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Novel anticoagulants

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https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#1
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096572/current-and-emerging-treatments-for-hypercholesterolemia-a-focus-on-statins-and-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-for-perioperative-clinicians
#2
REVIEW
Terrence L Trentman, Steven G Avey, Harish Ramakrishna
Statins are a mainstay of hyperlipidemia treatment. These drugs inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and have beneficial effects on atherosclerosis including plaque stabilization, reduction of platelet activation, and reduction of plaque proliferation and inflammation. Statins also have a benefit beyond atherosclerotic plaque, including anticoagulation, vasodilatation, antioxidant effects, and reduction of mediators of inflammation. In the perioperative period, statins appear to contribute to improved outcomes via these mechanisms...
October 2016: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28091958/identification-and-anticoagulant-activity-of-a-novel-kunitz-type-protein-ha11-from-the-salivary-gland-of-the-tick-hyalomma-asiaticum
#3
Houshuang Zhang, Ruiqiong Qiao, Haiyan Gong, Jie Cao, Yongzhi Zhou, Jinlin Zhou
Kunitz/bovine pancreatic trypsin inhibitor proteins are abundant in the salivary glands of ticks and perform multiple functions in blood feeding, including inhibiting blood coagulation, regulating host blood supply and disrupting host angiogenesis. In this study, we identified a novel gene designated HA11 (Hyalomma asiaticum 11 kDa protein) from the salivary gland of the tick H. asiaticum. HA11 is encoded by a gene with an open reading frame of 306 bp that is translated into a deduced 101 amino acid 11 kDa protein that shares 27% sequence identity with a Kunitz-like protease inhibitor precursor in Amblyomma variegatum...
January 13, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28089863/prevention-of-thrombosis-in-hypercoagulable-patients-undergoing-microsurgery-a-novel-anticoagulation-protocol
#4
Jonas A Nelson, Cyndi U Chung, Andrew R Bauder, Liza C Wu
BACKGROUND: Hypercoagulable conditions are often considered relative contraindications to free flap reconstruction. This paper presents and critically examines a novel anticoagulation regimen developed to address this disease state. METHODS: Hypercoagulable patients who underwent free tissue transfer between 2007 and 2015 were identified. From 2011, all such patients were subjected to a novel anticoagulation protocol involving an intravenous bolus of 2000 U of unfractionated heparin prior to microvascular pedicle anastomosis, followed by a heparin infusion at 500 U/h, which was postoperatively increased to therapeutic levels...
December 18, 2016: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
https://www.readbyqxmd.com/read/28088608/gene-analysis-of-six-cases-of-congenital-protein-s-deficiency-and-functional-analysis-of-protein-s-mutations-a139v-c449f-r451q-c475f-a525v-and-d599tfster13
#5
Fumina Taniguchi, Eriko Morishita, Akiko Sekiya, Haruka Nomoto, Shiori Katsu, Shounosuke Kaneko, Hidesaku Asakura, Shigeki Ohtake
Congenital deficiency of protein S (PS), an anticoagulant factor, leads to venous thrombosis, with onset predominantly beginning in adolescence. In the present study, gene analysis of six unrelated Japanese families diagnosed with congenital PS deficiency identified five missense mutations in the PROS1 gene - c.757C>T (Ala139Val; A139V), c.1346 G>T (Cys449Phe; C449F), c.1352G>A (Arg451Gln; R451Q), c.1424G>T (Cys475Phe; C475F) and c.1574C>T (Ala525Val; A525V) - and one frameshift mutation, c.2135delA (Asp599ThrfsTer13; D599TfsTer13)...
December 24, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28087311/-the-role-of-novel-oral-anticoagulants-in-patients-undergoing-cryoballoon-ablation-for-atrial-fibrillation
#6
Giannis Baltogiannis, Gian-Battista Chierchia, Giulio Conte, Juan Sieira, Giacomo Di Giovanni, Giuseppe Ciconte, Carlo de Asmundis, Yukio Saitoh, Kristel Wauters, Ghazala Irfan, Pedro Brugada
AIM: Peri-procedural thromboembolic (TE) and hemorrhagic events are complications of major concern for patients undergoing cryoballoon (CB) ablation for atrial fibrillation (AF). While peri-procedural anticoagulation management could decrease the incidence of these complications, data on CB ablation are scarce. The role of novel oral anticoagulants (NOACs) has not been thoroughly tested in this population. METHODS: In the present study, we sought to assess acute peri-procedural complications in patients undergoing CB ablation for AF under different anticoagulation regimens; anticoagulation administration was performed according to the CHA2DS2-VASc score guidelines...
