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Target-specific anticoagulant

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https://www.readbyqxmd.com/read/27933554/use-of-anticoagulant-rodenticides-by-pest-management-professionals-in-massachusetts-usa
#1
Kristin Memmott, Maureen Murray, Allen Rutberg
Secondary exposure to chemical rodenticides, specifically second-generation anticoagulant rodenticides (SGARs), poses a threat to non-target wildlife including birds of prey. Federal regulations in the United States currently limit homeowner access to SGARs as a way of minimizing this threat. With legal access to SGARs, pest management professionals (PMPs) represent a potential linkage to non-target exposure. There is limited research focused on rodent control practices, chemical rodenticide preferences, level of concern and awareness, or opinions on rodenticide regulations as they relate to PMPs...
December 8, 2016: Ecotoxicology
https://www.readbyqxmd.com/read/27920714/idarucizumab-as-antidote-to-intracerebral-hemorrhage-under-treatment-with-dabigatran
#2
Valentin Held, Philipp Eisele, Christoph C Eschenfelder, Kristina Szabo
BACKGROUND AND PURPOSE: Non-vitamin K anticoagulants (NOAC) such as dabigatran have become important therapeutic options for the prevention of stroke. Until recently, there were only nonspecific agents to reverse their anticoagulant effects in a case of emergency. Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited. METHODS: We report two cases of patients on dabigatran with acute intracerebral hemorrhage who received idarucizumab...
September 2016: Case Reports in Neurology
https://www.readbyqxmd.com/read/27918545/warfarin-traps-human-vitamin-k-epoxide-reductase-in-an-intermediate-state-during-electron-transfer
#3
Guomin Shen, Weidong Cui, Hao Zhang, Fengbo Zhou, Wei Huang, Qian Liu, Yihu Yang, Shuang Li, Gregory R Bowman, J Evan Sadler, Michael L Gross, Weikai Li
Although warfarin is the most widely used anticoagulant worldwide, the mechanism by which warfarin inhibits its target, human vitamin K epoxide reductase (hVKOR), remains unclear. Here we show that warfarin blocks a dynamic electron-transfer process in hVKOR. A major fraction of cellular hVKOR is in an intermediate redox state containing a Cys51-Cys132 disulfide, a characteristic accommodated by a four-transmembrane-helix structure of hVKOR. Warfarin selectively inhibits this major cellular form of hVKOR, whereas disruption of the Cys51-Cys132 disulfide impairs warfarin binding and causes warfarin resistance...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27906452/primary-prophylaxis-for-venous-thromboembolism-in-ambulatory-cancer-patients-receiving-chemotherapy
#4
REVIEW
Marcello Di Nisio, Ettore Porreca, Matteo Candeloro, Michele De Tursi, Ilaria Russi, Anne Ws Rutjes
BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27899064/gdf5-mediated-enhancement-of-chondrocyte-phenotype-is-inhibited-by-heparin-implication-for-the-use-of-heparin-in-the-clinic-and-in-tissue-engineering-applications
#5
Bethanie Imogen Ayerst, Raymond A A Smith, Victor Nurcombe, Anthony J Day, Catherine L R Merry, Simon Cool
The highly sulfated glycosaminoglycan (GAG) heparin is widely used in the clinic as an anticoagulant, and researchers are now using it to enhance stem cell expansion/ differentiation protocols, as well as to improve the delivery of growth factors for tissue engineering strategies. Growth differentiation factor 5 (GDF5) belongs to the bone morphogenetic protein family of proteins and is vital for skeletal formation, however, its interaction with heparin and heparan sulfate (HS) has not been studied. We identify GDF5 as a novel heparin/ HS-binding protein, and show that HS proteoglycans are vital in localizing GDF5 to the cell surface...
November 29, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27895055/role-of-agents-for-reversing-the-effects-of-target-specific-oral-anticoagulants
#6
REVIEW
Tanya R Riley, Mary L Gauthier-Lewis, Chelsea K Sanchez, Janine S Douglas
PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results...
November 28, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27857895/angiotensin-converting-enzyme-insertion-deletion-polymorphism-is-not-associated-with-vasoocclusive-complications-of-sickle-cell-anemia
#7
Sana Abass Mahjoub, Enaam Abdelrhman, Mohammed Elfatih Mohy El-Deen, Mustafa Sharf Eldin Mustafa, Elshazali Widaa Ali
CONTEXT: Sickle cell anemia (SCA) is a group of hemoglobin disorders in which the sickle β-globin gene is inherited. It is associated with many complications; most of them are related to thrombotic events. AIM: This study aimed to investigate the association between angiotensin converting enzyme (ACE) insertion/deletion polymorphism and complications of SCA. SETTINGS AND DESIGN: A case-control study was conducted in Khartoum state. SUBJECTS AND METHODS: A total of 50 patients with SCA and 40 healthy volunteers as a control group were enrolled in this study...
