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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/29321328/activities-of-thrombin-and-factor-xa-are-essential-for-replication-of-hepatitis-e-virus-and-are-possibly-implicated-in-the-orf1-polyprotein-processing
#2
Gayatri D Kanade, Kunal D Pingale, Yogesh A Karpe
Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The ORF1 of HEV encodes a non-structural polyprotein of 1693 amino acids. It is not clear whether the ORF1 polyprotein is processed into distinct enzymatic domains. Many researchers have attempted to understand the mechanisms of pORF1 processing. However, these studies gave varied results and could never convincingly establish the mechanism of pORF1 processing. In this study, we demonstrated the possible role of thrombin and factor Xa in pORF1 processing...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29319249/stroke-prevention-in-atrial-fibrillation-which-is-the-best-balanced-in-efficacy-and-safety-as-a-thromboprophylactic
#3
Viraj Suvarna
Stroke prevention in atrial fibrillation (AF) has reached an exciting phase with a plethora of newer, potentially more efficacious and safer agents being introduced for physicians to select from. Dabigatran belongs to a class of anticoagulants called direct thrombin inhibitors, while rivaroxaban, apixaban, and edoxaban are direct Factor Xa inhibitors. Purely from a therapeutic endpoint perspective-based on the action of anticoagulants in reducing cardioembolic stroke-in clinical trials, one should look at whether a new anticoagulant in patients with AF prevents ischemic stroke...
October 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29314216/association-of-prothrombin-complex-concentrates-administration-and-hematoma-enlargement-in-noac-related-intracerebral-hemorrhage
#4
Stefan T Gerner, Joji B Kuramatsu, Jochen A Sembill, Maximilian I Sprügel, Matthias Endres, Karl Georg Haeusler, Peter Vajkoczy, Peter A Ringleb, Jan Purrucker, Timolaos Rizos, Frank Erbguth, Peter D Schellinger, Gereon R Fink, Henning Stetefeld, Hauke Schneider, Hermann Neugebauer, Joachim Röther, Joseph Claßen, Dominik Michalski, Arnd Dörfler, Stefan Schwab, Hagen B Huttner
OBJECTIVE: To investigate parameters associated with hematoma enlargement in non-vitamin-K-antagonist-anticoagulant(NOAC)-related intracerebral hemorrhage(ICH). METHODS: Retrospective cohort study including individual patient data of 190 patients with NOAC-associated ICH over a 5-year-period(2011-2015) at 19 Departments of Neurology across Germany. Primary outcome was the association of PCC-administration with hematoma enlargement. Subanalyses were calculated for blood-pressure management and its association with the primary outcome...
January 3, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29304537/clinical-impact-and-course-of-anticoagulant-related-major-bleeding-in-cancer-patients
#5
Noémie Kraaijpoel, Nick van Es, Suzanne M Bleker, Marjolein P A Brekelmans, Elise S Eerenberg, Saskia Middeldorp, Alexander T Cohen, Gary E Raskob, Harry R Büller
Cancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29304529/passivating-injured-endothelium-with-kinexins-in-thrombolytic-therapy
#6
Yunn-Hwa Ma, Chao-Wei Huang, Chih-Jen Wen, Yi-Ching Lu, Shiaw-Pyng Wey, Tze-Chein Wun
Without conjunctive administration of an anticoagulant, endothelial injury-induced thrombosis is resistant to thrombolysis and prone to re-thrombosis. We hypothesized that co-delivery of recombinant tissue plasminogen activator (rtPA) with annexin V-containing anticoagulants that specifically target the injured endothelium may passivate the thrombogenic elements of the vascular injury site and enhance rtPA-induced thrombolysis. In this study, the effects of conjunctive administration of Kinexins (Kunitz inhibitor-annexin V fusion proteins) with rtPA on thrombolysis were determined in vitro and in vivo...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29302946/the-role-of-protein-z-and-protein-z-dependent-protease-inhibitor-polymorphisms-in-the-development-of-prosthetic-heart-valve-thrombosis
#7
Süleyman Karakoyun, Mustafa Ozan Gürsoy, Macit Kalçık, Mahmut Yesin, Sabahattin Gündüz, Mehmet Ali Astarcıoğlu, Zübeyde Bayram, Beytullah Çakal, Emrah Bayam, Mehmet Özkan
BACKGROUND: Protein Z (PZ) is a vitamin K-dependent factor that is synthesized mainly by the liver. It acts as an activator of serpin, the protein Z-dependent inhibitor (ZPI), which inhibits factor Xa. The potential role of alterations in protein Z and/or ZPI levels in the pathogenesis of thrombotic and/or hemorrhagic diseases has been previously investigated, but results have been conflicting. The study aim was to evaluate the role of PZ/ZPI polymorphisms in the development of prosthetic valve thrombosis (PVT)...
