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oral direct thrombin inhibitors

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https://www.readbyqxmd.com/read/28921890/phase-ii-study-of-dabigatran-in-children-with-venous-thrombosis-pharmacokinetics-safety-and-tolerabilty
#1
J M L Halton, M Albisetti, B Biss, L Bomgaars, M Brueckmann, S Gropper, R Harper, F Huang, M Luciani, H Maas, I Tartakovsky, L G Mitchell
BACKGROUND: The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations. Dabigatran etexilate (DE), a direct thrombin inhibitor, may offer an alternative therapeutic option. OBJECTIVES: To assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of DE oral liquid formulation (OLF) in pediatric patients with VTE. PATIENTS/METHODS: Patients who had completed planned treatment with low-molecular-weight heparin or oral anticoagulants for VTE were enrolled in two age groups (2-<12 and 1-<2 years) and received DE OLF based on an age- and weight-adjusted nomogram...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28910988/anticoagulation-after-coronary-stenting-a-systemic-review
#2
Zhe Dong, Jingang Zheng
Introduction or background: Anticoagulant therapy is mainly used to prevent patients from suffering coronary and systemic thromboembolism after stenting. Many studies have been done to formulate an optimized regimen of a post-PCI or long-time anticoagulant therapy. Recent advances in the selection and duration of anticoagulant agents will be conducive to the management of patients who are considered to need anticoagulant therapy after stenting. Sources of data: Key recent published literature, including international guidelines and relevant reviews...
September 1, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28878572/dabigatran-reversal-with-idarucizumab-in-a-patient-undergoing-heart-transplantation-first-european-report
#3
António Tralhão, Carlos Aguiar, Jorge Ferreira, Maria José Rebocho, Emília Santos, Dinis Martins, José Pedro Neves
BACKGROUND: Dabigatran is a direct thrombin inhibitor with a favorable effectiveness and safety profile when compared to vitamin K antagonists, both in randomized trials and real world registries of atrial fibrillation patients. Yet, physicians' fear of high bleeding risk scenarios in daily clinical practice still precludes a more widespread use of oral anticoagulation. We hereby report a successful case of dabigatran reversal with the novel monoclonal antibody fragment idarucizumab in a patient undergoing heart transplantation...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28856946/spontaneous-hit-syndrome-post-knee-replacement-surgery-with-delayed-recovery-of-thrombocytopenia-a-case-report-and-literature-review
#4
Dilli Ram Poudel, Sushil Ghimire, Rashmi Dhital, Daniel A Forman, Theodore E Warkentin
Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10(9)/L...
September 2017: Platelets
https://www.readbyqxmd.com/read/28856671/direct-oral-anticoagulant-medications-in-calciphylaxis
#5
Brian J King, Rokea A El-Azhary, Marian T McEvoy, Raymond C Shields, Robert D McBane, James T McCarthy, Mark D P Davis
BACKGROUND: Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. METHODS: We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants...
August 30, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28808918/idarucizumab-in-dabigatran-treated-patients-with-acute-ischemic-stroke-receiving-alteplase-a-systematic-review-of-the-available-evidence
#6
REVIEW
Slaven Pikija, Laszlo K Sztriha, J Sebastian Mutzenbach, Stefan M Golaszewski, Johann Sellner
BACKGROUND AND PURPOSE: Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke...
August 14, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28808596/the-severity-of-intracranial-hemorrhages-measured-by-free-hemoglobin-in-the-brain-depends-on-the-anticoagulant-class-experimental-data
#7
Kyle M Ware, Douglas L Feinstein, Israel Rubinstein, Prudhvi Battula, Jose Otero, Lee Hebert, Tzu-Fei Wang, Alexandra Ivanova, Shweta Chaudhary, Jessica Hemminger, Sergey V Brodsky
Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor)...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28805310/use-of-direct-oral-anticoagulants-for-stroke-prevention-in-elderly-patients-with-nonvalvular-atrial-fibrillation
#8
Lynn B Oertel, Annemarie E Fogerty
BACKGROUND AND PURPOSE: Four direct oral anticoagulants (DOACs) are available for the prevention of stroke in nonvalvular atrial fibrillation (NVAF): dabigatran (a direct thrombin inhibitor); and rivaroxaban, apixaban, and edoxaban (factor Xa inhibitors). This article summarizes the safety and efficacy of DOACs for the prevention of stroke in elderly NVAF patients. METHODS: PubMed was searched to identify published results of randomized, controlled trials evaluating DOACs for stroke prevention in elderly NVAF patients...
September 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/28805299/dissociation-between-the-pharmacokinetics-and-pharmacodynamics-of-once-daily-rivaroxaban-and-twice-daily-apixaban-a-randomized-crossover-study
#9
Reinhold Kreutz, Pontus B Persson, Dagmar Kubitza, Kirstin Thelen, Stefan Heitmeier, Stephan Schwers, Michael Becka, Melanie Hemmrich
BACKGROUND: The anticoagulant actions of the oral direct factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. OBJECTIVES: To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in nonvalvular atrial fibrillation. METHODS: Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32)...
August 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28804832/measuring-direct-oral-anticoagulants
#10
Robert C Gosselin, Jonathan Douxfils
Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28790786/direct-acting-oral-anticoagulant-bench-to-bedside
#11
REVIEW
D S Chadha, P Bharadwaj
Vitamin K antagonists are an effective group of oral anticoagulants. However because of genetic variability in their metabolism and multiple food and drug interactions, these drugs have narrow therapeutic window with unpredictable anticoagulant effects requiring constant monitoring. Several newer direct acting oral anticoagulants have been approved for prevention of stroke in patients with nonvalvular atrial fibrillation and treatment or prevention of venous thromboembolism. The direct acting oral anticoagulants include the direct thrombin inhibitor (dabigatran) and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban)...
