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https://www.readbyqxmd.com/read/28913813/pharmacotherapy-pearls-for-emergency-neurological-life-support
#1
Gretchen M Brophy, Theresa Human
The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient's organ function and medication allergies, potential adverse drug effects, drug interactions and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials...
September 14, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28913672/reversal-of-dabigatran-associated-bleeding-using-idarucizumab-review-of-the-current-evidence
#2
REVIEW
Michela Giustozzi, Melina Verso, Giancarlo Agnelli, Cecilia Becattini
Major bleeding occurs in about 4% of patients while on treatment with direct oral anticoagulants (DOACs). The case-fatality rate associated with these events is estimated to be about 5%. The specific roles of antidotes, when used with DOACs in reducing the case fatality or improving the overall clinical course of these events, are not thoroughly understood. To this regard, the US Food and Drug Administration as well as European Medicines Agency have recently licensed idarucizumab for the management of patients with life-threatening bleeding or the need for urgent surgery/procedures while on treatment with dabigatran...
September 14, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28904343/engineered-factor-xa-variants-retain-procoagulant-activity-independent-of-direct-factor-xa-inhibitors
#3
Daniël Verhoef, Koen M Visscher, C Ruben Vosmeer, Ka Lei Cheung, Pieter H Reitsma, Daan P Geerke, Mettine H A Bos
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28901221/direct-oral-anticoagulant-reversal-how-when-and-issues-faced
#4
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/28887767/management-of-spontaneous-intracerebral-hemorrhage
#5
REVIEW
Roland Veltkamp, Jan Purrucker
PURPOSE OF REVIEW: We review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH). RECENT FINDINGS: Therapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH...
September 8, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28880550/a-polymer-therapeutic-having-universal-heparin-reversal-activity-molecular-design-and-functional-mechanism
#6
Manu Thomas Kalathottukaren, Srinivas Abbina, Kai Yu, Rajesh A Shenoi, A Louise Creagh, Charles Haynes, Jayachandran N Kizhakkedathu
Heparins are widely used to prevent blood clotting during surgeries and for the treatment of thrombosis. However, bleeding associated with heparin therapy is a concern. Protamine, the only approved antidote for unfractionated heparin (UFH) could cause adverse cardiovascular events. Here, we describe a unique molecular design used in the development of a synthetic dendritic polycation named as Universal Heparin Reversal Agent (UHRA), an antidote for all clinically used heparin anticoagulants. We elucidate the mechanistic basis for the selectivity of UHRA to heparins and its non-toxic nature...
September 7, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28878572/dabigatran-reversal-with-idarucizumab-in-a-patient-undergoing-heart-transplantation-first-european-report
#7
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/28878012/synthetic-oligosaccharides-can-replace-animal-sourced-low-molecular-weight-heparins
#8
Yongmei Xu, Kasemsiri Chandarajoti, Xing Zhang, Vijayakanth Pagadala, Wenfang Dou, Debra Moorman Hoppensteadt, Erica M Sparkenbaugh, Brian Cooley, Sharon Daily, Nigel S Key, Diana Severynse-Stevens, Jawed Fareed, Robert J Linhardt, Rafal Pawlinski, Jian Liu
Low-molecular weight heparin (LMWH) is used clinically to treat clotting disorders. As an animal-sourced product, LMWH is a highly heterogeneous mixture, and its anticoagulant activity is not fully reversible by protamine. Furthermore, the reliability of the LMWH supply chain is a concern for regulatory agencies. We demonstrate the synthesis of heparin dodecasaccharides (12-mers) at the gram scale. In vitro experiments demonstrate that the anticoagulant activity of the 12-mers could be reversed using protamine...
September 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28867804/fviia-stf-and-thrombin-inhibitory-activities-of-compounds-isolated-from-microcystis-aeruginosa-k-139
#9
Andrea Roxanne J Anas, Akane Mori, Mineka Tone, Chiaki Naruse, Anna Nakajima, Hirohiko Asukabe, Yoshiaki Takaya, Susumu Y Imanishi, Tomoyasu Nishizawa, Makoto Shirai, Ken-Ichi Harada
The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction...
August 30, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28867189/modified-high-throughput-quantification-of-plasma-micrornas-in-heparinized-patients-with-coronary-artery-disease-using-heparinase
#10
Sufang Li, Feng Zhang, Yuxia Cui, Manyan Wu, Chongyou Lee, Junxian Song, Chengfu Cao, Hong Chen
Heparin, a widely used anticoagulant in cardiovascular diseases, is notorious for its inhibitory effect on qRT-PCR-based detection. Heparinase I could degrade heparin in RNA. qRT-PCR-based TaqMan Low Density Array (TLDA) technology is commonly used for circulating microRNAs (miRNAs) profiling analysis. However, the effect of heparin contamination on inhibition of miRNAs TLDA amplification, as well as the method for removing heparin during this process, are not yet well investigated. We obtained the plasma RNA samples from patients undergoing percutaneous coronary intervention (PCI) before and after heparinization (n = 26)...