July 2017: Journal of Heart Valve Disease
https://www.readbyqxmd.com/read/29297662/venous-thromboembolism-role-of-pharmacists-and-managed-care-considerations
#8
Tuesdy Horner, Charles E Mahan
Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Anticoagulation is used in patients with VTE to reduce the risk of recurrent VTE and VTE-related death. The overall incidence of VTE is 1 to 2 per 1000 person-years. Long-term mortality for patients with VTE is poor, with 25% of patients not surviving 7 days and nearly 40% not surviving the first year. Coagulation disorders demand effective anticoagulant therapy to avoid complications, especially recurrent VTE and VTE-related death...
December 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/29296829/safety-pharmacokinetics-and-reversal-of-apixaban-anticoagulation-with-andexanet-alfa
#9
Deborah Siegal, Genmin Lu, Janet M Leeds, Mark Karbarz, Janice Castillo, Vandana Mathur, Athiwat Hutchaleelaha, Uma Sinha, Michael Kitt, Matt McClure, Stanley J Hollenbach, John T Curnutte, Pamela B Conley, Mark Crowther
Direct factor Xa (FXa) inhibitors lack a specific reversal agent for emergencies such as major bleeding or urgent surgery. Andexanet alfa, a modified, catalytically inactive, recombinant human FXa derivative, reverses anticoagulant effect by binding and sequestering FXa inhibitors. This original report of safety and dose-finding, phase 1 and 2 randomized, double-blind, placebo-controlled studies, investigated various doses of andexanet in healthy volunteers. Phase 1 evaluated the safety and pharmacokinetics of andexanet (n = 24) or placebo (n = 8)...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295790/direct-oral-anticoagulants-an-update
#10
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/29291252/tfpi%C3%AE-interacts-with-fva-and-fxa-to-inhibit-prothrombinase-during-the-initiation-of-coagulation
#11
Jeremy P Wood, Helle H Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E Mast
Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29287144/enhanced-biopharmaceutical-performance-of-rivaroxaban-through-polymeric-amorphous-solid-dispersion
#12
Sunita Metre, Sumit Mukesh, Sanjaya K Samal, Mahesh Chand, Abhay T Sangamwar
Rivaroxaban (RXB) is an orally active direct inhibitor of the activated serine protease Factor Xa, given as monotherapy in the treatment of venous thromboembolism (VTE). It has been characterized in-vitro as a substrate for the active, non-saturable efflux via P-gp transporter, limiting its high permeability. Therefore, role of P-gp inhibiting polymers in enhancing the biopharmaceutical performance of RXB by preparing polymeric amorphous solid dispersion and subsequent improvement in solubility and permeability was investigated...
December 29, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29285431/acute-kidney-injury-aggravated-by-treatment-initiation-with-apixaban-another-twist-of-anticoagulant-related-nephropathy
#13
Sergey V Brodsky, Nilesh S Mhaskar, Sampath Thiruveedi, Rajnish Dhingra, Sharon C Reuben, Edward Calomeni, Iouri Ivanov, Anjali Satoskar, Jessica Hemminger, Gyongyi Nadasdy, Lee Hebert, Brad Rovin, Tibor Nadasdy
Anticoagulant-related nephropathy (ARN) was initially described in patients on warfarin (as warfarin-related nephropathy) and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis). Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI). A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts...
