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https://www.readbyqxmd.com/read/28943551/cholesterol-crystal-embolism-induced-by-direct-factor-xa-inhibitor-a-first-case-report
#1
Hideaki Oka, Taro Kamimura, Yuki Hiramatsu, Kento Fukumitsu, Rei Iwata, Mika Kondo, Yutaro Hirashima, Seishi Aihara, Atsumi Harada, Kazuhiko Tsuruya
An 80-year-old man presented at our hospital with renal failure. He had been treated with edoxaban, an oral direct factor Xa inhibitor, for deep vein thrombosis for 10 months prior to admission. Although the pulses in his bilateral pedal arteries were palpable, cyanosis was present in the bilateral toes. Laboratory data indicated azotemia and eosinophilia. A skin biopsy confirmed a diagnosis of cholesterol crystal embolism (CCE). Because no invasive vascular procedure was performed, we assumed that CCE was related to edoxaban...
September 25, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28942999/optimized-purification-of-a-fusion-protein-by-reversed-phase-high-performance-liquid-chromatography-informed-by-the-linear-solvent-strength-model
#2
Isaac B Falconer, Colin T Mant, C James McKnight, Liliya Vugmeyster, Robert Hodges
Fusion protein systems are commonly used for expression of small proteins and peptides. An important criterion for a fusion protein system to be useful is the ability to separate the protein of interest from the tag. Additionally, because no protease cleaves fusion proteins with 100% efficiency, the ability to separate the desired peptide from any remaining uncleaved protein is also necessary. This is likely to be the more difficult task as at least a portion of the sequence of the fusion protein is identical to that of the protein of interest...
September 13, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28937618/novel-fxa-inhibitor-identification-through-integration-of-ligand-and-structure-based-approaches
#3
Carlos F Lagos, Gerardine F Segovia, Nicolás Nuñez-Navarro, Mario A Faúndez, Flavia C Zacconi
Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and electrostatic similarity search and protein-ligand docking to discover novel FXa-targeted scaffolds for further development of inhibitors. From an initial set of 260,000 compounds from the NCI Open database, 30 potential FXa inhibitors were identified and selected for in vitro biological evaluation...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937536/enoxaparin-population-pharmacokinetics-in-the-first-year-of-life
#4
Brady S Moffett, Marianne Galati, Donald Mahoney, YoungNa Lee-Kim, Jun Teruya, Mona D Shah, Donald L Yee
Aims Enoxaparin dosing requirements in the first year of life can be highly variable. Characterization of pharmacokinetics in this patient population can assist in dosing. METHODS: Patients less than one year post-natal age who received enoxaparin and had an anti-factor Xa activity level drawn as inpatients were identified through the pharmacy database over a five-year period. Patients on renal replacement therapy or with hyperbilirubinemia were excluded. Data collection included demographic variables, indication for enoxaparin, enoxaparin doses, anti-factor Xa activity levels, serum creatinine, hemoglobin, hematocrit, platelet count, and urine output over the previous 24 hours...
September 19, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28935233/substrate-delivery-mechanism-and-the-role-of-membrane-curvature-in-factor-x-activation-by-extrinsic-tenase
#5
Tatiana A Kovalenko, Mikhail A Panteleev, Anastasia N Sveshnikova
Membrane-bound enzyme complex of extrinsic tenase (VIIa/TF) is believed to be the primary activator of blood clotting in vivo. This complex (where factor VIIa (FVIIa) is a catalytically active part and tissue factor (TF) is its essential cofactor) activates its primary substrate factor X (FX) leading to factor Xa (FXa) ('a' stands for 'activated'). Both FX and FXa are able to bind to phospholipid membrane and, therefore, are distributed between solution and membrane surface. As a result, two possible mechanisms of substrate delivery to the extrinsic tenase exist: via lateral diffusion on the membrane surface or directly from the solution...
September 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28935034/persistence-with-dabigatran-therapy-at-2%C3%A2-years-in-patients-with-atrial-fibrillation
#6
Miney Paquette, Lionel Riou França, Christine Teutsch, Hans-Christoph Diener, Shihai Lu, Sergio J Dubner, Chang Sheng Ma, Kenneth J Rothman, Kristina Zint, Jonathan L Halperin, Menno V Huisman, Gregory Y H Lip, Robby Nieuwlaat
BACKGROUND: Guidelines recommend long-term oral anticoagulation therapy for stroke prevention in patients with atrial fibrillation (AF). Treatment discontinuation rates in vitamin K antagonist (VKA)-treated patients are high but may be lower with non-VKA oral anticoagulant agents. OBJECTIVES: The goal of this study was to describe and explore predictors of dabigatran etexilate persistence in patients with newly diagnosed AF over 2 years of follow-up. METHODS: Consecutive patients newly diagnosed with AF and ≥1 stroke risk factor were followed up for 2 years...
