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Xa inhibitors

Young-A Heo
Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa® ] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors. In May 2018, andexanet alfa received its first global approval in the USA for use in patients treated with rivaroxaban and apixaban, when reversal of anticoagulant effects is required in life-threatening or uncontrolled bleeding...
June 20, 2018: Drugs
Samiullah Khan, Aqsa Gul, Rabia Noreen, Muhammad Ashraf, Sohail Ahmad, Sattar Bakhsh Awan
BACKGROUND: Thrombus is composed of two main substances i.e. red blood cells and aggregated platelets which make a web of inter-connected fibrin proteins. During injury it prevents bleeding, so it is very useful but it can be very dangerous if it is produced in healthy blood vessels and block the blood flow through it. Mural thrombi attaches with the blood vessels but in most cases do not block it completely. Venoms are an incredible source of peptides having amazing bioactivities with varying number of amino acid residues...
June 13, 2018: Protein and Peptide Letters
Craig Basman, Afnan Tariq, Yuvrajsinh J Parmar, Deepak Asti, Neil L Coplan, Varinder P Singh, Carl D Reimers
Pharmacotherapy for percutaneous coronary interventions is essential to optimize the balance between thrombosis and bleeding. Currently, choices abound for the selection of antiplatelet and anticoagulation therapies during percutaneous intervention (PCI). This review article discusses the mechanisms, pharmacokinetics/dynamics, and clinical data behind the various pharmacotherapies including; aspirin, thienopyridines, glycoprotein IIb/IIIa inhibitors, vorapaxar, heparin, direct thrombin inhibitors, and factor Xa inhibitors...
June 19, 2018: Journal of Interventional Cardiology
Magdalena L Bochenek, Tobias Bauer, Rajinikanth Gogiraju, Yona Nadir, Amrit Mann, Tanja Schönfelder, Leonie Hünig, Benjamin Brenner, Thomas Münzel, Philip Wenzel, Stavros Konstantinides, Katrin Schäfer
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in elderly people. Increased expression of tumor suppressor protein 53 (p53) has been implicated in vascular senescence. Here, we examined the importance of endothelial p53 for venous thrombosis and whether endothelial senescence and p53 overexpression are involved in the exponential increase of VTE with age. Mice with conditional, endothelial-specific deletion of p53 (End.p53-KO) and their wild-type littermates (End.p53-WT) underwent subtotal inferior vena cava (IVC) ligation to induce venous thrombosis...
June 12, 2018: Blood Advances
Romain Siriez, Jonathan Evrard, Jean-Michel Dogné, Lionel Pochet, Damien Gheldof, Bernard Chatelain, François Mullier, Jonathan Douxfils
INTRODUCTION:  Betrixaban is a novel direct oral factor Xa inhibitor approved by the Food and Drug Administration for prophylaxis of venous thromboembolism in adult patients hospitalized for an acute illness at risk for thromboembolic complications. Assessment of the anti-coagulant effect of betrixaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced. OBJECTIVE:  The aim of this study is to determine which coagulation assay(s) should be used to assess the impact of betrixaban on haemostasis and provide laboratory guidance for their interpretation...
June 11, 2018: Thrombosis and Haemostasis
G S King, L G Cottingham, R E Hughes, P D Ratliff
WHAT IS KNOWN AND OBJECTIVE: Prothrombin complex concentrate (PCC) is a plasma-derived concentrate used to replenish clotting factors. There are limited recommendations for treating coagulopathy induced by direct oral anticoagulants (DOAC). Data are limited regarding both total dose and repeated dosing with this population. CASE SUMMARY: We describe a case of an adult patient anticoagulated with apixaban who received two 35 unit/kg doses of PCC resulting in suspected pulmonary embolism...
June 9, 2018: Journal of Clinical Pharmacy and Therapeutics
Kate Traynor
No abstract text is available yet for this article.
June 15, 2018: American Journal of Health-system Pharmacy: AJHP
Eiman Ghaffarpasand, Maneli D Tehrani, Jolanta Marszalek, Gerald Chi
Intracardiac thrombus most commonly develops in the left atrial appendage (LAA) and left ventricle (LV) in the setting of atrial fibrillation (AF) and post-myocardial fibrillation (MI), respectively. Current guidelines recommend that patients with post-MI LV or LAA thrombus should be treated with vitamin K antagonist (VKA). However, the use of VKA may be limited by bleeding complications, interactions with various food and drugs, and a narrow therapeutic window requiring frequent monitoring. Thus, non-VKA oral anticoagulants (NOACs) have been attempted as an off-label use for the treatment of intracardiac thrombosis in light of their favorable pharmacologic profile...
June 6, 2018: Journal of Thrombosis and Thrombolysis
Wael Sumaya, William A E Parker, Rebekah Fretwell, Ian R Hall, David S Barmby, James D Richardson, Javaid Iqbal, Zulfiquar Adam, Kenneth P Morgan, Julian P Gunn, Annah E Mason, Heather M Judge, Christopher P Gale, Ramzi A Ajjan, Robert F Storey
Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0...