December 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/29284351/recurrence-of-malignancy-associated-venous-thromboembolism-among-patients-treated-with-rivaroxaban-compared-to-enoxaparin
#14
Megan D Nicklaus, Shannon L Ludwig, Jacob K Kettle
Purpose Although low-molecular-weight heparin (LMWH) remains the standard of care, factor Xa inhibitors such as rivaroxaban may serve as an alternative treatment for venous thromboembolism (VTE) in patients with active malignancy. The purpose of the analysis was to evaluate outcomes of VTE management in cancer patients treated with rivaroxaban compared to enoxaparin. Methods This single-center retrospective analysis was conducted on patients with malignancy-associated VTE initiated on treatment with either rivaroxaban or enoxaparin...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29262430/reversal-of-oral-anticoagulants-for-intracerebral-hemorrhage-patients-best-strategies
#15
Lanting Fuh, Jonathan H Sin, Joshua N Goldstein, Bryan D Hayes
In patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis...
December 2017: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29260434/study-of-binding-interaction-of-rivaroxaban-with-bovine-serum-albumin-using-multi-spectroscopic-and-molecular-docking-approach
#16
Tanveer A Wani, Haitham AlRabiah, Ahmed H Bakheit, Mohd Abul Kalam, Seema Zargar
BACKGROUND: Rivaroxaban is a direct inhibitor of coagulation factor Xa and is used for venous thromboembolic disorders. The rivaroxaban interaction with BSA was studied to understand its PK and PD (pharmacokinetics and pharmacokinetics) properties. Multi-spectroscopic studies were used to study the interaction which included UV spectrophotometric, spectrofluorometric and three dimensional spectrofluorometric studies. Further elucidation of data was done by molecular simulation studies to evaluate the interaction behavior between BSA and rivaroxaban...
December 20, 2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/29260237/-anticoagulation-in-geriatric-patients-with-atrial-fibrillation-with-what-and-for-whom-no-more
#17
REVIEW
P Bahrmann, M Christ
Based on established risk scores, such as the CHA2DS2-VASc score, the indications for oral anticoagulation are given for patients over 65 years old with atrial fibrillation and even more so for patients over 75 years old. Before beginning anticoagulation a geriatric assessment for evaluation of the cognitive ability, the activities of daily living and the risk of falling should be made because of the known complications of anticoagulation. Geriatric patients with non-valvular atrial fibrillation (AF) are increasingly being treated with non-vitamin K antagonist oral anticoagulants (NOAC) to prevent ischemic stroke...
December 19, 2017: Herz
https://www.readbyqxmd.com/read/29249166/safety-and-efficacy-of-rivaroxaban-for-the-secondary-prevention-following-acute-coronary-syndromes-among-biomarker-positive-patients-insights-from-the-atlas-acs-2-timi-51-trial
#18
Serge Korjian, Eugene Braunwald, Yazan Daaboul, Freek Verheugt, Christoph Bode, Michal Tendera, Purva Jain, Alexei Plotnikov, Paul Burton, C Michael Gibson
BACKGROUND: Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patients with prior acute coronary syndrome (ACS). Inhibition of thrombin generation among high-risk ACS patients (biomarker-positive ACS) with the factor Xa inhibitor rivaroxaban may limit ongoing thrombus formation and myocardial necrosis and thereby improve clinical outcomes. OBJECTIVES AND METHODS: ATLAS ACS 2-TIMI 51 was a double-blind, placebo-controlled clinical trial that randomized ACS patients to either rivaroxaban 2...
December 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/29242919/association-of-novel-oral-antithrombotics-with-the-risk-of-intraocular-bleeding
#19
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
#20
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
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