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https://www.readbyqxmd.com/read/29784539/revisiting-antithrombin-in-health-and-disease-congenital-deficiencies-and-genetic-variants-and-laboratory-studies-on-%C3%AE-and-%C3%AE-forms
#1
REVIEW
Jean Amiral, Jerard Seghatchian
Antithrombin [AT] is the main inhibitor for activated plasma coagulation serine esterases, inhibiting thrombin, Factors Xa and IXa, but also Factors XIIa, XIa, VIIa, kallicrein, and plasmin. Its activity is highly enhanced by heparin, through binding to the pentasaccharide sequences, for inhibition of all coagulation proteases, except thrombin, which inhibition requires its additional binding to the heparin polysaccharide chain. However, AT is the major inhibitor of thrombin in the blood circulation. Congenital or acquired deficiencies of AT expose affected patients to an increased risk of developing unprovoked and recurrent thrombo-embolic diseases...
April 19, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29780621/thromboembolism-prophylaxis-in-orthopaedics-an-update
#2
Dimitrios A Flevas, Panayiotis D Megaloikonomos, Leonidas Dimopoulos, Evanthia Mitsiokapa, Panayiotis Koulouvaris, Andreas F Mavrogenis
Venous thromboembolism (VTE) is a serious complication during and after hospitalization, yet is a preventable cause of in-hospital death.Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients is in the range of 10% to 40%, while it ranges up to 40% to 60% in major orthopaedic surgery. With routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months are in the range of 1.3% to 10%.VTE prophylaxis methods are divided into mechanical and pharmacological...
April 2018: EFORT Open Reviews
https://www.readbyqxmd.com/read/29777813/polyphenolic-polysaccharide-conjugates-from-flowers-and-fruits-of-single-seeded-hawthorn-crataegus-monogyna-jacq-chemical-profiles-and-mechanisms-of-anticoagulant-activity
#3
Izabela Pawlaczyk-Graja
The polyphenolic-polysaccharide conjugates were isolated from flowers and fruits of medicinal plant Crataegus monogyna Jacq. (Lindm.) by the alkaline extraction, followed by neutralization, partitioning with organic solvents and dialysis against water. The isolates from flowers as well as from fruits were homogenous macromolecular compounds, with a molecular weight over 760 × 103  g/mol and 970 × 103  g/mol, respectively, what was assessed in HPGPC analysis. Both products were characterized spectrophotometrically, and by GLC-MS, FT-IR and NMR techniques...
May 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775297/factor-xia-inhibitors-as-new-anticoagulants
#4
Mimi L Quan, Donald J P Pinto, Joanne M Smallheer, William R Ewing, Karen A Rossi, Joseph M Luettgen, Dietmar A Seiffert, Ruth R Wexler
With the introduction of thrombin and factor Xa inhibitors to the oral anticoagulant market, significant improvements in both efficacy and safety have been achieved. Early clinical and preclinical data suggest that inhibitors of factor XIa can provide a still safer alternative, with expanded efficacy for arterial indications. This Perspective provides an overview of target rationale and details of the discovery and development of inhibitors of factor XIa as next generation antithrombotic agents.
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29769259/novel-therapeutics-for-hemophilia-and-other-bleeding-disorders
#5
Michael U Callaghan, Robert Sidonio, Steven W Pipe
Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment for these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase III trial in people with hemophilia A and inhibitors...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29766772/rivaroxaban-for-stroke-prevention-after-embolic-stroke-of-undetermined-source
#6
Robert G Hart, Mukul Sharma, Hardi Mundl, Scott E Kasner, Shrikant I Bangdiwala, Scott D Berkowitz, Balakumar Swaminathan, Pablo Lavados, Yongjun Wang, Yilong Wang, Antonio Davalos, Nikolay Shamalov, Robert Mikulik, Luis Cunha, Arne Lindgren, Antonio Arauz, Wilfried Lang, Anna Czlonkowska, Jens Eckstein, Rubens J Gagliardi, Pierre Amarenco, Sebastian F Ameriso, Turgut Tatlisumak, Roland Veltkamp, Graeme J Hankey, Danilo Toni, Daniel Bereczki, Shinichiro Uchiyama, George Ntaios, Byung-Woo Yoon, Raf Brouns, Matthias Endres, Keith W Muir, Natan Bornstein, Serefnur Ozturk, Martin J O'Donnell, Matthys M De Vries Basson, Guillaume Pare, Calin Pater, Bodo Kirsch, Patrick Sheridan, Gary Peters, Jeffrey I Weitz, W Frank Peacock, Ashkan Shoamanesh, Oscar R Benavente, Campbell Joyner, Ellison Themeles, Stuart J Connolly
Background Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. Methods We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source...
