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Direct thrombin inhibitor

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https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#1
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910004/dabigatran-overdose-a-case-report-of-acute-hepatitis-extracorporeal-treatment
#2
Mariagrazia Porru, Antonella Mameli, Maria E Cianchetti, Mario Musu, Paola Schirru, Maria F Ruberto, Doris Barcellona, Francesco Marongiu
Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration...
December 1, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27909544/reducing-the-risk-of-stroke-in-patients-with-nonvalvular-atrial-fibrillation-with-direct-oral-anticoagulants-is-one-of-these-not-like-the-others
#3
REVIEW
Paul P Dobesh Pharm D, John Fanikos Mba R Ph
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27904902/a-novel-hirudin-derivative-inhibiting-thrombin-without-bleeding-for-subcutaneous-injection
#4
Bing Zhao, Yanling Zhang, Yinong Huang, Jinchao Yu, Yaran Li, Qi Wang, Yixin Ma, Hou-Yan Song, Min Yu, Wei Mo
Currently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#5
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27901390/effects-of-various-antiplatelet-drugs-on-ex-vivo-platelet-activation-induced-by-equine-herpesvirus-type-1
#6
Daniela Hernandez, Wee Ming Yeo, Marjory B Brooks, Sally L Ness, Thomas J Divers, Tracy Stokol
OBJECTIVE To evaluate the effects of treatment of horses with standard platelet inhibitors on ex vivo inhibition of platelet activation by equine herpesvirus type I (EHV-I). ANIMALS II healthy adult horses. PROCEDURES In a double-blinded, placebo-controlled crossover study, horses were treated orally for 5 days with theophylline (5 mg/kg, q 12 h), pentoxifylline (10 mg/kg, q 12 h), clopidogrel bisulfate (4 mg/kg, q 24 h), acetylsalicylic acid (20 mg/kg, q 24 h), or placebo. Horses received all treatments, each separated by a 3-week washout period...
December 2016: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/27900867/-new-direct-oral-anticoagulants-actual-review
#7
Jana Michalcová, Miroslav Penka, Alena Buliková, Jiřina Zavřelová, Andrea Štěpařová
In recent years the options of anticoagulant/antithrombotic therapy have extended with new - direct oral anticoagulants, comprising direct thrombin inhibitors (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban). These agents represent another progress towards "the ideal antithrombotic drug", and thus towards a safe and effective antithrombotic therapy. The following article provides actual review and recommendations for clinical practice, including laboratory assessment and management of emergency situations...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27896543/vitamin-k-antagonists-relative-strengths-and-weaknesses-vs-direct-oral-anticoagulants-for-stroke-prevention-in-patients-with-atrial-fibrillation
#8
REVIEW
Andreas Zirlik, Christoph Bode
Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents-the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]-have been approved for these and other indications...
November 28, 2016: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/27895055/role-of-agents-for-reversing-the-effects-of-target-specific-oral-anticoagulants
#9
REVIEW
Tanya R Riley, Mary L Gauthier-Lewis, Chelsea K Sanchez, Janine S Douglas
PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results...
November 28, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27888761/tissue-thrombin-is-associated-with-the-pathogenesis-of-dilated-cardiomyopathy
#10
Keiichi Ito, Kenichi Hongo, Taro Date, Masahiro Ikegami, Hiroshi Hano, Mamiko Owada, Satoshi Morimoto, Yusuke Kashiwagi, Daisuke Katoh, Takuya Yoshino, Akira Yoshii, Haruka Kimura, Tomohisa Nagoshi, Ichige Kajimura, Yoichiro Kusakari, Toru Akaike, Susumu Minamisawa, Kazuo Ogawa, Kosuke Minai, Takayuki Ogawa, Makoto Kawai, Junji Yajima, Seiichiro Matsuo, Teiichi Yamane, Ikuo Taniguchi, Sachio Morimoto, Michihiro Yoshimura
BACKGROUND: Thrombin is a serine protease known to be the final product of the coagulation cascade. However, thrombin plays other physiological roles in processes such as gastric contractions and vessel wound healing, and a state of coagulability is increased in patients with dilated cardiomyopathy (DCM). In this study, we investigate the role of thrombin in the pathogenesis of DCM. The purpose of this study is to clarify the role of thrombin in the pathogenesis of DCM and investigate the possibility of treatment against DCM by thrombin inhibition...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27866948/pulmonary-embolism-rates-following-total-hip-arthroplasty-with-prophylactic-anticoagulation-some-pulmonary-emboli-cannot-be-avoided
#11
Jay R Lieberman, Vincent Cheng, Mark P Cote
BACKGROUND: A symptomatic pulmonary embolism (PE) after total joint arthroplasty has been described as a "never event." Despite potent anticoagulants and improvements in patient care, PE continues to occur following total hip arthroplasty (THA). This study evaluates symptomatic PE rates over time in THA patients enrolled in multicenter randomized clinical trials (RCTs) assessing the efficacy of venous thromboembolism prophylaxis regimens. METHODS: The MEDLINE and Cochrane Central Register of Controlled Trials were searched to identify clinical trials assessing prophylactic anticoagulation in patients undergoing THA between January 1995 and December 2015...
