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Novel anticoagulants

So-Young Kim, Drew R Jones, Ji-Yeon Kang, Chul-Ho Yun, Grover P Miller
Coumadin (R/S-warfarin) metabolism plays a critical role in patient response to anticoagulant therapy. Several cytochrome P450s oxidize warfarin into R/S-6-, 7-, 8-, 10, and 4'-hydroxywarfarin that can undergo subsequent glucuronidation by UDP-glucuronosyltransferases (UGTs); however, current studies on recombinant UGTs cannot be adequately extrapolated to microsomal glucuronidation capacities for the liver. Herein, we estimated the capacity of the average human liver to glucuronidate hydroxywarfarin and identified UGTs responsible for those metabolic reactions through inhibitor phenotyping...
March 15, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Mohammed Rashid Akhtar, Jimmy Kyaw Tun, Riad Alchanan, Ounali Jaffer, Snehal Patel, Joo-Young Chun, Nicholas Bunker, Tim Fotheringham
There has been increasing use of a novel combined femoral venous sheath, catheter and retrievable self-expanding and collapsible diamond-shaped IVC filter (Angel® Catheter, BiO2 Medical), in severely injured patients who cannot receive anticoagulation. As the filter is not detached from the catheter/sheath, it should be easily retrieved. Outcomes included in large registries demonstrate a high safety profile and a 100% retrieval rate. However, at our institution-a Level 1 major UK trauma centre with 4 years of substantial experience in using this device-we've encountered three cases of device fracture and subsequent complicated retrieval dating from Dec 2016 to March 2017...
March 14, 2018: Cardiovascular and Interventional Radiology
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
Kate M Richmond, Katharine G Warburton, Simon J Finney, Sachin Shah, Benjamin A J Reddi
INTRODUCTION: Comprehensive clinical examination can be compromised in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Adjunctive diagnostic imaging strategies range from bedside imaging only to routine computed tomography (CT). The risk-benefit of either approach remains to be evaluated. Patients retrieved to the Royal Brompton Hospital (RBH) on VV-ECMO routinely undergo admission CT imaging of head, chest, abdomen and pelvis. This study aimed to identify how frequently changes in therapy or adverse events could be attributed to routine CT scanning...
March 1, 2018: Perfusion
Tawseef Dar, Mohit K Turagam, Bharath Yarlagadda, Mohmad Tantary, Seth H Sheldon, Dhanunjaya Lakkireddy
Left atrial appendage closure (LAAC) has emerged as a viable option for stroke prevention, especially in those intolerant of or not suitable for long-term oral anticoagulation therapy. This article describes the clinical characteristics, indications, and a proposed referral system for potential LAAC patients. Patient selection remains a challenge because of the paradox between the available randomized data on this intervention and the actual patient population who may gain maximum benefit. Further investigations comparing different LAAC devices with each other and with novel oral anticoagulants are needed...
April 2018: Interventional Cardiology Clinics
Ikjae Lee, Hani Kushlaf
INTRODUCTION: The aim of this study was to evaluate needle electromyography (EMG) practice patterns among electromyographers in patients taking novel oral anticoagulants (NOACs). METHODS: A survey questionnaire was sent to members of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) via email weblink. Anonymous survey responses were collected through an online website. RESULTS: 58 AANEM members responded, 28 (48%) of whom worked at a teaching hospital and 30 (52%) in a private setting...
March 6, 2018: Muscle & Nerve
Chrisanna Dobrowolski, Doruk Erkan
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). At the present time, treatment is primarily focused on anticoagulation. However, there is increasing awareness of the mechanisms involved in APS pathogenesis, which has led to the trial of novel therapies targeting those mechanisms. Following a brief review of the etiopathogenesis of and current management strategies in APS, this paper focuses on the evidence for these potential, targeted APS treatments, e...
March 3, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Vinayak Nagaraja, Greg Cranney, Virag Kushwaha
In the prevention and treatment of thromboembolic disease, novel oral anticoagulants have emerged as alternatives to warfarin. A major challenge continues to be the reversal of their anticoagulant effect in the case of life-threatening haemorrhagic complications. We report a case of spontaneous splenic rupture treated by splenic artery embolisation in a 77-year-old woman who was anticoagulated with rivaroxaban.
March 5, 2018: BMJ Case Reports
Margaret Smith, Glenn Wakam, Thomas Wakefield, Andrea Obi
Anticoagulation pharmacy has been dramatically altered with US Food and Drug Administration (FDA) approval of 5 direct oral anticoagulants, 1 novel reversal agent and, a second designated for fast-track approval. Trial data surrounding current trends in anticoagulant choice for VTE, reversal, and bridging are constantly redefining practice. Extended therapy for unprovoked VTE has expanded to include low-dose direct oral anticoagulants, aspirin, and the use of the HERDOO2 system to identify women who can stop anticoagulant therapy without increased risk of recurrent VTE...
April 2018: Surgical Clinics of North America
Weronika Kotkowiak, Jolanta Lisowiec-Wachnicka, Jakub Grynda, Ryszard Kierzek, Jesper Wengel, Anna Pasternak
Thrombin is a serine protease that plays a crucial role in hemostasis, fibrinolysis, cell proliferation, and migration. Thrombin binding aptamer (TBA) is able to inhibit the activity of thrombin molecule via binding to its exosite I. This 15-nt DNA oligonucleotide forms an intramolecular, antiparallel G-quadruplex structure with a chair-like conformation. In this paper, we report on our investigations on the influence of certain modified nucleotide residues on thermodynamic stability, folding topology, and biological properties of TBA variants...