May 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29764497/activated-prothrombin-complex-concentrate-to-reverse-the-factor-xa-inhibitor-apixaban-effect-before-emergency-surgery-a-case-series
#7
Nina Haagenrud Schultz, Runar Lundblad, Pål Andre Holme
BACKGROUND: The lack of an antidote against factor Xa inhibitors in case of major bleeding or need for urgent surgery is a concern to clinicians. Guidelines on managing major bleeding in patients under anticoagulation with a factor Xa inhibitor suggest several hemostatic agents to reverse the effect, but there is no consensus regarding the choice of drug or appropriate dose. The ability of prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa to reverse the effect of factor Xa inhibitors has been evaluated in animal studies, in vitro studies, and healthy volunteers, but not yet in randomized clinical studies...
May 16, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29761540/apixaban-decreases-brain-thrombin-activity-in-a-male-mouse-model-of-acute-ischemic-stroke
#8
Doron Bushi, Joab Chapman, Anton Wohl, Efrat Shavit Stein, Ekaterina Feingold, David Tanne
Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I...
May 14, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29760204/model-based-meta-analysis-to-evaluate-optimal-doses-of-direct-oral-factor-xa-inhibitors-in-atrial-fibrillation-patients
#9
Hideki Yoshioka, Hiromi Sato, Hiroto Hatakeyama, Akihiro Hisaka
The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29758017/the-effects-of-dabigatran-and-rivaroxaban-on-markers-of-polymorphonuclear-leukocyte-activation
#10
Guy A Richards, Annette Theron, Gregory Tintinger, Ronald Anderson
Dabigatran is an oral direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor. Dabigatran has been implicated in the etiology of acute coronary syndromes and as these occur following inflammatory changes in the endothelium, we investigated the inflammatory potential of these agents in vitro. In order to do so, polymorphonuclear leukocytes (PMNL) were isolated from heparinized venous blood from non-smoking, healthy adults and exposed to dabigatran or rivaroxaban (0.5⁻10 µM). Generation of reactive oxygen species (ROS), elastase release, cytosolic Ca2+ fluxes, neutrophil extracellular trap (NET) formation and cell viability were measured using chemiluminescence, spectrophotometric and flow cytometric procedures respectively...
May 14, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29754512/-stroke-prevention-in-the-elderly-effectiveness-and-safety-of-edoxaban-in-elderly-patients-according-to-the-results-of-the-engage-af-study
#11
László Márk
Atrial fibrillation is the most common clinically relevant arrhythmia frequently causing systemic thromboembolic events. Traditionally vitamin K antagonists had been used for decades to prevent these events. The emerging of the new direct anticoagulants has revolutionized this treatment and a gradual growth and extensive spread of usage is expected. The latest one approved in Hungary, edoxaban, is a factor Xa inhibitor. Once-daily administration and favourable safety profile are major benefits of this drug...
May 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29748353/gastrointestinal-bleeding-with-edoxaban-versus-warfarin-results-from-the-engage-af-timi-48-trial-effective-anticoagulation-with-factor-xa-next-generation-in-atrial-fibrillation-thrombolysis-in-myocardial-infarction
#12
James Aisenberg, Prapti Chatterjee-Murphy, Kathryn Friedman Flack, Jeffrey I Weitz, Christian T Ruff, Francesco Nordio, Michele F Mercuri, Youngsook Choi, Elliott M Antman, Eugene Braunwald, Robert P Giugliano
BACKGROUND: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction) compared higher-dose edoxaban regimen (HD-ER) and lower-dose edoxaban regimen with well-managed warfarin in 21 105 patients with atrial fibrillation. The risk factors and clinical impact of gastrointestinal bleeding (GIB) in this trial have not been described in detail. METHODS AND RESULTS: This analysis was undertaken to identify risk factors for major GIB (MGIB) and compare the severity and outcomes of GIB with edoxaban and warfarin...
