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JOURNAL ARTICLE
Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Trivendra Tripathi, Jin Zhang, Ramya Ramankutty Nair, Tutku Okyay, Kevin Zhu, Lina Abi-Mosleh
Thrombin is a key enzyme involved in blood clotting, and its dysregulation can lead to thrombotic diseases such as stroke, myocardial infarction, and deep vein thrombosis. Thrombin aptamers have the potential to be used as therapeutic agents to prevent or treat thrombotic diseases. Thrombin DNA aptamers developed in our laboratory exhibit high affinity and specificity to thrombin. In vitro assays have demonstrated their efficacy by significantly decreasing Factor II activity and increasing PT and APTT times in both plasma and whole blood...
September 7, 2023: Cells
#22
JOURNAL ARTICLE
Kazunori Toyoda, Shuji Arakawa, Masayuki Ezura, Rei Kobayashi, Yoshihide Tanaka, Shu Hasegawa, Shigeo Yamashiro, Yoji Komatsu, Yuka Terasawa, Tomohiko Masuno, Hiroshi Kobayashi, Suzuko Oikawa, Masahiro Yasaka
AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. W e aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan. METHODS: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial...
August 26, 2023: Journal of Atherosclerosis and Thrombosis
#23
JOURNAL ARTICLE
Masanobu Nagano, Kazuki Kubota, Asuka Sakata, Rei Nakamura, Toru Yoshitomi, Koji Wakui, Keitaro Yoshimoto
Heparin-induced thrombocytopenia (HIT) is a complication caused by administration of the anticoagulant heparin. Although the number of patients with HIT has drastically increased because of coronavirus disease 2019 (COVID-19), the currently used thrombin inhibitors for HIT therapy do not have antidotes to arrest the severe bleeding that occurs as a side effect; therefore, establishment of safer treatments for HIT patients is imperative. Here, we devised a potent thrombin inhibitor based on bivalent aptamers with a higher safety profile via combination with the antidote...
September 12, 2023: Molecular Therapy. Nucleic Acids
#24
JOURNAL ARTICLE
Valentin Fuhrmann, Jürgen Koscielny, Thomas Vasilakis, Tilo Andus, Adam Herber, Stefano Fusco, Elke Roeb, Ingolf Schiefke, Jonas Rosendahl, Matthias Dollinger, Karel Caca, Frank Tacke
Gastrointestinal (GI) bleeding is one of the most common complications associated with the use of direct oral anticoagulants (DOAC). Clear algorithms exist for the emergency measures in (suspected) GI bleeding, including assessing the medication history regarding anti-platelet drugs and anticoagulants as well as simple coagulation tests during pre-endoscopic management. Platelet transfusions, fresh frozen plasma (FFP), or prothrombin complex concentrate (4F-PCC) are commonly used for optimizing the coagulation status...
August 16, 2023: Zeitschrift Für Gastroenterologie
#25
JOURNAL ARTICLE
Renata de Freitas Saito, Bárbara Gomes Barion, Tania Rubia Flores da Rocha, Alex Rolband, Kirill A Afonin, Roger Chammas
Rapidly reversible anticoagulant agents have great clinical potential. Oligonucleotide-based anticoagulant agents are uniquely positioned to fill this clinical niche, as they are able to be deactivated through the introduction of the reverse complement oligo. Once the therapeutic and the antidote oligos meet in solution, they are able to undergo isothermal reassociation to form short, inactive, duplexes that are rapidly secreted via filtration by the kidneys. The formation of the duplexes interrupts the structure of the anticoagulant oligo, allowing normal coagulation to be restored...
2023: Methods in Molecular Biology
#26
REVIEW
Sana M Al-Khatib
Evidence for diagnosis and treatment of atrial fibrillation (AF) has expanded substantially since 2017, when In the Clinic last considered this subject. Direct oral anticoagulants have become the predominant therapy for thromboembolic disease, and antidotes for these drugs are now available. Device-based left atrial appendage occlusion is frequently used in patients who cannot tolerate systemic anticoagulation, and growing evidence suggests that early rhythm control improves outcomes. Catheter ablation is now frequently performed to prevent recurrent AF...
July 2023: Annals of Internal Medicine
#27
JOURNAL ARTICLE
Barbra Backus, Jan Beyer-Westendorf, Rick Body, Tobias Lindner, Martin Möckel, Vinay Sehgal, Adrian Parry-Jones, David Seiffge, Brian Gibler
An increasing number of patients presenting to the emergency department (ED) with life-threatening bleeding are using oral anticoagulants, such as warfarin, Factor IIa and Factor Xa inhibitors. Achieving rapid and controlled haemostasis is critically important to save the patient's life. This multidisciplinary consensus paper provides a systematic and pragmatic approach to the management of anticoagulated patients with severe bleeding at the ED. Repletion and reversal management of the specific anticoagulants is described in detail...
