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Clotting factors

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https://www.readbyqxmd.com/read/28530135/prolonged-expression-of-secreted-enzymes-in-dogs-after-liver-directed-delivery-of-i-sleeping-beauty-i-transposons-implications-for-non-viral-gene-therapy-of-systemic-disease
#1
Elena L Aronovich, Kendra Anne Hyland, Bryan C Hall, Jason B Bell, Erik R Olson, Myra Urness Rusten, David W Hunter, N Matthew Ellinwood, R Scott McIvor, Perry B Hackett
The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice including hemophilias A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis (MPS) types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. We recently reported modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), we demonstrated transgenic protein in the plasma for up to six weeks post-infusion...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28529414/comparison-of-efficacy-of-autologous-platelet-rich-fibrin-versus-saline-dressing-in-chronic-venous-leg-ulcers-a-randomised-controlled-trial
#2
Anirudh Somani, Reena Rai
BACKGROUND: Venous leg ulcer is a chronic condition, and various treatment modalities are available. Platelet-rich fibrin (PRF) is one of the newer modalities and it contains fibroblast growth factor (GF), vascular endothelial GF, angiopoitin and platelet-derived GF which enhances the wound healing. Hence, we conducted a randomised controlled trial to compare the efficacy of PRF versus saline dressing in chronic venous leg ulcers. AIM: This study aims to compare the efficacy of autologous PRF with saline dressing in patients with chronic venous leg ulcer and to compare the mean reduction in ulcer area at the end of 4 weeks...
January 2017: Journal of Cutaneous and Aesthetic Surgery
https://www.readbyqxmd.com/read/28526142/anticoagulant-reversal-and-anesthetic-considerations
#3
REVIEW
Joseph Meltzer, Joseph R Guenzer
Bleeding complications are a common concern with the use of anticoagulant agents. In many situations, reversing of neutralizing their effects may be warranted. Prothrombin complex concentrate replaces coagulation factors lowered by warfarin, as does fresh frozen plasma, but in a more concentrated form. Protamine negates the effect of heparin and combines chemically with heparin molecules to form an inactive salt. It also partially reverses the effects of low-molecular-weight heparin. Recombinant activated factor VII is a nonspecific procoagulant that activates the extrinsic clotting pathway, resulting in thrombin generation, but does not directly neutralize the activity of any of the new oral anticoagulants...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28522812/selection-and-characterization-of-a-dna-aptamer-inhibiting-coagulation-factor-xia
#4
David A Donkor, Varsha Bhakta, Louise J Eltringham-Smith, Alan R Stafford, Jeffrey I Weitz, William P Sheffield
Factor XIa (FXIa) is a serine protease that catalyzes the activation of Factor IX (FIX) in the blood coagulation cascade. FXIa and its precursor FXI are emergent therapeutic targets for the development of safer anticoagulant agents. Here, we sought a novel DNA-based agent to inhibit FXIa. Towards this goal, an 80 base, single-stranded DNA aptamer library (containing a 40 base randomized core) was screened for FXIa-binding candidates, using ten rounds of positive and negative selection. After selection, 6 of 89 different sequences inhibited FXIa-mediated chromogenic substrate S2366 cleavage...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516512/defective-%C3%AE-2-antiplasmin-cross-linking-and-thrombus-stability-in-a-case-of-acquired-factor-xiii-deficiency
#5
Joanne L Mitchell, Sonja Wright, Sajida Kazi, Henry G Watson, Nicola J Mutch
Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition that is often misdiagnosed or missed completely. A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. Low activated FXIII (FXIIIa) activity levels and abnormal urea clot stability led to diagnosis of acquired FXIII deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose of FXIII concentrate and immunosuppression with prednisolone induced remission...
May 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28516358/mechanistic-modeling-of-the-pharmacodynamic-and-pharmacokinetic-relationship-of-tissue-factor-pathway-inhibitor-neutralizing-antibody-bay-1093884-in-cynomolgus-monkeys
#6
Jian-Ming Gu, Xiao-Yan Zhao, Thomas Schwarz, Joachim Schuhmacher, Andreas Baumann, Elena Ho, Babu Subramanyan, Kathy Tran, Timothy Myles, Chandra Patel, Maria Koellnberger
BAY 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (TFPI) in development as prophylaxis in patients with hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human, mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic (PD) biomarker after administration of BAY 1093884 to normal monkeys. In monkey plasma, BAY 1093884 exhibited an IC50 (concentration that inhibits 50%) of 4.65 and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively...
