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Antithrombin 3

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https://www.readbyqxmd.com/read/29315844/local-and-systemic-coagulation-marker-response-to-musculocutaneous-flap-ischemia-reperfusion-injury-and-remote-ischemic-conditioning-an-experimental-study-in-a-porcine-model
#1
Andreas Engel Krag, Christine Lodberg Hvas, Birgitte Jul Kiil, Gete Toft Eschen, Tine Engberg Damsgaard, Anne-Mette Hvas
BACKGROUND: Remote ischemic conditioning (RIC) administered by non-lethal periods of extremity ischemia and reperfusion attenuates ischemia-reperfusion injury. We aimed to investigate the local and systemic coagulation marker response to flap ischemia-reperfusion injury, and the effects of RIC on coagulation markers following flap ischemia-reperfusion injury. METHODS: A musculocutaneous latissimus dorsi flap was subjected to 4 h of ischemia followed by 7 h of reperfusion in 16 female Danish Landrace pigs (39 kg)...
January 8, 2018: Microsurgery
https://www.readbyqxmd.com/read/29308659/thrombophilia-associated-factors-in-patients-with-spontaneous-osteonecrosis-of-the-knee
#2
Niv Marom, Jonathan Ej Koch, Yiftah Beer, Martin Ellis, Gil Ganot, Meir Nyska, Guy Maoz, Iftach Hetsroni
Objective To test whether patients with spontaneous osteonecrosis of the knee (SONK) are characterized by abnormal levels of thrombophilia-associated factors. Design Twenty-five patients with SONK were recruited. Inclusion criteria were (1) age >40 years, (2) acute onset knee pain not precipitated by trauma, and (3) MRI findings consistent with SONK. Exclusion criteria were (1) history of cancer and chemotherapy and (2) factors associated with secondary osteonecrosis. Blood tests included 13 thrombophilia-associated factors that were either heritable mutations or acquired factors...
January 1, 2018: Cartilage
https://www.readbyqxmd.com/read/29228388/caspase-inhibition-reduces-hepatic-tissue-factor-driven-coagulation-in-vitro-and-in-vivo
#3
Anna K Kopec, Alfred P Spada, Patricia C Contreras, Nigel Mackman, James P Luyendyk
Tissue factor (TF) is the primary activator of the blood coagulation cascade. Liver parenchymal cells (i.e., hepatocytes) express TF in a molecular state that lacks procoagulant activity. Hepatocyte apoptosis is an important feature of acute and chronic liver diseases, and Fas-induced apoptosis increases hepatocyte TF procoagulant activity in vitro. We determined the impact of a pan-caspase inhibitor, IDN-7314, on hepatocyte TF activity in vitro and TF-mediated coagulation in vivo. Treatment of primary mouse hepatocytes with the Fas death receptor ligand (Jo2, 0...
December 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29204688/pharmacokinetics-of-recombinant-asparaginase-in-children-with-acute-lymphoblastic-leukemia
#4
Swantje Völler, Uwe Pichlmeier, Anke Zens, Georg Hempel
PURPOSE: The objective of this study was to assess the pharmacokinetics of recombinant asparaginase (rASNase, Spectrila®) in children with acute lymphoblastic leukemia using a population pharmacokinetic approach in order to explore potential dosing recommendations. METHODS: Data on serum asparaginase activities of 124 children from three clinical studies were included in the analysis, covering an age range from 3 days to 17 years. Most patients received 5000 U/m2 rASNase intravenously every 3 days...
December 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29197605/sustained-thromboresistant-bioactivity-with-reduced-intimal-hyperplasia-of-heparin-bonded-ptfe-propaten-graft-in-a-chronic-canine-femoral-artery-bypass-model
#5
John Freeman, Aaron Chen, Roy J Weinberg, Tamuru Okada, Changyi Chen, Peter H Lin
INTRODUCTION: Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda Bioactive Surface Technology (CBAS) in a canine model. METHODS: Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult greyhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side while a control non-heparin graft was placed on the contralateral side...
November 29, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29185171/effect-of-xylan-sulfates-on-coagulation-of-human-blood-plasma
#6
N N Drozd, S A Kuznetsova, V A Levdansky, M A Mikhailenko
Sulfated derivatives of xylan (isolated from Bétula pubéscens wood) with average molecular weight ~34 kDa, sulfur content of 11.3-17.5%, a degree of substitution of 0.74-1.64 are anticoagulants of direct type of action. Antithrombin and antifactor Xa activities in three tested xylan samples did not differ and reached 30.8-31.8 and 13.5-14.3 U/mg, respectively.