September 1, 2017: Biochemical and Biophysical Research Communications
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
#11
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/28857806/reversing-dabigatran-anticoagulation-with-prothrombin-complex-concentrate-versus-idarucizumab-as-part-of-multimodal-hemostatic-intervention-in-an-animal-model-of-polytrauma
#12
Markus Honickel, Till Braunschweig, Rolf Rossaint, Christian Stoppe, Hugo Ten Cate, Oliver Grottke
BACKGROUND: Although idarucizumab is the preferred treatment for urgent dabigatran reversal, it is not always available. Prothrombin complex concentrate (PCC) may be an alternative and, with bleeding in trauma, additional hemostatic therapy may be required. The authors investigated multimodal treatment in a preclinical polytrauma model. METHODS: Dabigatran etexilate (30 mg/kg twice daily) was given orally to 45 male pigs for 3 days. On day 4, animals received a dabigatran infusion before blunt liver injury and bilateral femur fractures...
August 30, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28846831/reversal-of-apixaban-anticoagulation-by-4-factor-prothrombin-complex-concentrates-in-healthy-subjects-a-randomized-3-period-crossover-study
#13
Yan Song, Zhaoqing Wang, Itay Perlstein, Jessie Wang, Frank LaCreta, Robert J A Frost, Charles Frost
BACKGROUND: Currently, there is no approved reversal agent for direct factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). OBJECTIVE: This open-label, randomized, placebo-controlled, 3-period crossover study assessed the effect of two 4-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. METHODS: Subjects received apixaban 10 mg twice daily for 3 days...
August 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28843518/management-of-factor-xa-inhibitor-associated-life-threatening-major-hemorrhage-a-retrospective-multi-center-analysis
#14
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/28828368/inhalation-therapies-in-acute-respiratory-distress-syndrome
#15
REVIEW
Antonio Artigas, Marta Camprubí-Rimblas, Neus Tantinyà, Josep Bringué, Raquel Guillamat-Prats, Michael A Matthay
The defining features of acute respiratory distress syndrome (ARDS) are an excessive inflammatory respiratory response associated with high morbidity and mortality. Treatment consists mainly of measures to avoid worsening lung injury and cannot reverse the underlying pathophysiological process. New pharmacological agents have shown promising results in preclinical studies; however, they have not been successfully translated to patients with ARDS. The lack of effective therapeutic interventions has resulted in a recent interest in strategies to prevent ARDS with treatments delivering medications directly to the lungs by inhalation and nebulization, hopefully minimizing systemic adverse events...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28810116/stop-the-bleeding-reversing-the-effects-of-direct-acting-oral-anticoagulants
#16
Janet Fischer
No abstract text is available yet for this article.
November 2016: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28808918/idarucizumab-in-dabigatran-treated-patients-with-acute-ischemic-stroke-receiving-alteplase-a-systematic-review-of-the-available-evidence
#17
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/28806993/successful-intravenous-thrombolysis-for-ischemic-stroke-after-reversal-of-dabigatran-anticoagulation-with-idarucizumab-a-case-report
#18
Sergio Agosti, Laura Casalino, Enrico Rocci, Gabriele Zaccone, Eugenia Rota
BACKGROUND: Non-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment for immediate reversal of dabigatran-induced anticoagulation, has been introduced into the market to be used in life-threatening bleeding or urgent surgery, allowing for rapid normalization of clotting parameters. The use of idarucizumab is not yet well established in patients presenting with acute ischemic stroke on dabigatran who are candidates for thrombolytic therapy...
August 15, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28802751/acute-management-of-hemostasis-in-patients-with-neurological-injury
#19
REVIEW
M Irem Baharoglu, Anneke Brand, Maria M Koopman, Marinus Vermeulen, Yvo B W E M Roos
Neurological injuries can be divided into those with traumatic and nontraumatic causes. The largest groups are traumatic brain injury (TBI) and nontraumatic stroke. TBI patients may present with intracranial hemorrhages (contusions, or subdural or epidural hematomas). Strokes are ischemic or hemorrhagic. In all these disorders, thrombosis and hemostasis play a major role. Treatment aims to either cease bleeding and/or restore perfusion. We reviewed hemostatic and thrombolytic therapies in patients with neurological injuries by MEDLINE and EMBASE search using various key words for neurological disorders and hemostatic therapies restricted to English language and human adults...
July 13, 2017: Transfusion Medicine Reviews
https://www.readbyqxmd.com/read/28800457/fucosylated-chondroitin-sulfate-oligosaccharides-exert-anticoagulant-activity-by-targeting-at-intrinsic-tenase-complex-with-low-fxii-activation-importance-of-sulfation-pattern-and-molecular-size
#20
Junhui Li, Shan Li, Lufeng Yan, Tian Ding, Robert J Linhardt, Yanlei Yu, Xinyue Liu, Donghong Liu, Xingqian Ye, Shiguo Chen
Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs...
July 28, 2017: European Journal of Medicinal Chemistry
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