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Target-specific anticoagulant

Daniel J Sobczynski, Omolola Eniola-Adefeso
Plasma proteins rapidly coat the surfaces of particulate drug carriers to form a protein corona upon their injection into the bloodstream. The high presence of immunoglobulins in the corona formed on poly(lactic-co-glycolic acid) (PLGA) vascular-targeted carrier (VTC) surfaces was recently shown to negatively impact their adhesion to activated endothelial cells (aECs) in vitro. Here, we characterized the influence of anticoagulants, or their absence, on the binding efficiency of VTCs of various materials via modulation of their protein corona...
October 17, 2016: Acta Biomaterialia
Molly Howard, Andrew Lipshutz, Breanne Roess, Emily Hawes, Zachariah Deyo, Jena Ivey Burkhart, Stephan Moll, Betsy Bryant Shilliday
Direct Oral Anticoagulants (DOACs) require specific dosing and monitoring to ensure safe and appropriate use. The purpose of this evaluation was to identify patient- and process-related factors that correlate with increased risk of inappropriate prescribing of DOACs. A retrospective chart review was conducted in three outpatient clinics within an academic medical center to identify patients started on DOAC therapy and evaluate the appropriateness of DOAC initiation. Data collected included patient demographics, DOAC medication initiated, dose, indication, baseline laboratory values, concomitant medications, type and specialty of prescriber, and initiation setting...
October 18, 2016: Journal of Thrombosis and Thrombolysis
Adam J Singer, Henry C Thode, W Frank Peacock
OBJECTIVE: Introduction of target specific anticoagulants and recent guidelines encourage outpatient management of low risk patients with venous thromboembolism. We describe hospital admission rates over time for patients presenting to US emergency departments (EDs) with deep vein thrombosis (DVT) and pulmonary embolism (PE) and estimate the proportion of low-risk PE patients who could potentially be managed as outpatients. METHODS: We performed a structured analysis of the National Hospital Ambulatory Medical Care Survey (a nationally representative weighted sampling of US ED visits) database for the years 2006-2010 including all adult patients with a primary diagnosis of DVT or PE...
September 2016: Clin Exp Emerg Med
S Louw, N P Saragas, P N Ferrao, T F Chirwa, B F Jacobson
BACKGROUND: Low-molecular-weight heparin and vitamin K antagonists such as warfarin are the gold standard for prohylaxis and treatment of venous thromboembolic disease (VTED). Direct oral anticoagulants (DOACs) result in predictable anticoagulation with significantly reduced inter- and intra-patient variability. DOAC absorption is rapid, with a short half-life and relatively few drug interactions. DOACs are effective and safe at fixed doses without activity monitoring. However, specific situations may require assessment of accurate drug activity...
September 8, 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Nirmita J Patel, Chetna Sharon, Somesh Baranwal, Rio S Boothello, Umesh R Desai, Bhaumik B Patel
Heparan sulfate (HS) plays a role in the majority of essential hallmarks of cancer, yet its ability to modulate self-renewal, especially of cancer stem cells (CSCs), remains unknown. We have discovered that a non-anticoagulant HS hexasaccharide (HS06) sequence, but not other shorter or longer sequences, selectively inhibited CSC self-renewal and induced apoptosis in colorectal, pancreatic, and breast CSCs suggesting a very general phenomenon. HS06 inhibition of CSCs relied upon early and sustained activation of p38α/β mitogen activated protein kinase (MAPK) but not other MAPKs family members i...
September 30, 2016: Oncotarget
Zavyalova Elena, Golovin Andrey, Pavlova Galina, Kopylov Alexey
Blood hemostasis is attained with two sophisticated interconnected network systems, a coagulation cascade and a platelet activation system. Multiple inhibitors were developed to various components of both systems to prevent thrombosis-related morbid events that are of extremely high frequency in the human population. Antithrombotic inhibitors possess both positive and negative aspects. One of the essential modern requirements is a controllable mode of action for both anticoagulants and antiplatelets that could be achieved due to the high affinity and specificity of the inhibitor, as well as a possibility to apply an antidote, which quickly annihilates activity of the inhibitor and restores the proper hemostasis...
October 4, 2016: Current Pharmaceutical Design
Charles V Pollack
Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant effects of dabigatran in animal studies and phase 1 studies of young, elderly, and renally impaired volunteers. Although elective invasive procedures and most bleeding complications in dabigatran-treated patients can be managed by temporarily stopping dabigatran therapy and using supportive measures, there are rare clinical situations that require urgent reversal of the anticoagulant effect of dabigatran...
September 28, 2016: American Journal of Emergency Medicine
Yogender Pal Khasa
Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem...
October 3, 2016: Bioengineered
Dominique Stephan, Elena-Mihaela Cordeanu, Corina Mirea, Alix Faller, Anne Lejay, Sébastien Gaertner
Non-vitamin K antagonist oral anticoagulants are becoming increasingly important in the prophylaxis and treatment of thrombosis in atrial fibrillation and venous thromboembolism. Antiplatelets are widely prescribed in the primary and secondary prevention of cardiac and vascular diseases. There are potentially numerous situations where anticoagulants and antiplatelets may be combined; these combinations have been explored in coronary artery disease, and some have been included in updated recommendations. Is it legitimate to transpose these recommendations to the management of peripheral artery disease? The specific characteristics of the treated vessels, the stents used, the respective frequencies of stent thrombosis and its effect on the target organ are probably different, and explain why opinions differ...
