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Target-specific anticoagulant

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https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#1
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632502/targeting-activated-protein-c-to-treat-hemophilia
#2
Stéphanie G I Polderdijk, Trevor P Baglin, James A Huntington
PURPOSE OF REVIEW: Hemophilia is a debilitating disease, marked by frequent, painful bleeding events, joint deterioration and early death. All current treatments consist of i.v. infusions of replacement factor or other procoagulant factors, and are incompletely effective, due in part to the short half-lives of the proteins. An alternative approach is to rebalance hemostasis by inhibiting natural anticoagulant mechanisms. In this article, we explain why activated protein C (APC) is an appropriate and safe target for the treatment of hemophilia...
June 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28629806/prevalence-of-bleeding-complications-following-ultrasound-guided-botulinum-toxin-injections-in-patiens-on-anticoagulation-or-antiplatelet-therapy
#3
Jeffrey Lavallee, Regan Royer, Geoffrey Smith
BACKGROUND: Patients on anticoagulation or antiplatelet therapy may be at higher risk of bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real time visualization of vascular structures and post-injection monitoring. Limited data exist addressing risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy...
June 16, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28618904/antiplatelet-and-antithrombotic-treatment-for-secondary-prevention-in-ischaemic-heart-disease
#4
Maddalena Lettino, Sergio Leonardi, Elia De Maria, Sigrun Halvorsen
Platelets play a key role in the pathogenesis of acute coronary syndromes and this is why antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in preventing recurrent myocardial infarction, stroke and cardiovascular death. Aspirin is the most used agent and still remains the first choice drug for lifelong administration in secondary prevention after myocardial infarction. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has significantly improved the outcome of patients with acute coronary syndromes despite an increased risk of bleeding complications...
June 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28614119/pump-priming-practices-and-anticoagulation-in-cardiac-surgery-results-from-the-global-cardiopulmonary-bypass-survey
#5
Lachlan F Miles, Timothy G Coulson, Carlos Galhardo, Florian Falter
BACKGROUND: Regional patterns of practice in cardiopulmonary bypass remain poorly understood with conflicting evidence regarding the best choices in pump priming preferences with respect to colloid and crystalloid and different types of fluid within these categories. In light of the variation in the literature, we hypothesized there would be considerable regional differences in cardiopulmonary bypass practice, particularly with respect to the type of fluid used to prime the extracorporeal circuit...
June 12, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28594360/rapid-complexation-of-aptamers-by-their-specific-antidotes
#6
Heidi Stoll, Heidrun Steinle, Nadja Wilhelm, Ludmilla Hann, Silju-John Kunnakattu, Miwako Narita, Christian Schlensak, Hans P Wendel, Meltem Avci-Adali
Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined...
June 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28594049/venous-thromboembolism-past-present-and-future
#7
Sam Schulman, Walter Ageno, Stavros V Konstantinides
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, is associated with a considerable disease burden which continues to grow along with the longer life expectancy of the population worldwide. In the past century, parenteral heparin prophylaxis was established for hospitalised patients at elevated risk of VTE. More recently, non-vitamin K antagonist oral anticoagulants (NOACs) with a direct inhibiting effect on factor Xa or thrombin, underwent extensive testing in clinical trials and have been approved for patients undergoing hip or knee replacement...
June 8, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28577959/impact-of-blood-sample-collection-methods-on-blood-protein-profiling-studies
#8
Maria Ilies, Cristina Adela Iuga, Felicia Loghin, Vishnu Mukund Dhople, Thomas Thiele, Uwe Völker, Elke Hammer
Pre-analytical factors have a significant impact on the integrity of blood samples used for qualitative and quantitative protein profiling. Important factors are the type of the blood collection tube and the anticoagulant used. Only a few studies have been performed to assess these variables by comparing only serum and EDTA plasma collection tubes with some target proteins or peptides. In this study, we investigated the protein profile of blood samples collected in serum, EDTA-, heparin-, and citrate plasma tubes...