November 16, 2016: Hellenic Journal of Cardiology: HJC, Hellēnikē Kardiologikē Epitheōrēsē
https://www.readbyqxmd.com/read/28071818/safety-profile-of-the-direct-oral-anticoagulants-an-analysis-of-the-who-database-of-adverse-drug-reactions
#7
Luca Monaco, Chiara Biagi, Valentino Conti, Mauro Melis, Monia Donati, Mauro Venegoni, Alberto Vaccheri, Domenico Motola
AIM: Direct oral anticoagulants (DOACs) have shown non-inferiority to warfarin for stroke prevention in non-valvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase...
January 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28068607/micro-electromechanical-film-bulk-acoustic-sensor-for-plasma-and-whole-blood-coagulation-monitoring
#8
Da Chen, Shuren Song, Jilong Ma, Zhen Zhang, Peng Wang, Weihui Liu, Qiuquan Guo
Monitoring blood coagulation is an important issue in the surgeries and the treatment of cardiovascular diseases. In this work, we reported a novel strategy for the blood coagulation monitoring based on a micro-electromechanical film bulk acoustic resonator. The resonator was excited by a lateral electric field and operated under the shear mode with a frequency of 1.9GHz. According to the apparent step-ladder curves of the frequency response to the change of blood viscoelasticity, the coagulation time (prothrombin time) and the coagulation kinetics were measured with the sample consumption of only 1μl...
December 30, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28064150/a-novel-risk-prediction-score-in-atrial-fibrillation-for-a-net-clinical-outcome-from-the-engage-af-timi-48-randomized-clinical-trial
#9
Christina L Fanola, Robert P Giugliano, Christian T Ruff, Marco Trevisan, Francesco Nordio, Michele F Mercuri, Elliott M Antman, Eugene Braunwald
AIMS: The choice between initiating a non-vitamin K antagonist oral anticoagulant (NOAC) and a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) may be challenging. To assist in this decision, we developed a risk score to identify patients for whom a therapeutic benefit of NOACs over VKA is predicted. METHODS AND RESULTS: ENGAGE AF-TIMI 48 was a randomized clinical trial of edoxaban vs. warfarin in 21 105 patients with AF. Cox proportional hazard models identified factors associated with a serious net clinical outcome (NCO) of disabling stroke, life-threatening bleeding, and all-cause mortality in VKA naïve patients from the warfarin arm...
January 6, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28061983/the-use-of-novel-oral-anticoagulants-in-cancer-patients-with-venous-thromboembolism
#10
REVIEW
Stamatis J Karakatsanis, Aikaterini Roumpi, Konstantinos N Syrigos
Venous thromboembolism (VTE) is not uncommon among patients with cancer and is one of the major causes of mortality and morbidity. Treatment with low-molecular-weight heparin (LMWH) is effective, yet accompanied by the need for daily administration of injections for a prolonged time and (even rarely) thrombocytopenia. The discovery of novel oral anticoagulants (NOACs) was based on an effort to improve the pharmacodynamic and pharmacokinetic properties of previous generation anticoagulants while maintaining efficacy without the need for daily subcutaneous administration and frequent laboratory monitoring...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#11
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28056758/thrombotic-management-of-antiphospholipid-syndrome-towards-novel-targeted-therapies
#12
Md Asiful Islam, Fahmida Alam, Kah Keng Wong, Mohammad Amjad Kamal, Siew Hua Gan
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology...
5, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28049606/an-insight-into-the-sialome-of-hyalomma-excavatum
#13
José M C Ribeiro, Mirko Slovák, Ivo M B Francischetti
Tick saliva contains hundreds or thousands of proteins that help blood feeding by impairing their hosts' hemostasis, inflammation and immunity. Salivary gland transcriptomes allow the disclosure of this pharmacologically active potion that consists of several multi-gene families, many of which are tick-specific. We here report the "de novo" assembly of ∼138 million reads deriving from a cDNA library from salivary glands of adult male and female Hyalomma excavatum leading to the public deposition of 5337 coding sequences to GenBank...