November 28, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29173042/antithrombin-conformational-modulation-by-d-myo-inositol-3-4-5-6-tetrakisphosphate-tmi-a-novel-scaffold-for-the-development-of-antithrombotic-agents
#7
Pablo Ricardo Arantes, Horacio Pérez-Sánchez, Hugo Verli
Antithrombin (AT) is a serpin that inhibits mainly thrombin and fXa after being activated by binding to glycosaminoglycans as heparin and heparan sulfate. Upon binding, the native AT conformation, relatively inactive as a protease inhibitor, is converted to an activated form. Recently a new compound, named TMI, was discovered in our group with nanomolar affinity to antithrombin, and shown to be able to induce a partial activation of antithrombin. As TMI represents an original scaffold for structural optimizations aiming the development of new antithrombotic drugs, the present work demonstrated, through a series of molecular dynamics simulations, that TMI is able to modulate AT reactive center loop flexibility similarly to what is observed to heparin, as well as exposing AT P1 residue, Arg393...
November 26, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29148253/quantification-of-vascular-damage-in-acute-kidney-injury-with-fluorine-magnetic-resonance-imaging-and-spectroscopy
#8
Jeremy K Moore, Junjie Chen, Hua Pan, Joseph P Gaut, Sanjay Jain, Samuel A Wickline
PURPOSE: To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. METHODS: A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone)...
November 16, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29135476/thrombogenicity-evaluation-in-221-patients-with-haemophilia-b-treated-with-nonacog-alfa
#9
Pablo Rendo, Janice Lamb, Lynne Smith, Joanne Fuiman, Joan M Korth-Bradley
: Risk for thrombotic events with factor IX replacement therapy in patients with haemophilia B remains a concern for patients, those who treat them, and regulatory agencies, based on experience with early use of prothrombin complex concentrates. The current post hoc analysis assessed the incidence of thrombotic events and changes in prothrombin fragment 1 + 2, thrombin-antithrombin complex, and D-dimer in 221 patients with haemophilia B who received nonacog alfa in clinical studies. Thrombotic event and coagulation marker data were collected from 8 interventional studies utilizing on-demand, prophylactic, and preventive regimens in patients with haemophilia B...
November 10, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29112333/associations-of-activated-coagulation-factor-vii-and-factor-viia-antithrombin-levels-with-genome-wide-polymorphisms-and-cardiovascular-disease-risk
#10
N C Olson, L M Raffield, L A Lange, E M Lange, W T Longstreth, G Chauhan, S Debette, S Seshadri, A P Reiner, R P Tracy
ESSENTIALS: Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. SUMMARY: Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa)...
November 7, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29093435/recurrent-thrombosis-a-case-of-hereditary-thromboembolism
#11
Maria Concetta Giofrè, Francesca Napoli, Daniela La Rosa, Alessia Caruso, Natascia Laganà, Lucia Orlando Settembrini, Antonino Saitta, Antonio Giovanni Versace
BACKGROUND Thrombophilia is a predisposition to thrombosis. Genetic causes include antithrombin III, protein C, protein S, factor V Leiden, prothrombin 20210A allele, and MTHFR mutations. Other genetic factors causing thrombosis and pulmonary embolism have been identified in recent studies, including 4G/4G polymorphism of the PAI-1 gene. CASE REPORT A patient with a personal and family history of recurrent thrombosis and pulmonary embolism was admitted to our Internal Medicine Department. After the most common acquired risk factors for thromboembolism were ruled out, the patient and her family members underwent genetic diagnostic testing...
November 2, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29074563/pregnancy-thrombophilia-and-the-risk-of-a-first-venous-thrombosis-systematic-review-and-bayesian-meta-analysis
#12
REVIEW
F Nanne Croles, Kazem Nasserinejad, Johannes J Duvekot, Marieke Jha Kruip, Karina Meijer, Frank Wg Leebeek
Objective To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy.Design Systematic review and bayesian meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016.Review methods Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion...
October 26, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29042831/the-impact-of-antithrombin-iii-use-in-achieving-anticoagulant-goals-in-pediatric-patients
#13
Allison J Jones, Keliana L O'Mara, Brian J Kelly, Ravi S Samraj
OBJECTIVES: To determine the percentage of patients with >10% reduction in heparin infusion rate within 48 hours of antithrombin III (ATIII) administration. Secondary objectives include the achievement of therapeutic anticoagulation and determining the days of subtherapeutic infusion prior to supplementation. METHODS: Retrospective chart review of 12 patients younger than 18 years of age who received ATIII concentrate supplementation while on continuous heparin infusion...
