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Direct thrombin inhibitor

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https://www.readbyqxmd.com/read/29338293/betrixaban-a-new-oral-factor-xa-inhibitor-for-extended-venous-thromboembolism-prophylaxis-in-high-risk-hospitalized-patients
#1
Scott G Garland, Christina E DeRemer, Steven M Smith, John G Gums
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of acute medically ill patients with venous thromboembolism (VTE) risk factors. DATA SOURCES: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral anticoagulant, TSOAC...
January 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29335786/anti-inflammatory-and-antiplatelet-effects-of-non-vitamin-k-antagonist-oral-anticoagulants-in-acute-phase-of-ischemic-stroke-patients
#2
Taizen Nakase, Junta Moroi, Tatsuya Ishikawa
BACKGROUND: Recently, non-vitamin K antagonist oral anticoagulants such as direct thrombin and direct factor Xa inhibitors have been prescribed for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients. This study aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in the clinical setting of acute ischemic stroke...
January 12, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29325495/management-of-cancer-associated-venous-thromboembolism-a-case-based-practical-approach
#3
Minna Voigtlaender, Florian Langer
In patients with solid tumours or haematological malignancies, venous thromboembolism (VTE) is a leading cause of death and significantly contributes to morbidity and healthcare resource utilization. Current practice guidelines recommend long-term anticoagulation with low-molecular-weight heparin (LMWH) as the treatment of choice for cancer-associated VTE, based on clinical trial data showing an overall improved safety and efficacy profile of LMWH compared to vitamin K antagonists. However, several open questions remain, e...
January 12, 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29319249/stroke-prevention-in-atrial-fibrillation-which-is-the-best-balanced-in-efficacy-and-safety-as-a-thromboprophylactic
#4
Viraj Suvarna
Stroke prevention in atrial fibrillation (AF) has reached an exciting phase with a plethora of newer, potentially more efficacious and safer agents being introduced for physicians to select from. Dabigatran belongs to a class of anticoagulants called direct thrombin inhibitors, while rivaroxaban, apixaban, and edoxaban are direct Factor Xa inhibitors. Purely from a therapeutic endpoint perspective-based on the action of anticoagulants in reducing cardioembolic stroke-in clinical trials, one should look at whether a new anticoagulant in patients with AF prevents ischemic stroke...
October 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29318007/severe-haematuria-of-lower-urinary-tract-origin-with-low-dose-dabigatran-use-in-three-indian-elderly-patients-unresolved-issues-in-the-safety-of-novel-oral-anticoagulants
#5
Upinder Kaur, Sankha Shubhra Chakrabarti, Sukdev Manna, Indrajeet Singh Gambhir
Dabigatran is a newer oral direct thrombin inhibitor approved by the United States Food and Drug Administration and the European Medicines Agency (EMA). The proper dosage of the drug, the potential for adverse drug reactions and the nature of bleeds with use of this drug as with other novel oral anticoagulants (NOACs), in the elderly population are still areas of uncertainty. Despite the existence of a specific antibody, idarucizumab which is an antidote to dabigatran toxicity, management of dabigatran-induced bleeds is an undefined area especially in resource constrained settings...
January 2018: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/29314632/comparison-of-five-specific-assays-for-determination-of-dabigatran-plasma-concentrations-in-patients-enrolled-in-the-start-laboratory-register
#6
M Cini, C Legnani, B Cosmi, S Testa, C Dellanoce, O Paoletti, R Marcucci, D Poli, R Paniccia, V Pengo, A Tripodi, G Palareti
INTRODUCTION: Several specific assays are commercially available to determine dabigatran anticoagulant activity. Aims of this multicenter and multiplatform study were to compare five methods for dabigatran measurement and investigate their performances in the low concentration range. METHODS: Dabigatran levels were analyzed in 295 plasma samples from patients enrolled in the START-Laboratory Register by the following methods using dedicated calibrators and controls: STA-ECA II (Diagnostica Stago), standard and low range Hemoclot Thrombin Inhibitors (Hyphen BioMed), Direct Thrombin Inhibitor Assay (Instrumentation Laboratory), Direct Thrombin Inhibitor Assay (Siemens), Technoclot DTI (Technoclone)...
