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Warfarin reversal

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https://www.readbyqxmd.com/read/28901221/direct-oral-anticoagulant-reversal-how-when-and-issues-faced
#1
Mikhail S Dzeshka, Daniele Pastori, Gregory Y H Lip
The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. Areas covered: In the current review, risk of major bleeding in patients taking NOACs and general approaches to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed...
September 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28863196/impact-of-inr-monitoring-reversal-agent-use-heparin-bridging-and-anticoagulant-interruption-on-rebleeding-and-thromboembolism-in-acute-gastrointestinal-bleeding
#2
Naoyoshi Nagata, Toshiyuki Sakurai, Shiori Moriyasu, Takuro Shimbo, Hidetaka Okubo, Kazuhiro Watanabe, Chizu Yokoi, Mikio Yanase, Junichi Akiyama, Naomi Uemura
BACKGROUND: Anticoagulant management of acute gastrointestinal bleeding (GIB) during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB. METHODS: Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users...
2017: PloS One
https://www.readbyqxmd.com/read/28843518/management-of-factor-xa-inhibitor-associated-life-threatening-major-hemorrhage-a-retrospective-multi-center-analysis
#3
Truman J Milling, Carol L Clark, Charles Feronti, Shlee S Song, Sam S Torbati, Gregory J Fermann, Jeffrey Weiss, Dony Patel
BACKGROUND: Factor Xa (FXa) inhibitors, used for stroke prevention in atrial fibrillation and venous thromboembolism treatment and prevention, are the dominant non-Vitamin K oral anticoagulants on the market. While major bleeding may be less common with these agents compared to warfarin, it is always a risk, and little has been published on the most serious bleeding scenarios. This study describes a cohort of patients with FXa inhibitor-associated life-threatening bleeding events, their clinical characteristics, interventions and outcomes...
August 19, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28838728/perioperative-use-of-coagulation-factor-concentrates-in-patients-undergoing-cardiac-surgery
#4
REVIEW
Mark M Smith, Elena Ashikhmina, Nathan J Brinkman, David W Barbara
Coagulopathy and bleeding are common in patients undergoing cardiac surgery, with a perioperative transfusion rate in excess of 50%. The mechanism of coagulopathy associated with cardiac surgery using cardiopulmonary bypass is multifactorial. Historically, coagulation factor-mediated bleeding in such instances has been treated with allogeneic plasma transfusion. Coagulation factor concentrate use for treatment of hemophilia, congenital factor deficiencies and, more recently, emergency warfarin reversal is common...
May 10, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28833357/prothrombin-complex-concentrate-reduces-blood-product-utilization-in-heart-transplantation
#5
Daniel H Enter, Anthony L Zaki, Megan Marsh, Nikki Cool, Jane Kruse, Zhi Li, Adin-Cristian Andrei, Adam Iddriss, Patrick M McCarthy, S Chris Malaisrie, Allen Anderson, Jonathan D Rich, Duc Thinh Pham
BACKGROUND: Current practices for the reversal of warfarin prior to cardiac surgery include the use of vitamin K and fresh frozen plasma (FFP) to reduce the risk of bleeding. Although the 2010 International Society of Heart and Lung Transplantation guidelines acknowledge the use of PCC (Prothrombin Complex Concentrate), there is no clear consensus on its efficacy. The objective of this study was to assess the efficacy of 4-factor Prothrombin Complex Concentrate (4-F PCC) administration in patients requiring warfarin reversal prior to heart transplantation by determining blood product utilization perioperatively...
August 22, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28768548/the-anticoagulated-trauma-patient-in-the-age-of-the-direct-oral-anticoagulants-a-canadian-perspective
#6
Brendan Wood, Barto Nascimento, Sandro Rizoli, Michelle Sholzberg, Amanda McFarlan, Andrea Phillips, Alun D Ackery
BACKGROUND: The anticoagulated trauma patient presents a particular challenge to the critical care physician. Our understanding of these patients is defined and extrapolated by experience with patients on warfarin pre-injury. Today, many patients who would have been on warfarin are now prescribed the Direct Oral Anticoagulants (DOACs) a class of anticoagulants with entirely different mechanisms of action, effects on routine coagulation assays and approach to reversal. METHODS: Trauma registry data from Toronto's (Ontario, Canada) two Level 1 trauma centres were used to identify patients on oral anticoagulation pre-injury from June 1, 2014 to June 1, 2015...
August 2, 2017: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/28763307/comparison-of-3-factor-versus-4-factor-prothrombin-complex-concentrate-with-regard-to-warfarin-reversal-blood-product-use-and-costs
#7
Jessica DeAngelo, Daniel Jarrell, Richard Cosgrove, James Camamo, Christopher Edwards, Asad E Patanwala
BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients...
July 26, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28707821/splenic-vein-thrombosis-following-pancreas-transplantation-identification-of-factors-that-support-conservative-management
#8
J W Harbell, T Morgan, V A Feldstein, G R Roll, A Posselt, S-M Kang, S Feng, R Hirose, C E Freise, P Stock
Prophylaxis for graft portal/splenic venous thrombosis following pancreas transplant varies between institutions. Similarly, treatment of venous thrombosis ranges from early re-exploration to conservative management with anticoagulation. We wished to determine the prevalence of graft splenic vein (SV) thrombosis, as well as the clinical significance of non-occlusive thrombus observed on routine imaging. Records of 112 pancreas transplant recipients over a 5-year period at a single center were reviewed. Venous thrombosis was defined as absence of flow or presence of thrombus identified in any part of the graft SV on ultrasound...