July 2017: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28769570/reversal-of-direct-oral-anticoagulants
#12
REVIEW
Mosaad Almegren
Reversal agents for direct oral anticoagulants (DOACs), including factor X inhibitors and direct thrombin inhibitors, are a major concern in clinical practice. After DOACs were introduced and became widely used as an alternative for vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation, the need for effective reversal agents has increased, particularly for life-threatening bleeding episodes related to DOACs or to reverse medication effects during urgent interventions...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28768967/dabigatran-therapy-resulting-in-the-resolution-of-rivaroxaban-resistant-left-atrial-appendage-thrombi-in-patients-with-atrial-fibrillation
#13
Tetsuya Watanabe, Yukinori Shinoda, Kuniyasu Ikeoka, Tomoko Minamisaka, Hidetada Fukuoka, Hirooki Inui, Shiro Hoshida
Patients with persistent atrial fibrillation (AF) and a large left atrium are at a high risk for thromboembolisms. Recently, direct oral anticoagulants (DOACs) have mainly been used for the prevention of cardiac embolisms caused by AF. Transesophageal echocardiography (TEE) is performed in order to exclude any left atrial appendage (LAA) thrombi. We herein report two cases of persistent AF, both of which were treated with rivaroxaban for more than two years. Since TEE identified mobile LAA thrombi with this treatment, we switched from rivaroxaban to the direct thrombin inhibitor dabigatran...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28761683/mortality-and-oral-anticoagulants-in-the-food-and-drug-administration-adverse-event-reporting-system
#14
Victor Serebruany, Vasily Cherepanov, Seth Fortmann, Moo Hyun Kim
OBJECTIVE: The comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. METHODS: We selected CDR from the FAERS database linked to four NOACs and warfarin...
2017: Open Heart
https://www.readbyqxmd.com/read/28740848/patient-characteristics-and-clinical-outcomes-with-low-dose-dabigatran
#15
Ramin Ebrahimi, Janet K Han, Seung H Goe, Michelle Treadwell, Zenaida Feliciano
BACKGROUND/AIMS: Dabigatran, an oral direct thrombin inhibitor, is used in patients with non-valvular atrial fibrillation to reduce thromboembolic events. Whereas the 150 mg dosing regimen has been extensively studied in clinical setting, to date, there is no clinical data on the 75 mg (low dose, "LD") regimen. In this study, we evaluated patient characteristics and clinical outcomes in 49 patients treated with LD dabigatran. METHODS: Electronic medical records were utilized to compare patients from one medical center treated with LD dabigatran to those from the warfarin arm of the RE-LY trial...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28704111/incomplete-dabigatran-reversal-with-idarucizumab
#16
Aaron P Steele, Jin A Lee, William E Dager
CONTEXT: With increasing use of direct oral anticoagulants (DOACs), urgent reversal of these agents becomes a growing concern. Idarucizumab is a humanized monoclonal antibody fragment that specifically binds to dabigatran with higher affinity than thrombin, rapidly neutralizing its anticoagulant effect without increased risk of thrombosis. CASE DETAILS: We describe two cases in which the recommended dose of idarucizumab was unsuccessful in completely reversing the anticoagulant effects of dabigatran...
July 13, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28703014/thrombin-receptor-agonist-peptide-induced-platelet-aggregation-is-reduced-in-patients-receiving-dabigatran
#17
Frantisek Nehaj, Juraj Sokol, Michal Mokan, Jela Ivankova, Maros Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in thrombosis management. The direct thrombin inhibitor dabigatran seems to obstruct tenase complex by inhibiting thrombin generated in the initial phase and feed back to the amplification phase of cell-based coagulation reactions. However, it is still not fully understood if and how dabigatran impact platelet function. This observational study aimed to assess in vitro platelet function in patients with atrial fibrillation receiving dabigatran...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28689334/safety-and-interactions-of-direct-oral-anticoagulants-with-antiarrhythmic-drugs
#18
REVIEW
Ipek Celikyurt, Christoph R Meier, Michael Kühne, Beat Schaer
Direct oral anticoagulants (DOACs) are novel direct-acting medications that are selective for either thrombin or activated factor X. Due to their obvious benefits for patients (fewer interactions, broader therapeutic window, etc.), they are increasingly used as an alternative to warfarin, phenprocoumon, or acenocoumarol. One of the major indications for use of DOACs is stroke prevention in patients with atrial fibrillation (AF). However, interactions still exist, especially in combination with antiarrhythmic drugs (AADs), which are frequently given to AF patients for rhythm or rate control...
July 8, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28671072/anticoagulant-activity-of-oral-rivaroxaban-in-healthy-dogs
#19
B Conversy, M C Blais, M Dunn, C Gara-Boivin, J R E Del Castillo
Rivaroxaban is an oral, direct factor Xa inhibitor used in human thrombotic disorders. In view of the in vitro concentration dependent anticoagulant effects of rivaroxaban in dogs, the time course of its anticoagulant effects was characterized in healthy dogs. Twenty-four healthy Beagles were randomized into three groups (n = 8 per group) and received orally either a placebo or 20 mg rivaroxaban once or twice at an 8 h interval. Fifteen blood samples were collected over a 30 h period, and blindly assayed for prothrombin time (PT), activated partial thromboplastin time (aPTT), tissue factor induced thrombin generation (TG) and anti-factor Xa activity...
May 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28662704/thrombocytopenia-induced-by-dabigatran-two-case-reports
#20
Hyun Goo Kang, Seung Jae Lee, Ji Yeon Chung, Jin Sung Cheong
BACKGROUND: Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin...
June 29, 2017: BMC Neurology
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