October 1, 2023: European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine
#28
JOURNAL ARTICLE
Vittorio Dalmastri, Andrea Angelini, Vera Minerva, Melissa Ballarini, Francesco Grammatico, Paola Todeschini, Attilia Maria Pizzini, Mauro Silingardi, Gaetano La Manna
BACKGROUND: Apixaban is a non-vitamin K antagonist oral anticoagulant (NOACs) recently emerged as an effective alternative to conventional vitamin K antagonists (VKAs) in the treatment of several thromboembolic disorders. However, in case of overdose or in patients requiring emergency surgery there is a high bleeding rate and severe adverse side effects due to the absence of an antidote. There is promising data from in vitro and clinical studies, that certain antithrombotic agents (that is Rivaroxaban and Ticagrelor) have been successfully removed by the extracorporeal hemoadsorption therapy CytoSorb...
July 7, 2023: Journal of Medical Case Reports
#29
JOURNAL ARTICLE
Jianfei Tu, Qing Liu, Shengye You, Zhuojun Meng, Shiji Fang, Binhong Yu, Xumin Chen, Yu Zhou, Lulu Zeng, Andreas Herrmann, Gang Chen, Jianliang Shen, Lifei Zheng, Jiansong Ji
Heparin is a widely used anticoagulant agent in the clinic. After application, its anticoagulant effect must be reversed to prevent potential side effects. Protamine sulfate (PS) is the only clinically licensed antidote that has been used for this purpose in the last 80 years, which, however, provokes severe adverse effects, such as systemic hypotension and even death. Herein, we demonstrate the potential of supercharged polypeptides as a promising alternative for protamine sulfate. A series of supercharged polypeptides with multiple positive charges was recombinantly produced, and the heparin-neutralizing performance of the polypeptides was evaluated in comparison with PS...
July 3, 2023: Biomaterials Science
#30
COMPARATIVE STUDY
Jason J Keinath, Jona Lekura, Christian D Hauser, Manisha K Bajwa, Michael E Bloome, James S Kalus, Mathew C Jones
Given the paucity of comparative efficacy data and the difference in cost between andexanet-alfa and prothrombin complex concentrates (PCC), debates continue regarding optimal cost-effective therapy for patients who present with major bleeding associated with oral factor Xa inhibitors. Available literature comparing the cost-effectiveness of the reversal agents is limited, and the large difference in price between therapy options has led many health systems to exclude andexanet-alfa from their formularies. To evaluate the clinical outcomes and cost of PCC compared to andexanet-alfa for patients with factor Xa inhibitor associated bleeds...
August 2023: Journal of Thrombosis and Thrombolysis
#31
REVIEW
Aleksandra Frackiewicz, Bartlomiej Kalaska, Joanna Miklosz, Andrzej Mogielnicki
The assessment of hemostasis is necessary to make suitable decisions on the management of patients with thrombotic disorders. In some clinical situations, for example, during thrombophilia screening, the presence of anticoagulants in sample makes diagnosis impossible. Various elimination methods may overcome anticoagulant interference. DOAC-Stop, DOAC-Remove and DOAC Filter are available methods to remove direct oral anticoagulants in diagnostic tests, although there are still reports on their incomplete efficacy in several assays...
May 19, 2023: Thrombosis Journal
#32
JOURNAL ARTICLE
Khalequz Zaman, Adi Breitman, Isa Malik, Yolanda M Fortenberry
The leading cause of death in adults in the United States is cardiovascular disease, with mortality and morbidity mainly attributed to thromboembolism. Heparin is the most common therapy used for treating venous and arterial thrombosis. Heparin effectively accelerates the inhibition of coagulation proteases thrombin and factor Xa through the serine protease inhibitor (serpin) antithrombin (AT). Heparin is an essential therapeutic anticoagulant because of its effectiveness and the availability of protamine sulfate as an antidote...
April 21, 2023: Nucleic Acid Therapeutics
#33
JOURNAL ARTICLE
Michele Romoli, Eleonora Matteo, Ludovica Migliaccio, Mauro Gentile, Maria Giulia Mosconi, Giuseppe Maria Scura, Marcello Naccarato, Enrico Colangeli, Paolo Candelaresi, Vincenzo Andreone, Fabrizio Giammello, Rosa Fortunata Musolino, Cristina Dell'Aera, Federica Nicoletta Sepe, Edoardo Pronello, Leonardo Barbarini, Marcella Caggiula, Federica Rizzo, Marco Petruzzellis, Elisa Giorli, Maria Luisa Zedde, Sabrina Anticoli, Marilena Mangiardi, Mario Muto, Francesco Diana, Maria Vittoria De Angelis, Anna Digiovanni, Letizia Concari, Sara La Gioia, Maria Sessa, Sara Biguzzi, Francesco Cordici, Marco Longoni, Maria Ruggiero, Silvia Cenciarelli, Paolo Eusebi, Simona Sacco, Valeria Caso, Maurizio Paciaroni, Stefano Ricci, Andrea Zini, Danilo Toni, David Giannandrea
INTRODUCTION: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. PATIENTS AND METHODS: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group)...
