Pan, Joseph P Gaut, Sanjay Jain, Samuel A Wickline
PURPOSE: To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. METHODS: A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone)...
November 16, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29135251/micellar-thrombin-binding-aptamers-reversible-nanoscale-anticoagulants
#2
Alexander Roloff, Andrea S Carlini, Cassandra E Callmann, Nathan C Gianneschi
Aptamers are nucleic acid-based ligands that exhibit promising features including specific and reversible target binding and inhibition. Aptamers can function as anticoagulants if they are directed against enzymes of the coagulation cascade. However, they typically suffer from nucleolytic digestion and fast clearance from the bloodstream. We present thrombin-binding aptamer amphiphiles that self-assemble into nanoscale polymeric micelles with a densely functionalized aptamer-displaying corona. We show that these micellar aptamers retain their native secondary structure in a crowded environment and are stabilized against degradation by nucleases in human serum...
November 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#3
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29117605/-new-oral-anticoagulants-noac-in-stroke-treatment
#4
Clemens Küpper, Lars Kellert, Steffen Tiedt, Frank Arne Wollenweber
Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only...
November 8, 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29105079/direct-oral-anticoagulants-versus-warfarin-for-preventing-stroke-and-systemic-embolic-events-among-atrial-fibrillation-patients-with-chronic-kidney-disease
#5
REVIEW
Miho Kimachi, Toshi A Furukawa, Kimihiko Kimachi, Yoshihito Goto, Shingo Fukuma, Shunichi Fukuhara
BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin...
November 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29100817/edoxaban-improves-acute-venous-thromboembolism-while-preserving-protein-c-and-protein-s-levels
#6
Hiromu Yamazaki, Shusuke Yagi, Yuta Torii, Rie Amano, Yasuyuki Oomichi, Teruaki Sangawa, Daiju Fukuda, Muneyuki Kadota, Takayuki Ise, Rie Ueno, Tomoya Hara, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata
BACKGROUND: It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. METHODS AND RESULTS: We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting...
October 31, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29093471/antithrombotic-properties-of-jj1-a-potent-and-novel-thrombin-inhibitor
#7
Wonhwa Lee, Suyeon Lee, Joonhyeok Choi, Jun-Hyeong Park, Kyung-Min Kim, Jun-Goo Jee, Jong-Sup Bae
The development of new anticoagulants is an important goal for the improvement of thrombosis treatment. Recent studies have suggested the importance of thrombin inhibitors in the modulation of thromboembolic disorders. The aim of this study was to discover a new small-molecule thrombin inhibitor. In this study, the compound JJ1, which has a novel scaffold, was selected by structure-based docking simulation to determine its potential inhibitory activity against thrombin. JJ1 was shown to inhibit the catalytic activity of human α-thrombin with a K i of 0...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089725/evidence-for-idarucizumab-praxbind-in-the-reversal-of-the-direct-thrombin-inhibitor-dabigatran-review-following-the-re-verse-ad-full-cohort-analysis
#8
Timothy C Hutcherson, Nicole E Cieri-Hutcherson, Rajvi Bhatt
Idarucizumab is the first reversal agent approved for the direct thrombin inhibitor dabigatran. The authors summarize the findings from the clinical trial series and describe case reports, post-marketing data, and ongoing studies.
November 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/29077405/discovery-of-a-parenteral-small-molecule-coagulation-factor-xia-inhibitor-clinical-candidate-bms-962212
#9
Donald J P Pinto, Michael J Orwat, Leon M Smith, Mimi L Quan, Patrick Y S Lam, Karen A Rossi, Atsu Apedo, Jeffrey M Bozarth, Yiming Wu, Joanna J Zheng, Baomin Xin, Nathalie Toussaint, Paul Stetsko, Olafur Gudmundsson, Brad Maxwell, Earl J Crain, Pancras C Wong, Zhen Lou, Timothy W Harper, Silvi A Chacko, Joseph E Myers, Steven Sheriff, Huiping Zhang, Xiaoping Hou, Arvind Mathur, Dietmar A Seiffert, Ruth R Wexler, Joseph M Luettgen, William R Ewing
Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding. On the basis of this potential, we targeted our efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic agent for use in a hospital setting...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29076942/evaluation-of-systemic-heparin-versus-bivalirudin-in-adult-patients-supported-by-extracorporeal-membrane-oxygenation
#10
Theodore J Berei, Matthew P Lillyblad, Kelly J Wilson, Ross F Garberich, Katarzyna M Hryniewicz
Systemic anticoagulation is a standard of care in adult patients supported by extracorporeal membrane oxygenation (ECMO) to prevent circuit thrombosis and subsequent thromboembolic events. Unfractionated heparin has long been considered the anticoagulant of choice, but emerging evidence reports successful ECMO runs with direct thrombin inhibitors. This retrospective study sought to determine whether bivalirudin offers distinct clinical benefits as the anticoagulant of choice in ECMO. Primary end points included thrombotic events during the initial 96 hours of anticoagulation, over the course of their entire ECMO run, and at any time during the admission, as well as in-hospital and 30-day mortality...
October 23, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/29072911/the-design-of-small-molecule-active-site-inhibitors-of-the-s1a-family-proteases-as-procoagulant-and-anticoagulant-drugs
#11
Peter M Fischer
Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose-response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains...