September 26, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28933799/rivaroxaban-for-preventing-venous-thromboembolism-in-high-risk-ambulatory-patients-with-cancer-rationale-and-design-of-the-cassini-trial-rationale-and-design-of-the-cassini-trial
#7
Alok Khorana, Saroj Vadhan-Raj, Nicole M Kuderer, Ted Wun, Howard Liebman, Gerald Soff, Chandra Belani, Eileen M O'Reilly, Robert McBane, John Eikelboom, C V Damaraju, Karen Beyers, Flavia Dietrich, Ajay Kakkar, Hanno Riess, Renata D'Alpino Peixoto, Gary H Lyman
Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2)...
September 21, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28930804/venous-thromboembolism-in-gynecological-malignancy
#8
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...
September 19, 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
#9
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...
September 19, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28918992/anti-factor-xa-levels-in-patients-undergoing-laparoscopic-sleeve-gastrectomy-2-different-dosing-regimens-of-enoxaparin
#10
Shaul Gelikas, Shai Meron Eldar, Guy Lahat
BACKGROUND: Morbidly obese patients undergoing bariatric surgery are at risk for developing venous thromboembolic events. Data regarding the appropriate dosing strategy in this special population is limited. OBJECTIVE: To evaluate 2 different dosing regimens of enoxaparin in a prospective cohort of patients undergoing laparoscopic sleeve gastrectomy. SETTING: University hospital, Israel METHODS: The study cohort consisted of 54 patients divided into 2 groups...
July 27, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28904343/engineered-factor-xa-variants-retain-procoagulant-activity-independent-of-direct-factor-xa-inhibitors
#11
Daniël Verhoef, Koen M Visscher, C Ruben Vosmeer, Ka Lei Cheung, Pieter H Reitsma, Daan P Geerke, Mettine H A Bos
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28902081/activated-partial-thromboplastin-time-versus-anti-factor-xa-levels-for-monitoring-unfractionated-heparin-therapy-in-children-an-institutional-experience
#12
Gary M Woods, Joseph Stanek, Sheilah Harrison, Karen Texter, Bryce A Kerlin, Amy L Dunn, Riten Kumar
No abstract text is available yet for this article.
September 8, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28901221/direct-oral-anticoagulant-reversal-how-when-and-issues-faced
#13
Mikhail S Dzeshka, Daniele Pastori, Gregory Y H Lip
The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. Areas covered: In the current review, risk of major bleeding in patients taking NOACs and general approaches to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed...
September 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28888219/factor-xa-inhibition-by-rivaroxaban-in-the-trough-steady-state-can-significantly-reduce-thrombin-generation
#14
Shigeo Horinaka, Rie Sugawara, Yutaka Yonezawa, Toshihiko Ishimitsu
AIMS: The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. METHODS: A single-centre, prospective, non-randomised, drug intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with non-valvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and anti-factor Xa chromogenic assay...
September 9, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28886856/outcome-of-patients-receiving-thrombolytic-therapy-while-on-rivaroxaban-for-nonvalvular-atrial-fibrillation-from-rivaroxaban-once-daily-oral-direct-factor-xa-inhibition-compared-with-vitamin-k-antagonism-for-prevention-of-stroke-and-embolism-trial-in-atrial
#15
Sean T Chen, Anne S Hellkamp, Richard C Becker, Scott D Berkowitz, Günter Breithardt, Keith A A Fox, Werner Hacke, Jonathan L Halperin, Graeme J Hankey, Kenneth W Mahaffey, Christopher C Nessel, Jonathan P Piccini, Daniel E Singer, Manesh R Patel
The safety of intravenous thrombolysis in patients taking rivaroxaban has not been well established. We retrospectively analyzed the outcomes of all patients who received thrombolytic therapy in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). A review of medical and adverse event records for patients receiving thrombolytic therapy while enrolled in ROCKET AF was performed to determine their baseline characteristics, indications for thrombolysis, and type of agent used...
