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https://www.readbyqxmd.com/read/28682477/preclinical-safety-and-efficacy-of-andexanet-alfa-in-animal-models
#1
G Lu, S J Hollenbach, D C Baker, S Tan, A Hutchaleelaha, J T Curnutte, P B Conley
BACKGROUND: Andexanet is a recombinant modified form of factor Xa (FXa), designed to bind to and reverse the anticoagulant activity of FXa inhibitors. OBJECTIVES: To evaluate the ability of andexanet to reverse the anticoagulant activity of rivaroxaban, and assess its pharmacokinetics (PK) and toxicity in animal models. METHODS: The effects of andexanet on blood loss, anti-FXa activity, rivaroxaban unbound plasma concentrations, and other coagulation parameters were assessed in a rabbit liver laceration 'treatment' model...
July 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28650000/andexanet-alfa-a-recombinant-mimetic-of-human-factor-xa-for-the-reversal-of-anticoagulant-therapies
#2
G Escolar, M Diaz-Ricart, E Arellano-Rodrigo
Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28639882/management-of-oral-anticoagulation-therapy-after-gastrointestinal-bleeding-whether-to-when-to-and-how-to-restart-an-anticoagulation-therapy
#3
Kazuhiko Kido, Michael J Scalese
OBJECTIVE: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. DATA SOURCES: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28625215/assessing-coagulation-by-rotational-thromboelastometry-rotem-in-rivaroxaban-anticoagulated-blood-using-hemostatic-agents
#4
Jonathan Bar, Alexa David, Tarek Khader, Mary Mulcare, Christopher Tedeschi
Introduction The use of direct oral anticoagulants (DOACs) such as rivaroxaban (Xarelto) is increasingly common. However, therapies for reversing anticoagulation in the event of hemorrhage are limited. This study investigates the ability of hemostatic agents to improve the coagulation of rivaroxaban-anticoagulated blood, as measured by rotational thromboelastometry (ROTEM). Hypothesis/Problem If a chitosan-based hemostatic agent (Celox), which works independently of the clotting cascade, is applied to rivaroxaban-anticoagulated blood, it should improve coagulation by decreasing clotting time (CT), decreasing clot formation time (CFT), and increasing maximum clot firmness (MCF)...
June 19, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28594426/new-developments-in-anticoagulants-past-present-and-future
#5
Jeffrey I Weitz, Job Harenberg
Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients...
June 28, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28536415/late-obstructive-transcatheter-heart-valve-thrombosis-resolved-by-rivaroxaban
#6
Ole Norling Mathiassen, Erik Lerkevang Grove, Nicolaj Christoffer Hansson, Bjarne Linde Norgaard
BACKGROUND Although transcatheter aortic valve replacement (TAVR) has become a worldwide and generally accepted treatment of patients with aortic stenosis at high surgical risk, there is a rising concern and debate about the occurrence of transcatheter heart valve (THV) thrombosis and its impact on TAVR outcome. It seems that the incidence of THV thrombosis is higher than first anticipated, but uncertainty remains regarding how to prevent and how to treat it. Hence, there is an urgent need for understanding THV thrombosis and to communicate experiences within the field...
May 24, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28498476/effects-of-unfractionated-heparin-and-rivaroxaban-on-the-expression-of-heparanase-and-fibroblast-growth-factor-2-in-human-osteoblasts
#7
Jingjun Xia, Wei Sheng, Liubao Pei, Ning Li, Zhipeng Zhang, Jialiang Wang, Jianing Zu, Nanxiang Wang, Duanyang Wang
Long-term treatment with anticoagulants may contribute to osteoporosis. Although unfractionated heparin and rivaroxaban have adverse effects on bone microstructure and function in adult rats, the underlying mechanism remains to be elucidated. Heparanase (HPSE) and fibroblast growth factor (FGF)2 are important signals in bone formation and fracture healing. Therefore, the present study was designed to investigate the effects of unfractionated heparin and rivaroxaban on the expression of HPSE and FGF2 in human osteoblasts...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28429198/managing-the-perioperative-patient-on-direct-oral-anticoagulants
#8
Jordan Leitch, Janet van Vlymen
PURPOSE: Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery...
June 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28412907/review-of-the-pharmacology-of-the-emerging-possibilities-of-the-direct-oral-anticoagulants-reversal
#9
Matej Samos, Lucia Stanciakova, Ingrid Skornova, Tomas Bolek, Frantisek Kovar, Jan Stasko, Peter Galajda, Marian Mokan, Peter Kubisz
BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with non-valvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients...
April 13, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28373761/gastrointestinal-bleeding-in-patients-on-novel-oral-anticoagulants-risk-prevention-and-management
#10
REVIEW
Ka-Shing Cheung, Wai K Leung
Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b...
March 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28366075/importance-of-balancing-follow-up-time-and-impact-of-oral-anticoagulant-users-selection-when-evaluating-medication-adherence-in-atrial-fibrillation-patients-treated-with-rivaroxaban-and-apixaban
#11
Craig Coleman, Zhong Yuan, Jeff Schein, Concetta Crivera, Veronica Ashton, François Laliberté, Patrick Lefebvre, Eric D Peterson
OBJECTIVE: Studies comparing medications adherence have become common yet they often do not account for differences in relative follow-up. Patient selection criteria may impact validity and comparability of these studies as well. METHODS: Adults with non-valvular atrial fibrillation, ≥1 rivaroxaban or apixaban dispensing (index date), and ≥1 year of pre-index eligibility were selected from IMS Health Real World Data Adjudicated Claims (IMS RWD Adjudicated Claims) and Truven Health MarketScan Research (Truven MarketScan) databases...