May 2018: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/29746227/comparison-of-an-oral-factor-xa-inhibitor-with-low-molecular-weight-heparin-in-patients-with-cancer-with-venous-thromboembolism-results-of-a-randomized-trial-select-d
#13
Annie M Young, Andrea Marshall, Jenny Thirlwall, Oliver Chapman, Anand Lokare, Catherine Hill, Danielle Hale, Janet A Dunn, Gary H Lyman, Charles Hutchinson, Peter MacCallum, Ajay Kakkar, F D Richard Hobbs, Stavros Petrou, Jeremy Dale, Christopher J Poole, Anthony Maraveyas, Mark Levine
Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited...
May 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29741099/economic-evaluation-of-prescribing-conventional-and-newer-oral-anticoagulants-in-older-adults
#14
Syed Shahzad Hasan, Chia Siang Kow, Louise E Curley, Darrin L Baines, Zaheer-Ud-Din Babar
Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted...
May 9, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29739329/thrombin-and-factor-xa-link-the-coagulation-system-with-liver-fibrosis
#15
Ameet Dhar, Fouzia Sadiq, Quentin M Anstee, Adam P Levene, Robert D Goldin, Mark R Thursz
BACKGROUND: Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. METHODS: HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated...
May 8, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29727017/recent-advances-in-the-discovery-and-development-of-factor-xi-xia-inhibitors
#16
REVIEW
Rami A Al-Horani, Daniel K Afosah
Factor XIa (FXIa) is a serine protease homodimer that belongs to the intrinsic coagulation pathway. FXIa primarily catalyzes factor IX activation to factor IXa, which subsequently activates factor X to factor Xa in the common coagulation pathway. Growing evidence suggests that FXIa plays an important role in thrombosis with a relatively limited contribution to hemostasis. Therefore, inhibitors targeting factor XI (FXI)/FXIa system have emerged as a paradigm-shifting strategy so as to develop a new generation of anticoagulants to effectively prevent and/or treat thromboembolic diseases without the life-threatening risk of internal bleeding...
May 4, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29723040/role-of-the-blood-coagulation-cascade-in-hepatic-fibrosis
#17
Asmita Pant, Anna K Kopec, James P Luyendyk
Liver is the primary source of numerous proteins critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis...
May 3, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29720261/efficacy-and-safety-of-adding-rivaroxaban-to-the-anti-platelet-regimen-in-patients-with-coronary-artery-disease-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#18
Jun Yuan
BACKGROUND: Rivaroxaban, a direct factor Xa inhibitor, has seldom been used in patients with coronary artery disease. In this analysis, we aimed to systematically compare the efficacy and safety of rivaroxaban in addition to the anti-platelet regimen in patients with coronary artery disease. METHODS: Online databases (MEDLINE, EMBASE, Cochrane database, www.ClinicalTrials.gov and Google scholar were searched for randomized controlled trials which were exclusively based on patients with coronary artery disease; and which compared efficacy (cardiovascular outcomes) and safety (bleeding outcomes) outcomes with the addition of rivaroxaban to the other anti-platelet agents...
May 2, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29709396/rivaroxaban-plus-percutaneous-catheter-directed-treatment-for-a-patient-with-massive-pulmonary-embolism-and-colporrhagia
#19
Wuchao Wang
Massive pulmonary embolism (PE) is defined by acute PE with sustained systemic arterial hypotension that is below 90 mm Hg for at least 15 min or requires inotropic agents (Jaff et al., 2011). For patients with absolute contraindications to thrombolysis, interventional treatment requires the removal of obstructing thrombi from the main pulmonary arteries to facilitate RV recovery and improve symptoms and survival (European Respiratory Society et al., 2014). For patients with acute PE, anticoagulation is recommended, with the objective of preventing both early death and recurrent symptomatic or fatal VTE...
April 19, 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29709361/partial-thromboplastin-time-is-more-predictive-of-bleeding-than-anti-xa-levels-in-heparinized-pediatric-patients-after-cardiac-surgery
#20
Olubunmi O Oladunjoye, Lynn A Sleeper, Asha G Nair, Cameron C Trenor, Christina VanderPluym, John N Kheir, Sitaram M Emani
OBJECTIVES: Anticoagulation with unfractionated heparin (UFH) after pediatric cardiac surgery can be monitored using either activated partial thromboplastin time (aPTT) or anti-factor Xa activity (anti-Xa). However, correlation of bleeding with either of these laboratory values has not been established. We sought to determine the correlation between bleeding events and aPTT and anti-Xa in patients who undergo anticoagulation after congenital heart surgery. METHODS: We prospectively studied pediatric patients treated with UFH after cardiac surgery over an 11-month period...
April 4, 2018: Journal of Thoracic and Cardiovascular Surgery
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