January 3, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29296829/safety-pharmacokinetics-and-reversal-of-apixaban-anticoagulation-with-andexanet-alfa
#7
Deborah Siegal, Genmin Lu, Janet M Leeds, Mark Karbarz, Janice Castillo, Vandana Mathur, Athiwat Hutchaleelaha, Uma Sinha, Michael Kitt, Matt McClure, Stanley J Hollenbach, John T Curnutte, Pamela B Conley, Mark Crowther
Direct factor Xa (FXa) inhibitors lack a specific reversal agent for emergencies such as major bleeding or urgent surgery. Andexanet alfa, a modified, catalytically inactive, recombinant human FXa derivative, reverses anticoagulant effect by binding and sequestering FXa inhibitors. This original report of safety and dose-finding, phase 1 and 2 randomized, double-blind, placebo-controlled studies, investigated various doses of andexanet in healthy volunteers. Phase 1 evaluated the safety and pharmacokinetics of andexanet (n = 24) or placebo (n = 8)...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295790/direct-oral-anticoagulants-an-update
#8
REVIEW
Ana Isabel Franco Moreno, Rosa María Martín Díaz, María José García Navarro
Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome...
December 30, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/29277148/prostacyclins-in-cardiac-surgery-coming-of-age
#9
Seema P Deshpande, Michael A Mazzeffi, Erik Strauss, Allison Hollis, Kenichi A Tanaka
Prostacyclin (prostaglandin I2 [PGI2]) is an eicosanoid lipid mediator produced by the endothelial cells. It plays pivotal roles in vascular homeostasis by virtue of its potent vasodilatory and antithrombotic effects. Stable pharmacological analogues of PGI2 are used for treatment of pulmonary hypertension and right ventricular failure. PGI2 dose dependently inhibits platelet activation induced by adenosine-5'-diphosphate, arachidonic acid, collagen, and low-dose thrombin. This property has led to its use as an alternative to direct thrombin inhibitors in patients with type II heparin-induced thrombocytopenia (HIT) undergoing cardiac surgery...
December 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29242919/association-of-novel-oral-antithrombotics-with-the-risk-of-intraocular-bleeding
#10
Katherine E Uyhazi, Todd Miano, Wei Pan, Brian L VanderBeek
Importance: Novel oral anticoagulation and antiplatelet therapies have become a mainstay of treatment for thromboembolic disease. However, the safety profile of these medications has not been completely characterized. Objective: To determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents. Design, Setting, and Participants: In this retrospective cohort study, a large national insurance claims database was used to generate 2 parallel analyses...
December 14, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29239808/drug-class-renal-elimination-and-outcomes-of-direct-oral-anticoagulants-in-asian-patients-a-meta-analysis
#11
Kang-Ling Wang, Chun-Chih Chiu, Robert P Giugliano, Doreen Su-Yin Tan, Chun-Yi Lin, En-Yu Lai, Shinya Goto, Chern-En Chiang
BACKGROUND: Direct oral anticoagulants (DOACs) have a better risk benefit profile in Asian patients with atrial fibrillation (AF). Whether treatment effects could be modified by drug class and dependency on renal elimination of studied agents has not yet been explored. METHODS: We searched PubMed, CENTRAL, and CINAHL databases through November 2016 for phase III randomized controlled trials comparing DOACs with warfarin in patients with AF. Efficacy and safety outcomes were pooled according to drug class and dependency on renal elimination of DOACs and were compared with the Mantel-Haenszel fixed-effects model...
November 24, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29213245/implication-of-free-fatty-acids-in-thrombin-generation-and-fibrinolysis-in-vascular-inflammation-in-zucker-rats-and-evolution-with-aging
#12
Jérémy Lagrange, Mélusine Didelot, Amel Mohamadi, Lucy A Walton, Saartje Bloemen, Bas de Laat, Huguette Louis, Simon N Thornton, Brian Derby, Michael J Sherratt, Bruno Fève, Pascal Challande, Riaz Akhtar, J Kennedy Cruickshank, Patrick Lacolley, Véronique Regnault
Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis. Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29212124/diagnostic-accuracy-of-a-novel-chromogenic-direct-thrombin-inhibitor-assay-clinical-experiences-for-dabigatran-monitoring
#13
Sven Poli, Florian Härtig, Charlotte Spencer, Matthias Ebner, Ingvild Birschmann, Joachim Kuhn, Susanne Faix, Ulf Ziemann, Hans-Ulrich Häring, Rainer Lehmann, Andreas Peter, Sebastian Hörber
No abstract text is available yet for this article.