August 7, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28884611/an-evaluation-of-the-activated-partial-thromboplastin-time-waveform
#16
Takeshi Matsumoto, Hideo Wada, Naoki Fujimoto, Junki Toyoda, Yasunori Abe, Kohshi Ohishi, Yoshiki Yamashita, Makoto Ikejiri, Kei Hasegawa, Kei Suzuki, Hiroshi Imai, Kaname Nakatani, Naoyuki Katayama
The activated partial thromboplastin time (APTT) waveform includes several parameters that are related to various underlying diseases. The APTT waveform was examined in various diseases. Regarding the pattern of APTT waveform, a biphasic pattern of the first or second derivative curve (DC) was observed in patients with hemophilia and patients positive for antiphospholipid (aPL) antibodies or coagulation factor VIII (FVIII) inhibitors. The time of the first and second DC and fibrin formation at 1/2 height were prolonged in patients with hemophilia, patients with inhibitors, patients positive for aPL, patients treated with anti-Xa agents, and patients with disseminated intravascular coagulation (DIC)...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28883515/factor-xa-mediates-calcium-flux-in-endothelial-cells-and-is-potentiated-by-igg-from-patients-with-lupus-and-or-antiphospholipid-syndrome
#17
Bahar Artim-Esen, Natalia Smoktunowicz, Thomas McDonnell, Vera M Ripoll, Charis Pericleous, Ian Mackie, Eifion Robinson, David Isenberg, Anisur Rahman, Yiannis Ioannou, Rachel C Chambers, Ian Giles
Factor (F) Xa reactive IgG isolated from patients with antiphospholipid syndrome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic lupus erythematosus (SLE) non APS IgG. FXa signalling via activation of protease-activated receptors (PAR) leads to increased intracellular calcium (Ca(2+)). Therefore, we measured alterations in Ca(2+) levels in human umbilical vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alter these responses...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878512/comparison-of-postoperative-complications-after-total-hip-arthroplasty-among-patients-receiving-aspirin-enoxaparin-warfarin-and-factor-xa-inhibitors
#18
Perez Agaba, Beau J Kildow, Herman Dhotar, Thorsten M Seyler, Michael Bolognesi
Optimal prophylaxis for prevention of venous thromboembolism (VTE) after total joint arthroplasty (TJA) remains debated. The purpose of this study was to compare postoperative complications in patients receiving different VTE chemoprophylactic regimens. Using a nationwide healthcare database, 72,670 THA patients without a history of VTE were identified. Study cohorts received VTE prophylaxis within 30 days postoperatively. Odds ratios and 95% confidence intervals were used to assess 30-day and 90-day postoperative complications (hematoma, hemorrhage, transfusion, pulmonary embolism (PE), VTE, prosthetic joint infection (PJI), and incision/drainage (I&D))...
December 2017: Journal of Orthopaedics
https://www.readbyqxmd.com/read/28877563/intravenous-thrombolysis-in-patients-with-stroke-taking-rivaroxaban-using-drug-specific-plasma-levels-experience-with-a-standard-operation-procedure-in-clinical-practice
#19
David J Seiffge, Christopher Traenka, Alexandros A Polymeris, Sebastian Thilemann, Benjamin Wagner, Lisa Hert, Mandy D Müller, Henrik Gensicke, Nils Peters, Christian H Nickel, Christoph Stippich, Raoul Sutter, Stephan Marsch, Urs Fisch, Raphael Guzman, Gian Marco De Marchis, Philippe A Lyrer, Leo H Bonati, Dimitrios A Tsakiris, Stefan T Engelter
Background and Purpose: Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT). Methods: This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016)...
September 6, 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28875044/decreased-rivaroxaban-levels-in-a-patient-with-cerebral-vein-thrombosis-receiving-phenytoin
#20
Ana F Becerra, Tomas Amuchastegui, Aldo H Tabares
Combined use of antiepileptic drugs and anticoagulants is common. We describe the first case documenting laboratory interaction between rivaroxaban and phenytoin. A 48-year-old woman was admitted to our hospital due to cerebral venous thrombosis, bilateral pulmonary embolism, and deep vein thrombosis. She came from a small town with difficult access to warfarin monitoring. She was receiving phenytoin 100 mg three times daily (t.i.d.) and started enoxaparin 60 mg twice daily (b.i.d.). An abdominal mass was diagnosed and removed by laparoscopy (gastrointestinal stromal tumor)...
2017: Case Reports in Hematology
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