October 2016: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/27855643/evaluation-of-a-pharmacogenetic-based-warfarin-dosing-algorithm-in-patients-with-low-time-in-therapeutic-range-study-protocol-for-a-randomized-controlled-trial
#8
Leiliane Rodrigues Marcatto, Luciana Sacilotto, Carolina Tosin Bueno, Mirella Facin, Celia Maria Cassaro Strunz, Francisco Carlos Costa Darrieux, Maurício Ibrahim Scanavacca, Jose Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Junior Lima Santos
BACKGROUND: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital...
November 17, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27851137/1501-effect-of-target-specific-oral-anticoagulants-on-mortality-in-traumatic-brain-injury
#9
Jason Hecht, Madelyn Batey, Cherise Callahan
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27832552/current-limitations-of-the-assessment-of-haemostasis-in-adult-extracorporeal-membrane-oxygenation-patients-and-the-role-of-point-of-care-testing
#10
K Venkatesh, P S Nair, D J Hoechter, H Buscher
Haemostatic perturbations are commonly seen in extracorporeal membrane oxygenation (ECMO) patients and remain a clinical challenge, contributing significantly to morbidity and mortality. The approach to anticoagulation monitoring and the management of bleeding varies considerably across ECMO centres. Routine laboratory tests have their limitations in terms of turnaround time and specificity of information provided. Newer point-of-care testing (POCT) for coagulation may overcome these issues, as it provides information about the entire coagulation pathway from clot initiation to lysis...
November 2016: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/27816341/stroke-prevention
#11
Clothilde Isabel, David Calvet, Jean-Louis Mas
Patients who have had a stroke are at high risk for recurrent stroke, myocardial infarction, and vascular death. Prevention of these events should be initiated promptly after stroke, because many recurrent events occur early, and should be tailored to the precise cause of stroke, which may require specific treatment. Lifestyle advice including abstinence from smoking, regular exercise, Mediterranean-style diet, and reduction of salt intake and alcohol consumption are recommended for all patients with stroke...
December 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27789479/design-and-characterization-of-an-apc-specific-serpin-for-the-treatment-of-hemophilia
#12
Stéphanie G I Polderdijk, Ty E Adams, Lacramioara Ivanciu, Rodney M Camire, Trevor P Baglin, James A Huntington
Hemophilia is a bleeding disorder caused by deficiency in factors VIII or IX, the two components of the intrinsic Xase complex. Treatment with replacement factor can lead to the development of inhibitory antibodies, requiring the use of bypassing agents such as factor VIIa and factor concentrates. An alternative approach to bypass the Xase complex is to inhibit endogenous anticoagulant activities. Activated protein C (APC) breaks down the complex that produces thrombin by proteolytically inactivating factor Va...
October 27, 2016: Blood
https://www.readbyqxmd.com/read/27765678/effect-of-anticoagulants-on-the-protein-corona-induced-reduced-drug-carrier-adhesion-efficiency-in-human-blood-flows
#13
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
https://www.readbyqxmd.com/read/27757787/identification-of-risk-factors-for-inappropriate-and-suboptimal-initiation-of-direct-oral-anticoagulants
#14
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
https://www.readbyqxmd.com/read/27752630/admission-rates-for-emergency-department-patients-with-venous-thromboembolism-and-estimation-of-the-proportion-of-low-risk-pulmonary-embolism-patients-a-us-perspective
#15
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: Clinical and Experimental Emergency Medicine
https://www.readbyqxmd.com/read/27725023/correlation-between-rivaroxaban-xarelto-plasma-activity-patient-clinical-variables-and-outcomes-in-a-south-african-centre
#16
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
https://www.readbyqxmd.com/read/27705927/heparan-sulfate-hexasaccharide-selectively-inhibits-cancer-stem-cells-self-renewal-by-activating-p38-map-kinase
#17
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
https://www.readbyqxmd.com/read/27702402/development-of-antithrombotic-aptamers-from-recognizing-elements-to-drugs
#18
Elena Zavyalova, Andrey Golovin, Galina Pavlova, Alexey Kopylov
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...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27697436/evidence-supporting-idarucizumab-for-the-reversal-of-dabigatran
#19
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
https://www.readbyqxmd.com/read/27696935/the-evolution-of-recombinant-thrombolytics-current-status-and-future-directions
#20
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
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