December 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29199435/-laboratory-aspects-of-novel-oral-anticoagulant-treatment
#14
Zsuzsanna Bereczky, Zsolt Oláh, Éva Ajzner, János Kappelmayer
The introduction of novel oral anticoagulants (NOAC) have long been expected drugs and they quickly became used widespread as their clinical effectiveness was as good as, or even better than the previously used only oral anticoagulant drug, the coumarins. Thus, the direct thrombin inhibitor dabigatran and the activated factor X inhibitors (rivaroxaban, apixaban, edoxaban) have become the part of daily therapeutic practice. Their permeation was facilitated by the guideline which suggested that no laboratory monitoring was required during NOAC treatment and this was very convenient for both patients and doctors...
December 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29193875/dabigatran-inhibits-intravitreal-thrombin-activity
#15
Jeroen Bastiaans, Verena C Mulder, Jan C van Meurs, Marja Smits-Te Nijenhuis, Conny van Holten-Neelen, P Martin van Hagen, Willem A Dik
PURPOSE: Proliferative vitreoretinopathy (PVR) is a vitreoretinal disorder in which retinal pigment epithelial (RPE) cell activation contributes to both formation of fibrotic retinal membranes and inflammation. Vitreous of patients with PVR contains increased thrombin activity which induces profibrotic and proinflammatory programs in RPE cells. Inhibition of intravitreal thrombin activity may thus represent a therapeutic option for PVR. In this study, we examined the capacity of the clinically available direct thrombin inhibitor dabigatran to inhibit thrombin activity in vitreous fluids...
November 30, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29185142/initial-and-long-term-impact-of-a-multi-disciplinary-task-force-in-the-diagnosis-and-management-of-heparin-induced-thrombocytopenia
#16
Ming Y Lim, Joyce Foster, Angela Rourk, Charles S Greenberg
Many medical centers are faced with a major challenge in making an accurate diagnosis of heparin-induced thrombocytopenia (HIT) and ensuring appropriate changes in management strategy in line with guideline recommendations. We report the initial and long-term impact and challenges of institution-wide changes in the diagnosis and management of HIT in the inpatient setting at an academic medical center. We established a HIT Task Force, consisting of a multidisciplinary team of non-malignant hematologists, nursing, pharmacist, pathology, blood bank and clinical lab informatics...
November 28, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29176379/thrombin-generation-estimates-the-anticoagulation-effect-of-direct-oral-anticoagulants-with-significant-interindividual-variability-observed
#17
Joseph Rigano, Cheryl Ng, Harshal Nandurkar, Prahlad Ho
: Direct oral anticoagulants (DOACs) are increasingly being used, primarily due to their drug stability and patient convenience. Although these drugs have been evaluated to be well tolerated in numerous clinical trials, their impact on in-vivo anticoagulation effect, variability and therapeutic drug level remains unknown. Hence, we aim to study the effect and variability of DOACs on thrombin generation via the calibrated automated thrombogram. Anonymized coagulation specimens from outpatients on warfarin were collected...
November 25, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29175298/does-type-2-diabetes-affect-the-on-treatment-levels-of-direct-oral-anticoagulants-in-patients-with-atrial-fibrillation
#18
Matej Samoš, Tomáš Bolek, Lucia Stančiaková, Ingrid Škorňová, Jela Ivanková, František Kovář, Peter Galajda, Peter Kubisz, Ján Staško, Marián Mokáň
AIMS: Type 2 diabetes (T2D) is connected with several abnormalities in haemostasis; and with higher risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NV-AF). However, it is recently unknown whether T2D affects the activity of direct oral anticoagulants (DOACs). The aim of this study was to determine the impact of T2D on DOACs activity in patients with NV-AF. METHODS: This pilot prospective study enrolled totally 65 patients with NV-AF (20 dabigatran-treated, 110 mg/twice daily; 28 rivaroxaban-treated, 15 mg/daily; 17 apixaban-treated, 5 mg/twice daily)...
November 23, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29148253/quantification-of-vascular-damage-in-acute-kidney-injury-with-fluorine-magnetic-resonance-imaging-and-spectroscopy
#19
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
#20
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
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