March 2, 2018: Molecular Therapy. Nucleic Acids
Kevin Fortier, Deepti Shroff, Uday N Reebye
BACKGROUND: Dabigatran, rivaroxaban, apixaban and edoxaban are approved novel oral anticoagulants (NOACs) as alternatives to Vitamin K antagonists (VKA). Physicians are prescribing an ever-increasing amount these drugs to their patients due to various advantages over existing medications. AIMS: The objective of this review is to provide the dental professional with current literature surrounding the emergence of NOACs, as well as various case studies on the subject, in an effort to guide clinical decision making regarding these medications...
February 28, 2018: Gerodontology
Tawseef Dar, Bharat Yarlagadda, James Vacek, Buddhadeb Dawn, Dhanunjaya Lakkireddy
Background: Bleeding complications especially gastrointestinal bleeding remains a major challenge associated with oral anticoagulation therapy (OAT) and often leads clinicians to withdraw oral anticoagulation therapy (OAT) . This exposes patients to risk of stroke and systemic thromboembolism (STE). Novel oral anticoagulants (NOACs) have proved no better when it comes to bleeding events and in fact studies have shown that overall NOACs are associated with higher incidence of gastrointestinal (GI) bleeding compared to warfarin ...
December 2017: Journal of Atrial Fibrillation
Hany S Abed, Michael J Kilborn, Vivien Chen, Raymond W Sy
The incidence and prevalence of atrial fibrillation (AF) is expected to more than double between 2010 and 2030. Accordingly, the use of non-vitamin K oral anticoagulant (NOAC) agents for thromboembolic stroke prevention is anticipated to increase. The development of effective and safe antidotes is needed to address the unmet need for rapid anticoagulation reversal. The immediate role for these novel antidotes is for reversal of NOAC activity in life threatening bleeding and urgent surgical intervention. In addition, reversal agents may play an important role in simplifying bridging protocols in the peri-procedural period for catheter ablation of AF and elective surgery...
December 2017: Journal of Atrial Fibrillation
Ali Khoynezhad
Stroke remains a major complication of atrial fibrillation and third leading cause of death in Western Countries. [1] While Coumadin and novel oral anticoagulants have been efficient in reducing the stoke risk in patients with atrial fibrillation; there is a subset of patients who are not candidates for anticoagulation.[2] The management of these patients is clinical challenge.We describe a patient with history of permanent atrial fibrillation with contra-indication to anticoagulation presenting with and left atrial thrombus...
December 2017: Journal of Atrial Fibrillation
Emily Guzman, Jeanmaire Molina
CONTEXT: Cardiovascular disease (CVD) is the number one cause of death globally, responsible for over 17 million (31%) deaths in the world. Novel pharmacological interventions may be needed given the high prevalence of CVD. OBJECTIVE: In this study, we aimed to find potential new sources of cardiovascular (CV) drugs from phylogenetic and pharmacological analyses of plant species that have experimental and traditional CV applications in the literature. MATERIALS AND METHODS: We reconstructed the molecular phylogeny of these plant species and mapped their pharmacological mechanisms of action on the phylogeny...
December 2018: Pharmaceutical Biology
Feineng Shang, Na Gao, Ronghua Yin, Lisha Lin, Chuang Xiao, Lutan Zhou, Zi Li, Steven W Purcell, Mingyi Wu, Jinhua Zhao
Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development...
February 15, 2018: European Journal of Medicinal Chemistry
Xuefeng Hu, Ying Xiao, Chuan Yu, Yinglin Zuo, Wen Yang, Xinan Wang, Baohua Gu, Jing Li
Factor Xa (FXa) is a serine protease that plays key roles in linking the intrinsic and extrinsic coagulation pathways to the final common pathway. DJT06001 is an oral, highly specific and direct FXa inhibitor for the prevention and treatment of thromboembolic diseases. We characterized the compound in vitro and studied its in vivo activity in rat thrombosis models, as well as bleeding risk and Pharmacokinetics and Pharmacodynamics (PK/PD) relationship. DJT06001 inhibited free FXa with an inhibitory constant (Ki) of 0...
February 21, 2018: European Journal of Pharmacology
Edward F Plow, Yunmei Wang, Daniel I Simon
Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis...
February 21, 2018: Blood
Rui Wu, Yiwei Kong, Jianyong Yin, Rulian Liang, Zeyuan Lu, Niansong Wang, Qing Zhao, Yang Zhou, Chungen Yan, Feng Wang, Mingyu Liang
BACKGROUND/AIMS: Antithrombin Ⅲ (AT Ⅲ) is an important endogenous anticoagulant and has strong anti-inflammatory properties. Low ATⅢ activity is considered to be a predictor of poor outcomes in several conditions, including acute kidney injury after cardiac surgery. However, the association between the ATⅢ level and the occurrence of contrast induced nephropathy (CIN) has not been elucidated. In this study, our aim was to identify the potential predictive value of ATⅢ for CIN...
February 16, 2018: Kidney & Blood Pressure Research
Lu Yang, Arup Bhattacharya, Yun Li, Yuesheng Zhang
We recently discovered a plasma proteolysis pathway, termed the FXII-FVII pathway which is composed of coagulation proteases, and found it to be mainly responsible for the clearance of Aβ42 in the plasma in mice. Aβ42 and Aβ40 are the main Aβ forms in Alzheimer's disease (AD). In the present study, in vitro assays, wild type (WT) mice and J20 mice (a transgenic AD model) are used to assess the degradation of Aβ40 and Aβ42 by the FXII-FVII pathway and the impact of anticoagulants on such degradation. Four clinically available and mechanistically distinct anticoagulants are evaluated, including dabigatran, enoxaparin (EP), rivaroxaban and warfarin...
January 19, 2018: Oncotarget
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