March 2023: European Stroke Journal
#34
REVIEW
Antonio Gómez-Outes, Mª Luisa Suárez-Gea, Ramón Lecumberri
PURPOSE OF REVIEW: Our objective is to describe currently available reversal agents for direct oral anticoagulants (DOACs), their target population, the available clinical practice recommendations and future directions. RECENT FINDINGS: Specific (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors) and non-specific (prothrombin complex concentrates) reversal agents are effective in neutralizing the anticoagulant effect of DOACs. New investigational antidotes such as ciraparantag and VMX-C001 offer an alternative to andexanet alfa in reversing the anticoagulant activity of direct oral factor Xa inhibitors, but more clinical data are needed before they could be licensed for use...
March 28, 2023: Current Cardiology Reports
#35
JOURNAL ARTICLE
Jan Beyer-Westendorf, Christina Köhler
The use of direct oral anticoagulants (DOACs) is increasing in patients needing treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (SPAF). This is due to the net clinical benefit in comparison to vitamin K antagonists (VKAs). The rise in DOAC use is accompanied by a remarkable reduction in heparin and VKA prescriptions. However, this rapid change in anticoagulation patterns brought new challenges to patients, prescribers, laboratories, and emergency physicians. Patients have new liberties concerning nutritional habits and comedication and no longer need frequent monitoring or dose adjustments...
February 2023: Hämostaseologie
#36
MULTICENTER STUDY
Truman J Milling, Saskia Middeldorp, Lizhen Xu, Bruce Koch, Andrew Demchuk, John W Eikelboom, Peter Verhamme, Alexander T Cohen, Jan Beyer-Westendorf, C Michael Gibson, Jose Lopez-Sendon, Mark Crowther, Ashkan Shoamanesh, Michiel Coppens, Jeannot Schmidt, Pierre Albaladejo, Stuart J Connolly
BACKGROUND: Andexanet alfa is a modified recombinant inactive factor Xa (FXa) designed to reverse FXa inhibitors. ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) was a multicenter, prospective, phase-3b/4, single-group cohort study that evaluated andexanet alfa in patients with acute major bleeding. The results of the final analyses are presented. METHODS: Patients with acute major bleeding within 18 hours of FXa inhibitor administration were enrolled...
March 28, 2023: Circulation
#37
Katharina Kneer, Adedolapo Kamaldeen Adeyemi, Jennifer Sartor-Pfeiffer, Vera Wilke, Corinna Blum, Ulf Ziemann, Sven Poli, Annerose Mengel, Katharina Feil
BACKGROUND AND AIMS: Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine...
2023: Therapeutic Advances in Neurological Disorders
#38
JOURNAL ARTICLE
Haixiang Yu, James Frederiksen, Bruce A Sullenger
In this short Perspective, we discuss the history of, and recent progress toward, the development of aptamers that can serve as rapid onset anticoagulants during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and catheter-based diagnostic and interventional procedures, several million of which are performed each year worldwide. Aptamer anticoagulants provide potent and antidote-controllable anticoagulation and have low immunogenicity. New methods of aptamer isolation and engineering have not only improved the quality of aptamers, but also accelerated their development...
January 25, 2023: RNA
#39
REVIEW
Rolf Teschke
Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous antidote treatment with N-acetylcysteine (NAC) in patients with intrinsic DILI by N-acetyl-p-aminophenol (APAP) overdose...
December 21, 2022: Biomedicines
#40
Kuan-I Lee, Jing-Hua Lin, Yen-Jung Chu, Jou-Fang Deng, Wei-Lan Chu, Dong-Zong Hung
Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a severe bleeding tendency several weeks after consuming a rice meal that was tainted with bromadiolone mistaken to be healthy food. High serum levels of bromadiolone and excessive bleeding were found in these individuals, and they needed vitamin K1 therapy for weeks. These cases indicated that long-acting anticoagulant rodenticide might induce cumulative toxicity in repeated, low-dose exposure, and the blood levels of bromadiolone might be an indicator for antidote therapy if available...
January 8, 2023: Toxics
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