December 21, 2016: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/28042092/increased-risk-of-major-bleeding-in-underweight-patients-with-atrial-fibrillation-who-were-prescribed-novel-oral-anticoagulants
#14
Chan Soon Park, Eue-Keun Choi, Hyue Mee Kim, So-Ryoung Lee, Myung-Jin Cha, Seil Oh
BACKGROUND: There is a paucity of evidence regarding the effects of new oral anticoagulants (NOACs) in underweight patients with atrial fibrillation (AF). OBJECTIVE: We sought to evaluate the efficacy and safety of NOACs in underweight AF patients. METHODS: We analyzed 1353 AF patients who were prescribed NOACs according to their body mass index (BMI): underweight (UW, n = 62, BMI < 18.5 kg/m(2)), normal weight (NW, n=753, BMI 18.5-24.9 kg/m(2)), and overweight-to-obese (OW, n = 538, BMI ≥ 25...
December 29, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28040750/a-minimally-invasive-approach-for-open-surgical-thoracoabdominal-aortic-replacement-experimental-concept-for-a-novel-surgical-procedure
#15
Terézia B Andrási, Violetta Kékesi, Béla Merkely, Marius Grossmann, Bernhard C Danner, Friedrich A Schöndube
OBJECTIVES: We aimed to develop a simple, reliable, and timesaving technique for the therapy of thoracoabdominal aortic (TAA) aneurysms that are not suitable for endovascular repair. METHODS: In this pilot study, we sought to combine the advantages of classic open vascular procedure with the use of endoscopic surgical tools and small skin incisions to develop a minimally invasive approach for TAA replacement. The following procedures were used: endoscopic exposure and closure of the lower intercostal arteries; small posterolateral thoracotomy and left retroperitoneal incisions to expose the anastomotic regions of the aorta; partial anticoagulation; passive bypass and sequential aortic clamping; tunnelling of the graft through the native aortic lumen (endoaneurysmorrhaphy) and open performance of vascular anastomosis...
December 31, 2016: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28038749/structure-and-anticoagulant-property-of-a-sulfated-polysaccharide-isolated-from-the-green-seaweed-monostroma-angicava
#16
Na Li, Xue Liu, Xiaoxi He, Shuyao Wang, Sujian Cao, Zheng Xia, Huali Xian, Ling Qin, Wenjun Mao
An anticoagulant-active polysaccharide PF2 was extracted with boiling water from the green seaweed Monostroma angicava, further purified by anion-exchange and size-exclusion chromatography. PF2 was a rhamnan-type sulfated polysaccharide with molecular weight of about 88.1kDa. Results of chemical and spectroscopic analyses demonstrated that PF2 consisted of→3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→residues, with partially branches at C-2 of→3)-α-l-Rhap-(1→residues. Sulfate groups were substituted at C-3 of →2)-α-l-Rhap-(1→ residues...
March 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28032893/anticoagulation-endpoints-with-clinical-implementation-of-warfarin-pharmacogenetic-dosing-in-a-real-world-setting-a-proposal-for-a-new-pharmacogenetic-dosing-approach
#17
M J Arwood, J Deng, K Drozda, O Pugach, E A Nutescu, S Schmidt, J D Duarte, L H Cavallari
Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7...
November 5, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28029411/atrial-fibrillation-and-heart-failure-factors-influencing-the-choice-of-oral-anticoagulant
#18
REVIEW
Louise A E Brown, Christopher J Boos
Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors...
September 30, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28007598/identification-of-acap5-as-a-novel-factor-xa-inhibitor-with-both-direct-and-allosteric-inhibition
#19
Yuanjun Zhu, Yuan Lin, Xiaoyan Liu, Wenhui Hu, Yinye Wang
Ancylostoma caninum anticoagulant peptide 5 (AcAP5) is a potent inhibitor for coagulation factor Xa (FXa). Previous studies show that AcAP5 binds to FXa at the active site, and/or the exosite. The active site-binding contributes to direct blocking of FXa catalytic activity, but the effect of exosite-binding and the underlying mechanism remain unknown. To investigate whether and how the exosite-binding affects FXa function, we prepared several AcAP5 mutants with modifications to the active site-binding or exosite-binding region...
December 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28007362/best-clinical-practice-controversies-in-outpatient-management-of-acute-pulmonary-embolism
#20
Brit Long, Alex Koyfman
BACKGROUND: Pulmonary embolism (PE) is a common condition managed in the emergency department (ED), with a wide range of morbidity and mortality. Patients are classically admitted for treatment and monitoring of anticoagulation. OBJECTIVE: We sought to evaluate the controversy concerning outpatient therapy for patients with acute PE and investigate the feasibility, safety, and efficacy of outpatient management. DISCUSSION: Patients with venous thromboembolism have historically been admitted for treatment and monitoring for concern of worsening disease or side effects of anticoagulation (bleeding)...
December 19, 2016: Journal of Emergency Medicine
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