May 31, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28500685/analysis-of-serum-markers-of-cellular-immune-activation-in-patients-with-bullous-pemphigoid
#9
Katja Bieber, Anna Lara Ernst, Stefan Tukaj, Maike M Holtsche, Enno Schmidt, Detlef Zillikens, Ralf J Ludwig, Michael Kasperkiewicz
Experimental models of bullous pemphigoid (BP), the most frequent subepidermal autoimmune bullous disease, revealed that the immune response leading to blister formation represents an incompletely understood complex process involving different inflammatory cells. In contrast to previous reports commonly focusing on limited molecular and cellular phenotypes of the disease, the aim of this study was to investigate a broad spectrum of markers of cellular immune activation in patients with BP. We found that serum levels of soluble CD4, myeloperoxidase, S100A12, eosinophil cationic protein, and soluble P-selectin were significantly elevated in patients with active BP compared with normal controls...
May 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28492296/italian-consensus-in-neuroradiological-anaesthesia-icona-managing-anaesthesia-during-endovascular-procedures
#10
Carlo A Castioni, Andrea Amadori, Federico Bilotta, Moreno Bolzon, Edoardo Barboni, Anselmo Caricato, Guido Dall'acqua, Francesco DI Paola, Andrea Forastieri Molinari, Paolo Gritti, Italia LA Rosa, Marcello Longo, Carla Maglione, Pietro Martorano, Marina Munari, Valerio Perotti, Frank Rasulo, Maria Ruggiero, Antonio Santoro, Luigia Scudeller, Miriam Tumolo, Anna T Mazzeo
Anaesthetic management of patients undergoing endovascular procedures for treating intracranial aneurysms or cerebrovascular malformations must consider a number of specific challenges, in addition to those associated with anaesthesia for other specialties. In addition to maintenance of physiological stability, manipulation of systemic and cerebral haemodynamic parameters may be required to treat any sudden unexpected catastrophic neurological events. A multidisciplinary group including neuro- and pediatric anaesthesiologists, interventional neuroradiologists, neurosurgeons, and a clinical methodologist contributed to this document...
May 11, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#11
Markus Honickel, Necib Akman, Oliver Grottke
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist (VKA) anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity)...
April 4, 2017: Shock
https://www.readbyqxmd.com/read/28450652/concordance-between-reticulocyte-hemoglobin-equivalent-and-reticulocyte-hemoglobin-content-in-ckd-patients-undergoing-hemodialysis
#12
Riadi Wirawan, Ailinda Theodora Tedja, Fify Henrika, Aida Lydia
AIM: to evaluate the correlation and the concordance between reticulocyte hemoglobin equivalent (RET-He) and reticulocyte hemoglobin content (CHr) as well as to obtain the cut-off value of RET-He as the target of iron supplementation in chronic kidney disease (CKD) patients undergoing hemodialysis. METHODS: a cross-sectional study was performed using K3EDTA-anticoagulated peripheral blood samples collected from 106 CKD patients undergoing routine hemodialysis. The samples were then analyzed using both Sysmex XN-2000 and Siemens ADVIA 2120i for RET-He and CHr analysis...
January 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28448204/future-research-opportunities-in-peri-prosthetic-joint-infection-prevention
#13
Elie Berbari, John Segreti, Javad Parvizi, Sandra I Berríos-Torres
Peri-prosthetic joint infection (PJI) is a serious complication of prosthetic joint arthroplasty. A better understanding and reversal of modifiable risk factors may lead to a reduction in the incidence of incisional (superficial and deep) and organ/space (e.g., PJI) surgical site infections (SSI). Recently, the Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) published the Guideline for Prevention of Surgical Site Infection. This targeted update applies evidence-based methodology in drafting recommendations for potential strategies to reduce the risk of SSI both across surgical procedures and specifically in prosthetic joint arthroplasty...
May 2017: Surgical Infections
https://www.readbyqxmd.com/read/28413976/laboratory-monitoring-or-measurement-of-direct-oral-anticoagulants-doacs-advantages-limitations-and-future-challenges
#14
Emmanuel J Favaloro, Leonardo Pasalic, Jennifer Curnow, Giuseppe Lippi
BACKGROUND: The Direct Oral Anticoagulants (DOACs) represent a new generation of antithrombotic agents, providing direct inhibition of either thrombin (factor IIa; FIIa) or activated factor X (FXa). Around the globe, their use is progressively rising, as these new agents replace the historical anticoagulants (heparin and vitamin K antagonists including warfarin) for various clinical conditions in medical practice. Other acronyms used to designate DOACs include TSOAC (target specific oral anticoagulants) and NOAC (novel; or non-vitamin K antagonist oral anticoagulants)...