September 28, 2016: Archives of Cardiovascular Diseases
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
In the past decade Direct Oral Anti-Coagulants (DOACs), targeting Thrombin or Factor Xa, have enormously facilitated the daily treatment of all relevant patients, including those requiring lifelong therapy. These DOACs have considerable advantages over the use of oral Vitamin K Antagonist (VKA) treatments, in view of having little interferences with food and other medications and also not requiring adjustment for age, gender or weight, with some well-defined exceptions. In this current What's Happening Section we focus on measurements of DiXaIs in plasma using anti-Xa assays, with the objective of providing a tribute to Professor Michel Meyer Samama, who was not only a real leader in this field but, in the past, both authors benefited from his wisdom, as a teacher who dedicated his scientific and professional life (among many other interests in hemostasis, thrombosis and fibrinolysis) to develop and promote methods and strategies for laboratory monitoring of anticoagulants...
October 2016: Transfusion and Apheresis Science
Benilde Cosmi
Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs. Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes...
October 12, 2016: Expert Opinion on Pharmacotherapy
Jinhua Zhang, Lihong Tian, Jinlong Huang, Sihan Huang, Tingting Chai, Jianzhen Shen
AIM: To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement. METHODS: A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager Version 5...
September 23, 2016: Cardiovascular Therapeutics
Jaime Masjuan, Alicia DeFelipe
Patients with atrial fibrillation and prior stroke or transient ischemic attack exhibit a very high risk of recurrence. Secondary prevention with oral anticoagulants is mandatory. Overall, clinical guidelines recommend the use of target-specific oral anticoagulants over vitamin K antagonists for secondary prevention of stroke in patients with atrial fibrillation. However, many patients with atrial fibrillation and previous stroke are not receiving the appropriate antithrombotic treatment, perhaps due to the perceived risks of anticoagulation including the risk of hemorrhagic transformation of an ischemic stroke...
September 20, 2016: International Journal of Neuroscience
N Krzyżaniak, I Pawłowska, B Bajorek
WHAT IS KNOWN AND OBJECTIVES: When considering acute care settings, such as the neonatal intensive care unit (NICU), the inappropriate use of medicines poses a great risk to vulnerable babies at the start of their lives. However, there is limited published literature that explores the current medication management practices in NICUs and where the main misuse issues lie. Therefore, the purpose of this review was to give an overview of medicine use in NICUs worldwide and identify therapeutic areas requiring more targeted pharmaceutical care...
August 31, 2016: Journal of Clinical Pharmacy and Therapeutics
Charles V Pollack
Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant effects of dabigatran in animal studies and phase 1 studies of young, elderly, and renally impaired volunteers. Although elective invasive procedures and most bleeding complications in dabigatran-treated patients can be managed by temporarily stopping dabigatran therapy and using supportive measures, there are rare clinical situations that require urgent reversal of the anticoagulant effect of dabigatran...
November 2016: American Journal of Medicine
Katherine V Hurst, John Matthew O'Callaghan, Ashok Handa
The new generation of target-specific oral anticoagulants is being prescribed for increasing numbers of patients at risk of stroke or venous thromboembolism (VTE). These drugs offer valuable benefits due to fast onset anticoagulation, a fixed anticoagulation effect (allowing administration of specified doses), and no requirement for routine monitoring. Edoxaban is a fast-acting oral anticoagulant, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and in the treatment of acute VTE...
2016: Vascular Health and Risk Management
Vallerinteavide Mavelli Girish, R Manjunatha Kini
Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin...
2016: Scientific Reports
Zhao Jing, Weiqiang Fei, Jichun Zhou, Lumin Zhang, Liuxi Chen, Xiaomin Zhang, Xiao Liang, Jiansheng Xie, Yong Fang, Xinbing Sui, Weidong Han, Hongming Pan
Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines...
August 19, 2016: Oncotarget
Brendan P McDonnell, Kate Glennon, Aoife McTiernan, Hugh D O'Connor, Colin Kirkham, Barry Kevane, Jennifer C Donnelly, Fionnuala Ni Áinle
Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality in the developed world. Low molecular weight heparins (LMWH) are routinely used to provide therapeutic anticoagulation during pregnancy for women with VTE, with measurement of plasma anti-FXa activity used to guide dosing in certain patient groups. There is limited evidence to support the use of anti-FXa monitoring in pregnant patients. This study seeks to ascertain whether anti-FXa monitoring of pregnant patients with VTE influences patient outcomes...
August 12, 2016: Journal of Thrombosis and Thrombolysis
Rebecca Lawton, Jane Heyhoe, Gemma Louch, Emma Ingleson, Liz Glidewell, Thomas A Willis, Rosemary R C McEachan, Robbie Foy
BACKGROUND: There are recognised gaps between evidence and practice in general practice, a setting posing particular implementation challenges. We earlier screened clinical guideline recommendations to derive a set of 'high-impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. Here, we explore health professionals' perceived determinants of adherence to these indicators, examining the degree to which determinants were indicator-specific or potentially generalisable across indicators...
2016: Implementation Science: IS
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