September 28, 2016: Journal of Arthroplasty
https://www.readbyqxmd.com/read/27861293/organ-pretreatment-with-cytotopic-endothelial-localizing-peptides-to-ameliorate-microvascular-thrombosis-and-perfusion-deficits-in-ex-vivo-renal-hemoreperfusion-models
#12
Karim Hamaoui, Sally Gowers, Martyn Boutelle, Terry H Cook, George Hanna, Ara Darzi, Richard Smith, Anthony Dorling, Vassilios Papalois
BACKGROUND: Hypothermic machine organ perfusion (HMP) offers opportunity to manipulate grafts with pharmacological agents prior to transplantation. Pretreating organs with novel cytotopic anticoagulant peptides that localize to endothelial cell membranes could ameliorate microvascular thrombotic sequelae posttransplantation. We describe experiments testing thrombalexin (TLN), a novel cell binding thrombin inhibitor, using porcine and unused human kidneys in a series of ex vivo normothermic hemoreperfusion models...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27852034/thrombin-inhibition-and-cisplatin-block-tumor-progression-in-ovarian-cancer-by-alleviating-the-immunosuppressive-microenvironment
#13
Eric T Alexander, Allyson R Minton, Molly C Peters, Joanne van Ryn, Susan K Gilmour
Cancer is often associated with an increased risk of thrombotic complications which can be aggravated by treatment with chemotherapeutics such as cisplatin. Multiple lines of evidence suggest that thrombin activity promotes tumor growth and metastasis. We examined the effect of co-treatment with dabigatran etexilate, a direct thrombin inhibitor, and cisplatin using the murine ID8 ovarian cancer model. Mice receiving co-treatment with both dabigatran etexilate and low dose cisplatin had significantly smaller tumors, developed less ascites and had lower levels of circulating activated platelets and tissue factor (TF) positive microparticles than those treated with dabigatran etexilate or cisplatin alone...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832560/the-effect-of-dabigatran-on-the-kaolin-activated-whole-blood-thromboelastogram
#14
A 'Aho, K Byrne
Dabigatran is a direct thrombin inhibitor, which is increasingly likely to be encountered in patients presenting for surgery. This study examines whether there is a consistent effect of dabigatran on the thromboelastogram (TEG) and whether this correlates with the effects of dabigatran on traditional coagulation parameters. Twenty patients taking dabigatran had blood sampled for kaolin-activated whole blood TEG analysis and routine coagulation testing. There was a statistically significant correlation between thrombin clotting time (TCT) and R-time (R=0...
November 2016: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/27797449/idarucizumab-for-reversal-of-dabigatran-prior-to-acute-surgery-a-schematic-approach-based-on-a-case-report
#15
Lene Rosenberg, Gustav Gerstrøm, Mads Nybo
Dabigatran, an oral direct thrombin inhibitor, is frequently used in treatment of venous thromboembolism and prevention of stroke in non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment that reverses the dabigatran effect, was introduced to the market to be used in case of life-threatening bleeding or acute surgery/invasive procedures. Whether usage should be guided by measurement of plasma dabigatran and/or other coagulation parameters is, however, still uncertain. We here describe the use of idarucizumab prior to acute surgery in a patient on dabigatran and acetylsalicylic acid...
October 31, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27792070/a-review-on-the-reversal-of-the-old-and-new-anticoagulants
#16
Abby Mynatt Bailey, Matthew C Blackburn, John M Crowley, Kari S Horn, Amy E Schultz, Stephanie Baker Justice
It is not uncommon for providers in the emergency department to take care of patients who are taking anticoagulant therapy in the outpatient setting. However, the bigger challenge is caring for these patients when they present with bleeding that could be secondary to 1 or more of these medications. In recent years, this class of medications has expanded from warfarin to include direct thrombin inhibitors and Factor Xa inhibitors. As this class of medications has evolved, so has the approach to the reversal of these agents...
October 2016: Advanced Emergency Nursing Journal
https://www.readbyqxmd.com/read/27766804/stroke-prevention-in-atrial-fibrillation-which-is-the-best-balanced-in-efficacy-and-safety-as-a-thromboprophylactic
#17
Viraj Suvarna
Stroke prevention in atrial fibrillation (AF) has reached an exciting phase with a plethora of newer, potentially more efficacious and safer agents being introduced for physicians to select from. Dabigatran belongs to a class of anticoagulants called direct thrombin inhibitors, while rivaroxaban, apixaban, and edoxaban are direct Factor Xa inhibitors. Purely from a therapeutic endpoint perspective-based on the action of anticoagulants in reducing cardioembolic stroke-in clinical trials, one should look at whether a new anticoagulant in patients with AF prevents ischemic stroke...
October 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27765812/direct-thrombin-inhibitor-for-lvad-thrombosis-a-closer-look
#18
Jessica Rimsans, Katelyn W Sylvester, Jean M Connors
Available options for the treatment of advanced heart failure have expanded to include the use of mechanical circulatory assist devices to improve quality of life in those both eligible and ineligible for heart transplant. Although there have been significant advancements in device technologies, anticoagulation protocols, and multidisciplinary team management, bleeding and thrombosis are the most common adverse effects. Management strategies for pump thrombosis and their outcomes vary considerably among mechanical circulatory support centers and include intensification of antithrombotic therapy (medical) and device exchange (surgical)...
October 7, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27752290/reversal-of-direct-oral-anticoagulants-in-hemophilia-treatment-ash-meeting-2015
#19
Clemens Feistritzer, Stefan Schmidt
During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted...
2016: Memo
https://www.readbyqxmd.com/read/27747056/risk-guided-use-of-the-direct-thrombin-inhibitor-bivalirudin-insights-from-recent-trials-and-analyses
#20
COMMENT
William B Hillegass, Gregory S Bradford
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
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