October 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29066639/idiopathic-catastrophic-thrombosis-with-happy-ending
#12
Julia Heid, Andreas Greinacher, Hugo A Katus, Oliver J Müller
A 59-year-old male patient suffered three life-threatening instent thromboses after an initial resuscitation due to an ST-segment elevation myocardial infarction of the anterior cardiac wall. With a high-risk profile for heparin-induced thrombocytopenia (HIT), he was placed on argatroban after the second reinfarction. Under this apparently appropriate treatment, a third reinfarction occurred, and the patient had to undergo high-risk cardiac bypass surgery. Later on, a deep vein thrombosis and an intracardiac thrombus formed...
October 23, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29059268/evaluation-of-a-reflex-testing-algorithm-for-suspected-heparin-induced-thrombocytopenia
#13
Chad M Vanderbilt, Craig McFarland, Stuart E Lind
Objectives: We implemented a policy of reflex serotonin-release assay (SRA) testing for all patients with a positive heparin-induced thrombocytopenia (HIT) immunoassay. Methods: We identified all patients who had SRA testing sent as a consequence of a positive HIT immunoassay test. We reviewed charts of patients to calculate the 4Ts clinical score, determined the effect of testing on clinical management, and documented the change in utilization of direct thrombin inhibitors (DTIs)...
November 2, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29053656/is-it-necessary-to-alter-anticoagulation-therapy-for-tooth-extraction-in-patients-taking-direct-oral-anticoagulants
#14
M Caliskan, H-C Tükel, M-E Benlidayi, A Deniz
BACKGROUND: The number of patients using direct oral anticoagulants (DOACs) instead of vitamin K antagonists (VKA) is increasing and there is limited data on the safety of tooth extractions in patients taking DOACs. The aim of this study was to compare the amount of bleeding (AOB) and postoperative complications after tooth extractions between patients taking VKAs and patients taking DOACs without altering the anticoaguation therapy. MATERIAL AND METHODS: The study consisted of four groups: Direct thrombin inhibitor group, factor Xa inhibitor group, warfarin group and a control group...
November 1, 2017: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/29050502/first-evidence-trap-induced-platelet-aggregation-is-reduced-in-patients-receiving-xabans
#15
Frantisek Nehaj, Juraj Sokol, Jela Ivankova, Michal Mokan, Frantisek Kovar, Jan Stasko, Marian Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29040496/changes-in-platelet-bax-levels-contribute-to-impaired-platelet-response-to-thrombin-after-cardiopulmonary-bypass-prospective-observational-clinical-and-laboratory-investigations
#16
M Murase, Y Nakayama, D I Sessler, N Mukai, S Ogawa, Y Nakajima, Hugh C Hemmings
Background: Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery ( n =20 each)...
December 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29032872/assessing-bleeding-risk-in-patients-with-intentional-overdoses-of-novel-antiplatelet-and-anticoagulant-medications
#17
Michael Levine, Michael C Beuhler, Anthony Pizon, F Lee Cantrel, Meghan B Spyres, Frank LoVecchio, Aaron B Skolnik, Daniel E Brooks
STUDY OBJECTIVE: In recent years, the use of novel anticoagulants and antiplatelet agents has become widespread. Little is known about the toxicity and bleeding risk of these agents after acute overdose. The primary objective of this study is to evaluate the relative risk of all bleeding and major bleeding in patients with acute overdose of novel antiplatelet and anticoagulant medications. METHODS: This study is a retrospective study of acute ingestion of apixaban, clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and ticagrelor reported to 7 poison control centers in 4 states during a 10-year span...
October 9, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28993777/the-procoagulant-activity-of-apoptotic-cells-is-mediated-by-interaction-with-factor-xii
#18
Aizhen Yang, Fengwu Chen, Chao He, Junsong Zhou, Yi Lu, Jihong Dai, Raymond B Birge, Yi Wu
Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system. The purpose of this study was to determine whether FXII is involved in procoagulant activity of apoptotic cells. Using western blotting and chromogenic substrate assay, we found that incubation with apoptotic cells, but not with viable cells, resulted in rapid cleavage and activation of FXII in the presence of prekallikrein and high molecular weight kininogen (HK), other two components of contact activation system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28993605/a-case-of-diffuse-alveolar-hemorrhage-as-a-possible-complication-of-bivalirudin-therapy
#19
Htun Latt, Sammy Aung, Kyaw Kyaw, Thein Tun Aung, Chanwit Roongsritong
BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal complication of anticoagulant or antiplatelet therapy. Bivalirudin is a specific and reversible direct thrombin inhibitor (DTI). CASE REPORT We report a case of severe DAH, possibly related to bivalirudin use, in a 61-year-old patient undergoing coronary intervention. The patient had presented with an out-of-hospital cardiac arrest due to acute ST elevation myocardial infarction (STEMI). During the coronary intervention, shortly after receiving bivalirudin, the patient started having frank bleeding from the endotracheal tube and developed hemodynamic compromise...
October 10, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28979172/reversing-factor-xa-inhibitors-clinical-utility-of-andexanet-alfa
#20
REVIEW
Scott Kaatz, Hardik Bhansali, Joseph Gibbs, Robert Lavender, Charles E Mahan, David G Paje
Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications...
2017: Journal of Blood Medicine
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