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oral direct thrombin inhibitors

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https://www.readbyqxmd.com/read/29325495/management-of-cancer-associated-venous-thromboembolism-a-case-based-practical-approach
#1
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/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
#2
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/29295790/direct-oral-anticoagulants-an-update
#3
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/29242919/association-of-novel-oral-antithrombotics-with-the-risk-of-intraocular-bleeding
#4
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
#5
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/29199435/-laboratory-aspects-of-novel-oral-anticoagulant-treatment
#6
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
#7
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/29176379/thrombin-generation-estimates-the-anticoagulation-effect-of-direct-oral-anticoagulants-with-significant-interindividual-variability-observed
#8
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
#9
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/29126301/coagulation-testing-in-the-core-laboratory
#10
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29117605/-new-oral-anticoagulants-noac-in-stroke-treatment
#11
Clemens Küpper, Lars Kellert, Steffen Tiedt, Frank Arne Wollenweber
Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only...
November 8, 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29105079/direct-oral-anticoagulants-versus-warfarin-for-preventing-stroke-and-systemic-embolic-events-among-atrial-fibrillation-patients-with-chronic-kidney-disease
#12
REVIEW
Miho Kimachi, Toshi A Furukawa, Kimihiko Kimachi, Yoshihito Goto, Shingo Fukuma, Shunichi Fukuhara
BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin...
November 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29072911/the-design-of-small-molecule-active-site-inhibitors-of-the-s1a-family-proteases-as-procoagulant-and-anticoagulant-drugs
#13
Peter M Fischer
Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose-response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains...
October 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29053656/is-it-necessary-to-alter-anticoagulation-therapy-for-tooth-extraction-in-patients-taking-direct-oral-anticoagulants
#14
M Caliskan, H-C Tükel, M-E Benlidayi, A Deniz
BACKGROUND: The number of patients using direct oral anticoagulants (DOACs) instead of vitamin K antagonists (VKA) is increasing and there is limited data on the safety of tooth extractions in patients taking DOACs. The aim of this study was to compare the amount of bleeding (AOB) and postoperative complications after tooth extractions between patients taking VKAs and patients taking DOACs without altering the anticoaguation therapy. MATERIAL AND METHODS: The study consisted of four groups: Direct thrombin inhibitor group, factor Xa inhibitor group, warfarin group and a control group...
November 1, 2017: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/29050502/first-evidence-trap-induced-platelet-aggregation-is-reduced-in-patients-receiving-xabans
#15
Frantisek Nehaj, Juraj Sokol, Jela Ivankova, Michal Mokan, Frantisek Kovar, Jan Stasko, Marian Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28979172/reversing-factor-xa-inhibitors-clinical-utility-of-andexanet-alfa
#16
REVIEW
Scott Kaatz, Hardik Bhansali, Joseph Gibbs, Robert Lavender, Charles E Mahan, David G Paje
Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28952381/discovery-methods-of-coagulation-inhibiting-drugs
#17
Antonio Gómez-Outes, Minerva García-Fuentes, Mª Luisa Suárez-Gea
In the last decade, several direct oral anticoagulants (DOAC) targeting thrombin (dabigatran) or activated factor X (FXa) (rivaroxaban, apixaban and edoxaban) have been marketed for a number of indications related to prophylaxis and treatment of thrombotic diseases. All these drugs are effective in preventing thrombosis, but are associated with an increased bleeding risk. Areas covered: This review includes a summary of new targets for anticoagulation (e.g.: FXIa, FXIIa, protein disulfide isomerase, polyphosphates, etc...
September 27, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28930804/venous-thromboembolism-in-gynecological-malignancy
#18
Abigail Cohen, Chung Sim Lim, Alun Huw Davies
OBJECTIVE: Venous thromboembolism (VTE) is a recognized complication of gynecological malignancy and represents a leading cause of morbidity and mortality in these patients. The review aimed to discuss the incidence, risk factors, and clinical presentation of VTE before examining the literature on the diagnosis, prevention, and management in the context of uterine, cervical, ovarian, and vulval cancers. METHODS/MATERIALS: A literature search was performed using Ovid Medline and Embase with the following words: "gynecological malignancy," "pelvic tumor," "venous thromboembolism," "deep vein thrombosis" and "pulmonary embolism...
November 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28929298/chronic-kidney-disease-and-anticoagulation-from-vitamin-k-antagonists-and-heparins-to-direct-oral-anticoagulant-agents
#19
REVIEW
Savino Sciascia, Massimo Radin, Karen Schreiber, Roberta Fenoglio, Simone Baldovino, Dario Roccatello
Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)] are at high risk of bleeding events (both non-major and major clinically relevant bleeding). While anticoagulation reduces the risk of thromboembolic events, the co-existing bleeding risk and the fact that the most commonly used anticoagulation agents are eliminated via the kidneys pose additional challenges...
December 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28921890/phase-iia-study-of-dabigatran-etexilate-in-children-with-venous-thrombosis-pharmacokinetics-safety-and-tolerability
#20
J M L Halton, M Albisetti, B Biss, L Bomgaars, M Brueckmann, S Gropper, R Harper, F Huang, M Luciani, H Maas, I Tartakovsky, L G Mitchell
Essentials Dabigatran etexilate may provide a new treatment option for pediatric venous thromboembolism. Children aged 1 to < 12 years were given dabigatran etexilate in an open-label, single-arm study. The pharmacokinetic-pharmacodynamic relationship was similar to that seen in adult patients. There were no serious adverse events, bleeding events or recurrent venous thromboembolism. SUMMARY: Background The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
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