June 6, 2018: Thrombosis and Haemostasis
Peter van Doorn, Jan Rosing, Connie Duckers, Tilman M Hackeng, Paolo Simioni, Elisabetta Castoldi
BACKGROUND:  Activated factor V (FVa) is a potent procoagulant cofactor in the prothrombinase complex, whereas its precursor factor V (FV) stimulates the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-α (TFPIα), presumably by promoting TFPIα binding to phospholipids. Plasma FV comprises two glycosylation isoforms (FV1 and FV2) with low and high phospholipid-binding affinity, respectively. The FV1/FV2 ratio is increased in carriers of the FV R2 haplotype. OBJECTIVE:  This article demonstrates the TFPIα-cofactor function of FV in plasma and compares FV1 and FV2...
June 4, 2018: Thrombosis and Haemostasis
Ruwan Gunaratne, Shekhar Kumar, James W Frederiksen, Steven Stayrook, Jens L Lohrmann, Kay Perry, Kristin M Bompiani, Charlene V Chabata, Nabil K Thalji, Michelle D Ho, Gowthami Arepally, Rodney M Camire, Sriram Krishnaswamy, Bruce A Sullenger
Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors...
June 4, 2018: Nature Biotechnology
Leonardo Seoane, Marcia Cortés, María Esther Aris Cancela, Juan Furmento, Adrián Baranchuk, Diego Conde
Until recently, vitamin K antagonists were the only drugs available for long-term anticoagulation. The use of these drugs is laborious due to their variable pharmacokinetics and pharmacodynamics. The advent of direct oral anticoagulants has produced a paradigm shift due to their low incidence of drug interactions, their stable plasma levels and their lack of monitoring. Rivaroxaban, a factor Xa inhibitor, has been tested in different clinical scenarios and has proved to be effective and safe, even increasing the scope of the old vitamin K antagonists...
June 4, 2018: Expert Review of Cardiovascular Therapy
Michael W Cripps, Canon C Cornelius, Paul A Nakonezny, Natalia Vazquez, Jocelyn C Wey, Peter E Gales
BACKGROUND: The use of kaolin coated dressings has become common and have efficacy in normal patients, but their increased use will inevitably include use on bleeding patients taking anticoagulants. We hypothesize that kaolin coating material (KCM) will improve clotting regardless of anticoagulation medication. METHODS: A prospective study was performed on blood from patients who were on on a vitamin K antagonist (VKA), unfractionated heparin (UH), an anti-platelet (AP) agent, a Xa inhibitor (Xa), or a direct thrombin inhibitor (DTI)...
May 30, 2018: Journal of Trauma and Acute Care Surgery
Jonathan Balakumar, Ruben Santiago, Mark Supino
Dabigatran etexilate mesylate is a direct thrombin inhibitor used for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Dabigatran belongs to a new generation of oral agents for anticoagulation - the direct oral anticoagulants (DOACs). The DOACs also include the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. In the case of major or life-threatening bleeding and/or the need for emergent invasive procedures, a reversal agent is needed if a patient is taking one of these medications...
November 2017: Clinical practice and cases in emergency medicine
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Chiara Nardin, Leopoldo Pagliani, Mario Plebani, Francesco Cinetto, Diego Guidolin, Massimo Puato, Paolo Pauletto
INTRODUCTION: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification. AIMS: to compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice...
May 30, 2018: Cardiovascular Therapeutics
Varun Kumar, Joseph Allencherril, Arthur Bracey, Alice J Chen, Wilson W Lam
Direct oral anticoagulants, which include the factor Xa inhibitor rivaroxaban, have some advantages over vitamin K antagonists in regard to stroke prevention in patients with atrial fibrillation. However, no antidotes to reverse the effect of oral anticoagulants are commercially available, which can complicate treating patients in whom reversal is urgent. We faced this challenge in a kidney transplant candidate, a 65-year-old man with end-stage renal disease who had been taking rivaroxaban for paroxysmal atrial fibrillation...
April 2018: Texas Heart Institute Journal
Michael F Bode, Alyson C Auriemma, Steven P Grover, Yohei Hisada, Alex Rennie, Weeranun D Bode, Rashi Vora, Saravanan Subramaniam, Brian Cooley, Patricia Andrade-Gordon, Silvio Antoniak, Nigel Mackman
INTRODUCTION: Rivaroxaban selectively inhibits factor Xa (FXa), which plays a central role in blood coagulation. In addition, FXa activates protease-activated receptor-2 (PAR-2). We have shown that PAR-2-/- mice exhibit less cardiac dysfunction after cardiac injury. MATERIAL AND METHODS: Wild-type (WT) and PAR-2-/- mice were subjected to left anterior descending artery (LAD) ligation to induce cardiac injury and heart failure. Mice received either placebo or rivaroxaban chow either starting at the time of surgery or 3 days after surgery and continued up to 28 days...
May 17, 2018: Thrombosis Research
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
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
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 17, 2018: International Journal of Biological Macromolecules
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