July 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28699743/development-and-validation-of-quantitative-ultraperformance-liquid-chromatography-tandem-mass-spectrometry-assay-for-anticoagulant-rodenticides-in-liver
#9
Lori L Smith, Boying Liang, Marcia C Booth, Michael S Filigenzi, Andriy Tkachenko, Cynthia L Gaskill
Anticoagulant rodenticides (ARs) are used to control rodent populations; however, exposure to nontarget animals occurs. A sensitive and rugged quantitative method was developed, optimized, and validated for eight ARs in liver. Target analytes comprised two chemical classes: hydroxycoumarins (warfarin, coumachlor, dicoumarol, bromadiolone, brodifacoum, and difethialone) and indanediones (diphacinone and chlorophacinone). In this method, liver extracts were cleaned using dispersive solid phase extraction (d-SPE) to remove matrix interferences and analyzed by reverse phase ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)...
August 9, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28679672/the-impact-of-the-hepatocyte-to-plasma-ph-gradient-on-the-prediction-of-hepatic-clearance-and-drug-drug-interactions-for-cyp2c9-and-cyp3a4-substrates
#10
Luc Raymond Albert Rougee, Michael A Mohutsky, David W Bedwell, Kenneth J Ruterbories, Stephen D Hall
Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH is 7.0. This pH gradient can result in a pKa-dependent change in intracellular/extracellular concentrations for ionizable drugs that could affect predictions of clearance and P450 inhibition. The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated...
July 5, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28662704/thrombocytopenia-induced-by-dabigatran-two-case-reports
#11
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
https://www.readbyqxmd.com/read/28660341/low-dose-prothrombin-complex-concentrate-for-warfarin-associated-intracranial-hemorrhage-with-inr-less-than-2-0
#12
Wesley R Zemrak, Kathryn E Smith, Stephen S Rolfe, Teresa May, Robert L Trowbridge, Timothy L Hayes, Gene A Grindlinger, David B Seder
BACKGROUND: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. METHODS: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1...
June 28, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28654426/use-of-three-procoagulants-in-improving-bleeding-outcomes-in-the-warfarin-patient-with-intracranial-hemorrhage
#13
Emma P DeLoughery, Thomas G DeLoughery
: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1...
June 24, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28639882/management-of-oral-anticoagulation-therapy-after-gastrointestinal-bleeding-whether-to-when-to-and-how-to-restart-an-anticoagulation-therapy
#14
Kazuhiko Kido, Michael J Scalese
OBJECTIVE: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. DATA SOURCES: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28635130/prothrombin-complex-concentrate-for-emergent-reversal-of-warfarin-an-international-survey-of-hospital-protocols
#15
J Gorlin, S Kinney, M K Fung, A Tinmouth
For emergent warfarin reversal, four-factor prothrombin complex concentrates (4FPCCs) are recommended by many international guidelines. We surveyed international clinical sites including members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Most sites have emergent warfarin reversal protocols (53% use PCC, 25% use PCC+ plasma and 2% use plasma alone); however, variation between adjusted dosing and fixed dosing was observed.
August 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28612131/three-factor-versus-four-factor-prothrombin-complex-concentrate-for-the-emergent-management-of-warfarin-associated-intracranial-hemorrhage
#16
Daniel Fischer, Jeffrey Sorensen, Gabriel V Fontaine
BACKGROUND: Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH). METHODS: This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality...
June 13, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28604569/use-of-four-factor-prothrombin-complex-concentrate-in-the-reversal-of-warfarin-induced-and-nonvitamin-k-antagonist-related-coagulopathy
#17
Hannah Young, Jeremy L Holzmacher, Richard Amdur, Stephen Gondek, Babak Sarani, Mary E Schroeder
: To evaluate the efficacy of international normalized ratio (INR) reversal using four-factor prothrombin complex concentrate (4F-PCC) in nonmedication-induced coagulopathy. We performed a single-site, retrospective cohort study of patients receiving off-label use of 4F-PCC. Cohorts included liver dysfunction if they had acute liver decompensation or cirrhosis without other causative factors of liver failure such as sepsis, coagulopathy of acute sepsis (CAS) if they had documentation of sepsis and no underlying liver disorder, known factor deficiencies, or medication-induced coagulopathy, or warfarin if they were taking warfarin...
June 9, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28594426/new-developments-in-anticoagulants-past-present-and-future
#18
Jeffrey I Weitz, Job Harenberg
Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients...
June 28, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#19
Truman J Milling, Jennifer Frontera
Thrombosis is a leading cause of morbidity and mortality in the United States. Arterial and venous thromboses are implicated in the pathogenesis of major disorders, including myocardial infarction, ischemic stroke, and venous thromboembolism. Over the past decade, direct oral anticoagulants (DOACs) (eg, direct thrombin inhibitor and factor Xa [FXa] inhibitors) have been adopted as alternatives to warfarin due to their clinical advantages and efficacy for the treatment of thrombosis. As with all anticoagulants, treatment with DOACs is associated with a risk of major bleeding, including life-threatening gastrointestinal bleeds and intracranial hemorrhages (ICHs)...
April 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28575123/induction-of-axial-chirality-in-divanillin-by-interaction-with-bovine-serum-albumin
#20
Diego Venturini, Aguinaldo Robinson de Souza, Ignez Caracelli, Nelson Henrique Morgon, Luiz Carlos da Silva-Filho, Valdecir Farias Ximenes
Vanillin is a plant secondary metabolite and has numerous beneficial health applications. Divanillin is the homodimer of vanillin and used as a taste enhancer compound and also a promissory anticancer drug. Here, divanillin was synthesized and studied in the context of its interaction with bovine serum albumin (BSA). We found that divanillin acquires axial chirality when complexed with BSA. This chiroptical property was demonstrated by a strong induced circular dichroism (ICD) signal. In agreement with this finding, the association constant between BSA and divanillin (3...
2017: PloS One
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