May 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#7
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28513800/sociodemographic-factors-and-functional-capacity-of-elderly-affected-by-stroke
#8
Michelinne Oliveira Machado Dutra, Alexsandro Silva Coura, Inacia Sátiro Xavier de França, Bertha Cruz Enders, Mayara Araújo Rocha
Introduction: Diseases of old age have shown increasing prevalence in society. One of them is stroke, which can be conceptualized as the interruption of cerebral blood supply due to a leakage or blood vessel obstruction caused by clots. Objective: To verify the associations between sociodemographic factors and the functional capacity of elderly affected by stroke. Methods: This is an epidemiological, cross-sectional, and quantitative study, including 118 elderly people with paralyses due to stroke, who were registered in one of the Family Health Strategies units of Campina Grande, Paraíba, Brazil...
January 2017: Revista Brasileira de Epidemiologia, Brazilian Journal of Epidemiology
https://www.readbyqxmd.com/read/28512053/effect-of-chitosan-and-coagulation-factors-on-the-wound-repair-phenotype-of-bioengineered-blood-clots
#9
Caroline D Hoemann, Catherine Marchand, Georges-Etienne Rivard, Hani El-Gabalawy, Patrice E Poubelle
Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B4 (LTB4) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB4 or inflammatory factors...
May 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28510738/pharmacokinetic-pharmacodynamic-model-for-unfractionated-heparin-dosing-during-cardiopulmonary-bypass
#10
X Delavenne, E Ollier, S Chollet, F Sandri, J Lanoiselée, S Hodin, A Montmartin, J-F Fuzellier, P Mismetti, L Gergelé
Background: High-dose heparin is used during cardiopulmonary bypass (CPB) to prevent thrombosis in the circuits used for extracorporeal circulation. The aim of this study was, initially, to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to assess the variability of PK/PD parameters and their correlation with the results of the routine haemostatic test activated clotting time (ACT) and thereafter to develop a Bayesian estimator enabling an individualized dosing strategy...
May 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28505011/in-vitro-assessment-of-the-effect-of-dabigatran-on-thrombosis-of-adult-and-neonatal-plasma-comparisons-using-thromboelastography-and-microscopic-visualization-of-fibrin-clot-structure
#11
Fadi F Nossair, Howard H W Chan, Jorell Gantioqui, Helen M Atkinson, Leslie R Berry, Anthony K C Chan
: Thromboelastography (TEG) is a global assay used for evaluating features of clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin that has not been studied in neonates using a sophisticated global assay, such as TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and qualitative characteristics. Our aim was to compare the TEG clotting profile of neonatal and adult platelet-poor plasma when exposed to different concentrations of dabigatran. We used commercially collected adult pooled plasma and neonatal cord blood collected from placentas of healthy full term newborns...
May 12, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28503124/factor-xiii-deficiency-and-thrombocytopenia-are-frequent-modulators-of-postoperative-clot-firmness-in-a-surgical-intensive-care-unit
#12
Sarah von Rappard, Corina Hinnen, Roger Lussmann, Manuela Rechsteiner, Wolfgang Korte
OBJECTIVE: Fibrinogen and factor XIII (FXIII) have been shown to critically influence clot firmness in the intraoperative setting and thus likely influence intraoperative bleeding. We were interested to identify potential modulators of postoperative clot firmness in a tertiary care hospital surgical intensive care unit setting, independent of their clinical course during surgery. METHODS: 272 day-shift consecutive patients were evaluated for whole blood clot firmness evaluated by the ROTEM® EXTEM thrombelastometric assay and various potential modulators of clot firmness upon arrival at the surgical intensive care unit (SICU)...
April 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28503122/thrombosis-in-inherited-fibrinogen-disorders
#13
REVIEW
Wolfgang Korte, Man-Chiu Poon, Alfonso Iorio, Michael Makris
Although inherited fibrinogen disorders (IFD) are primarily considered to be bleeding disorders, they are associated with a higher thrombotic complication risk than defects in other clotting factors. Managing IFD patients with thrombosis is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk which can be life-threatening. Due to the low prevalence of IFD, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. We searched the literature for cases of thrombosis among IFD patients and identified a total of 128 patient reports...