September 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29035656/clinical-laboratory-and-hemostatic-findings-in-cats-with-naturally-occurring-sepsis
#14
Sigal Klainbart, Limor Agi, Tali Bdolah-Abram, Efrat Kelmer, Itamar Aroch
OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge)...
November 1, 2017: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/29031112/quantitative-analysis-of-antithrombin-iii-binding-site-in-low-molecular-weight-heparins-by-exhausetive-heparinases-digestion-and-capillary-electrophoresis
#15
Mingyu Zhang, Gong Li, Yi Zhang, Jingwu Kang
The antithrombin III (ATIII)-binding site, which contains a special 3-O-sulfated, N-sulfated glucosamine residue with or without 6-O-sulfation, is mainly responsible for the anticoagulant activity of heparin. Undergoing the chemical depolymerization process, the preservation of the ATIII-binding site in low molecular weight heparins (LMWHs) are varied leading to the fluctuation of the anticoagulant activity. Herein we report a capillary electrophoresis (CE) method in combination with heparinase digestion and affinity chromatography for the measurement of molar percentage of ATIII-binding site of LMWHs...
October 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29023362/glycocalyx-shedding-is-enhanced-by-age-and-correlates-with-increased-fluid-requirement-in-patients-with-major-burns
#16
Akinori Osuka, Hirofumi Kusuki, Kazuhiro Yoneda, Hiroshi Matsuura, Hisatake Matsumoto, Hiroshi Ogura, Masashi Ueyama
BACKGROUND: Massive fluid shift following severe burn injury leads to edema and intravascular fluid loss that may result in burn-induced compartment syndrome (BICS) when corrected by aggressive fluid resuscitation. Factors causing this fluid shift remain unclear. Because glycocalyx regulates endothelial permeability, we hypothesized that glycocalyx shedding would increase fluid requirements in burn patients. This prospective cohort study aimed to identify relationships between shedding of the glycocalyx and fluid requirements following burn injury...
October 11, 2017: Shock
https://www.readbyqxmd.com/read/28981954/differential-effect-of-the-ultra-low-dose-and-standard-estrogen-plus-dydrogesterone-therapy-on-thrombin-generation-and-fibrinolysis-in-postmenopausal-women
#17
Magdalena Piróg, Robert Jach, Olga Kacalska-Janssen
INTRODUCTION: The objective of this study was to estimate the effects of different doses of oral hormone therapy (HT) on thrombin generation and fibrinolytic activity in postmenopausal women after 12 months of treatment. MATERIAL AND METHODS: Thrombin generation, fibrinolysis activators and inhibitors were determined before and after 12 months of treatment. Participants (180) were assigned (1:1:1) as follows: (1) standard HT group, 17β-estradiol (1 mg/day) with dydrogesterone (5 mg/day); (2) ultra-low dose HT group, 17β-estradiol (0...
October 5, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28978851/future-prospects-of-hemostatic-treatment-for-hemophilia-patients
#18
Keiji Nogami
In the treatment of hemophilia patients, factor (F) VIII or FIX product prophylaxis results in arthropathy prevention and quality of life (QOL) improvement. Serious issues concerning hemostatic treatment of hemophilia include frequent intravenous administration of products, inhibitor development, and hemostatic treatment of patients with inhibitors. To overcome these challenges, products with extended half-life were developed. Furthermore, alternative products based on new concepts of hemostatic therapy were developed...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28972371/enzymatic-generation-of-highly-anticoagulant-bovine-intestinal-heparin
#19
Li Fu, Kevin Li, Daisuke Mori, Makoto Hirakane, Lei Lin, Navdeep Grover, Payel Datta, Yanlei Yu, Jing Zhao, Fuming Zhang, Murat Yalcin, Shaker A Mousa, Jonathan S Dordick, Robert J Linhardt
Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.
October 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28943821/continuous-antithrombin-iii-administration-in-pediatric-veno-arterial-extracorporeal-membrane-oxygenation
#20
Kristina M Nelson, Lizbeth A Hansen, Marie E Steiner, Gwenyth A Fischer, John Dehnel, Sameer Gupta
The purpose of this retrospective case-control study is to determine the effect of continuous antithrombin III (ATIII) infusion on extracorporeal membrane oxygenation (ECMO) coagulation. All ECMO patients within the pediatric intensive care unit from January 2012 to July 2014 were included. Comparison was made between those who received continuous infusion ATIII through a standardized replacement protocol with historic controls receiving intermittent ATIII doses. Patients receiving the continuous infusion ATIII protocol spent more time in goal ACT range (71...
July 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
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