June 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28346965/point-of-care-coagulation-tests-monitoring-of-direct-oral-anticoagulants-and-their-reversal-therapy-state-of-the-art
#12
Giacomo E Iapichino, Paolo Bianchi, Marco Ranucci, Ekaterina Baryshnikova
Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations...
March 27, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28314985/the-role-of-new-oral-anticoagulants-in-orthopaedics-an-update-of-recent-evidence
#13
REVIEW
Dimitrios V Papadopoulos, Ioannis Kostas-Agnantis, Ioannis Gkiatas, Andreas G Tsantes, Panagiota Ziara, Anastasios V Korompilias
Rivaroxaban, dabigatran, apixaban and edoxaban are the four available new oral anticoagulants (NOAC) which are currently approved for venous thromboembolism prophylaxis after total hip and knee replacement. Large phase 3 and phase 4 studies comparing NOAC with low molecular weight heparins have shown similar results regarding the efficacy and safety of these two categories of anticoagulants. Management of bleeding complications is a matter of great significance. Three reversal agents have been developed: idarucizumab, andexanet alfa and ciraparantag...
March 17, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/28239301/the-reversal-effect-of-prothrombin-complex-concentrate-pcc-activated-pcc-and-recombinant-activated-factor-vii-against-anticoagulation-of-xa-inhibitor
#14
Nina Haagenrud Schultz, Hoa Thi Tuyet Tran, Stine Bjørnsen, Carola Elisabeth Henriksson, Per Morten Sandset, Pål Andre Holme
BACKGROUND: An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28210454/managing-patients-taking-edoxaban-in-dentistry
#15
REVIEW
Adrian Curto, Daniel Curto, Jorge Sanchez
BACKGROUND: Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28208197/reversal-of-direct-oral-anticoagulants-current-status-and-future-directions
#16
Jeffrey I Weitz
Direct oral anticoagulants (DOACs) are increasingly used for prevention and treatment of venous thromboembolism and for prevention of stroke in patients with nonvalvular atrial fibrillation. In phase III clinical trials that included more than 100,000 patients, the DOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with less serious bleeding, particularly less intracranial bleeding. Real-world evidence supports these outcomes. Despite this, some physicians and patients are concerned about serious bleeding or emergencies unless specific reversal agents for the DOACs are available...
February 2017: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#17
Sarah Monagle, John W Eikelboom, Kuan H Ng, Vinai C Bhagirath
Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed. We review the evidence for currently used and emerging reversal strategies, and discuss possible clinical implications, including increased prescription of DOACs, use of DOACs in clinical situations previously felt to pose too great a risk of bleeding, and use of reversal agents beyond currently approved indications...
March 2017: Future Cardiology
https://www.readbyqxmd.com/read/28191610/italian-intersociety-consensus-on-doac-use-in-internal-medicine
#18
Domenico Prisco, Walter Ageno, Cecilia Becattini, Armando D'Angelo, Giovanni Davì, Raimondo De Cristofaro, Francesco Dentali, Giovanni Di Minno, Anna Falanga, Gualberto Gussoni, Luca Masotti, Gualtiero Palareti, Pasquale Pignatelli, Roberto M Santi, Francesca Santilli, Mauro Silingardi, Antonella Tufano, Francesco Violi
The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events...
February 13, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28062209/thromboelastogram-does-not-detect-pre-injury-anticoagulation-in-acute-trauma-patients
#19
Jawad T Ali, Mitchell J Daley, Nina Vadiei, Zachary Enright, Joseph Nguyen, Sadia Ali, Jayson D Aydelotte, Pedro G Teixeira, Thomas B Coopwood, Carlos Vr Brown
PURPOSE: Thromboelastography (TEG) has been recommended to characterize post-traumatic coagulopathy, yet no study has evaluated the impact of pre-injury anticoagulation (AC) on TEG variables. We hypothesized patients on pre-injury AC have a greater incidence of coagulopathy on TEG compared to those without AC. METHODS: This retrospective chart review evaluated all trauma patients admitted to an urban, level one trauma center from February 2011 to September 2014 who received a TEG within the first 24h...
April 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28053220/application-of-static-modeling-in-the-prediction-of-in-vivo-drug-drug-interactions-between-rivaroxaban-and-anti-arrhythmic-agents-based-on-in-vitro-inhibition-studies
#20
Eleanor Jing Yi Cheong, Janice Jia Ni Goh, Yanjun Hong, Gopalakrishnan Venkatesan, Yuanjie Liu, Gigi Ngar Chee Chiu, Pipin Kojodjojo, Eric Chun Yong Chan
Rivaroxaban, a direct Factor Xa inhibitor, is indicated for stroke prevention in non-valvular atrial fibrillation (AF). Studies have revealed that the clearance of rivaroxaban is largely attributed to CYP3A4, CYP2J2 metabolism and P-gp efflux pathways. Amiodarone and dronedarone are anti-arrhythmic agents employed in AF management. Amiodarone, dronedarone and their major metabolites, N-desethylamiodarone (NDEA) and N-desbutyldronedarone (NDBD) demonstrate inhibitory effects on CYP3A4 and CYP2J2 with FDA recommended probe substrates...
January 4, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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