April 17, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28412907/review-of-the-pharmacology-of-the-emerging-possibilities-of-the-direct-oral-anticoagulants-reversal
#15
Matej Samos, Lucia Stanciakova, Ingrid Skornova, Tomas Bolek, Frantisek Kovar, Jan Stasko, Peter Galajda, Marian Mokan, Peter Kubisz
BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with non-valvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients...
April 13, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28400185/purification-and-characterization-of-cc-lec-c-type-lactose-binding-lectin-a-platelet-aggregation-and-blood-clotting-inhibitor-from-cerastes-cerastes-venom
#16
Saoud Samah, Chérifi Fatah, Berjeaud Jean-Marc, Kellou-Taîri Safia, Laraba-Djebari Fatima
In this study, we reported for the first time the biochemical and structural characterization of Cc-Lec, a C-type lectin purified from Cerastes cerastes venom by affinity chromatography. This lectin was homogeneous by SDS-PAGE, and was shown to be a 34 271.59Da polypeptide by Electrospray mass spectrometry MS-ES-TOF. Its identified sequence of 160 amino acids corresponding to one subunit, revealed a high identity with other related proteins. Cc-Lec modeled 3D structure appeared as homodimer cross-linked by one disulfide bridge...
April 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28376529/role-of-direct-oral-anticoagulants-in-the-management-of-anticoagulation
#17
REVIEW
Rajiv N Thakkar, Suman W Rathbun, Scott M Wright
For decades, vitamin K antagonists (VKAs) have been the oral treatment of choice for many thromboembolic conditions. The limitations of VKAs include the need for monitoring through blood testing, drug interactions, and narrow therapeutic windows. These shortcomings have led to the development of direct oral anticoagulants. These new oral agents act on specific targets in the coagulation cascade (eg, factor Xa, thrombin) and negate some of the shortcomings of VKAs. This article reviews the roles of dabigatran, rivaroxaban, apixaban, and edoxaban in stroke prevention in nonvalvular atrial fibrillation, for prevention of venous thromboembolism after orthopedic surgery, and in the treatment of venous thromboembolism...
April 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28362634/site-selective-conjugation-of-an-anticoagulant-aptamer-to-recombinant-albumins-and-maintenance-of-neonatal-fc-receptor-binding
#18
Julie Schmøkel, Anders Voldum, Georgia Tsakiridou, Matthias Kuhlmann, Jason Cameron, Esben S Sørensen, Jesper Wengel, Kenneth A Howard
Aptamers are an attractive molecular medicine that offers high target specificity. Nucleic acid-based aptamers, however, are prone to nuclease degradation and rapid renal excretion that require blood circulatory half-life extension enabling technologies. The long circulatory half-life, predominately facilitated by engagement with the cellular recycling neonatal Fc receptor (FcRn), and ligand transport properties of albumin promote it as an attractive candidate to improve the pharmacokinetic profile of aptamers...
May 19, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28349046/venous-thromboembolism-in-critical-illness-and-trauma-pediatric-perspectives
#19
REVIEW
Ranjit S Chima, Sheila J Hanson
Critically ill children and those sustaining severe traumatic injuries are at higher risk for developing venous thromboembolism (VTE) than other hospitalized children. Multiple factors including the need for central venous catheters, immobility, surgical procedures, malignancy, and dysregulated inflammatory state confer this increased risk. As well as being at higher risk of VTE, this population is frequently at an increased risk of bleeding, making the decision of prophylactic anticoagulation even more nuanced...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28339096/pathogenesis-and-management-of-antiphospholipid-syndrome
#20
REVIEW
Deepa R J Arachchillage, Mike Laffan
Antiphospholipid antibodies are a heterogeneous group of autoantibodies that have clear associations with thrombosis and pregnancy morbidity, and which together constitute the 'antiphospholipid syndrome' (APS). However, the pathophysiology of these complications is not well understood and their heterogeneity suggests that more than one pathogenic process may be involved. Diagnosis remains a combination of laboratory analysis and clinical observation but there have been significant advances in identifying specific pathogenic features, such as domain I-specific anti-β2-glycoprotein-I antibodies...
March 24, 2017: British Journal of Haematology
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