April 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28501622/the-role-of-plasmin-in-the-pathogenesis-of-murine-multiple-myeloma
#14
Salita Eiamboonsert, Yousef Salama, Hiroshi Watarai, Douaa Dhahri, Yuko Tsuda, Yoshio Okada, Koichi Hattori, Beate Heissig
Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is implicated in tumorigenesis. Although abnormalities of coagulation and fibrinolysis have been reported in multiple myeloma patients, the biological roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have not been elucidated. In this study, we established a murine model of fulminant MM with bone marrow and extramedullar engraftment after intravenous injection of B53 cells. We found that the fibrinolytic factor expression pattern in murine B53 MM cells is similar to the expression pattern reported in primary human MM cells...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28499509/ten-year-study-of-postoperative-complications-following-dental-extractions-in-patients-with-inherited-bleeding-disorders
#15
J-T Hsieh, K Klein, M Batstone
Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012...
May 9, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28497841/effect-of-fluid-resuscitation-with-balanced-solutions-on-platelets-in-vitro-simulation-of-20-volume-substitution
#16
Łukasz J Krzych, Piotr F Czempik
BACKGROUND: Fluid resuscitation in massive bleeding may cause coagulation disorders by dilution of platelets and clotting factors or by the definite influence on theirfunction. The aim of this study was to investigate the effects of balanced crystalloid and colloid solutions on platelets (PLT) in vitro using complex assessment of coagulation. METHODS: The study group was comprised of 32 American Society of Anesthesiologists physical status class I male volunteers, aged 21-35 (29 ± 4) years, weighting 59-103 (81...
May 12, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28490161/endovascular-stroke-therapy-focused-on-stent-retriever-thrombectomy-and-direct-clot-aspiration-historical-review-and-modern-application
#17
REVIEW
Dong-Hun Kang, Jaechan Park
Intravenous recombinant tissue plasminogen activator had been the only approved treatment for acute ischemic stroke since its approval in 1995. However, the restrictive time window, numerous contraindications, and its low recanalization rate were all limitations of this modality. Under those circumstances, endovascular stroke therapy went through a great evolution during the past two decades of intravenous thrombolysis. The results of the 2013 randomized trials for endovascular stroke therapy were neutral, although they were limited by insufficient imaging screening at enrollment, early-generation devices with less efficacy, and treatment delays...
May 2017: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/28488754/virtual-endovascular-treatment-of-intracranial-aneurysms-models-and-uncertainty
#18
REVIEW
Ali Sarrami-Foroushani, Toni Lassila, Alejandro F Frangi
Virtual endovascular treatment models (VETMs) have been developed with the view to aid interventional neuroradiologists and neurosurgeons to pre-operatively analyze the comparative efficacy and safety of endovascular treatments for intracranial aneurysms. Based on the current state of VETMs in aneurysm rupture risk stratification and in patient-specific prediction of treatment outcomes, we argue there is a need to go beyond personalized biomechanical flow modeling assuming deterministic parameters and error-free measurements...
May 10, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28486277/evaluation-of-recombinant-factor-viii-fc-eloctate-activity-by-thromboelastometry-in-a-multicenter-phase-3-clinical-trial-and-correlation-with-bleeding-phenotype
#19
Frank Driessler, Maricel G Miguelino, Glenn F Pierce, Robert T Peters, Jurg M Sommer
: The aim of this study was to compare the hemostatic efficacy of recombinant factor VIII Fc (rFVIIIFc) (Eloctate) and Advate by ex-vivo rotation thromboelastometry (ROTEM) of whole blood and to explore potential ROTEM parameters that may be more predictive of a patient's bleeding tendency than plasma FVIII activity. Thirteen clinical sites were selected to perform ROTEM on freshly collected blood samples from 44 patients in the phase 3 study for rFVIIIFc, including 16 patients undergoing sequential pharmacokinetic assessment of Advate and rFVIIIFc...
May 8, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28482571/optimization-and-development-of-maghemite-%C3%AE-fe2o3-filled-poly-l-lactic-acid-plla-thermoplastic-polyurethane-tpu-electrospun-nanofibers-using-taguchi-orthogonal-array-for-tissue-engineering-heart-valve
#20
Ehsan Fallahiarezoudar, Mohaddeseh Ahmadipourroudposht, Ani Idris, Noordin Mohd Yusof
Tissue engineering (TE) is an advanced principle to develop a neotissue that can resemble the original tissue characteristics with the capacity to grow, to repair and to remodel in vivo. This research proposed the optimization and development of nanofiber based scaffold using the new mixture of maghemite (γ-Fe2O3) filled poly-l-lactic acid (PLLA)/thermoplastic polyurethane (TPU) for tissue engineering heart valve (TEHV). The chemical, structural, biological and mechanical properties of nanofiber based scaffold were characterized in terms of morphology, porosity, biocompatibility and mechanical behaviour...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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