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Chi Zhang, Peizhe Zhang, Hongxia Li, Lianhua Han, Lei Zhang, Lei Zhang, Xiangjun Yang
OBJECTIVES: Dabigatran etexilate is widely used for stroke prevention in the patients with atrial fibrillation. The anticoagulation activity of dabigatran is not necessary monitored in routine clinical practice. We aimed to study the effect of dabigatran on thrombin generation (TG) and coagulation assays in rabbit and human plasma. METHODS: Rabbits received different concentrations of dabigatran etexilate (5 mg/kg, 10 mg/kg). Patients with atrial fibrillation took 110 mg dabigatran etexilate twice daily...
March 15, 2018: Thrombosis Research
Ihosvany Fernández Bello, Víctor Jiménez-Yuste, Raquel de Paz, Mónica Martín Salces, Raul Justo Sanz, Elena Monzón Manzano, Elena G Arias-Salgado, María Teresa Álvarez Román, María Isabel Rivas Pollmar, Isabel Goyanes, Nora V Butta
Etiopathogenesis of myelodysplastic syndrome (MDS) might cause per se an anomalous haemostasis that can be even more deteriorated by thrombocytopaenia. So, evaluation of haemostasis in patients with MDS rises as a necessity.This work aimed to characterize haemostasis in non-bleeder MDS patients with a platelet count similar to healthy controls to establish differences between the two groups not related to thrombocytopaenia.Thromboelastometry in samples from MDS patients suggested the existence of at least two antagonistic processes: one of them giving a hypocoagulable pattern (prolonged clotting time and lower α angle) and another conferring a procoagulant profile (decreased fibrinolysis)...
March 19, 2018: Thrombosis and Haemostasis
Kenneth E Remy, Mark H Yazer, Arun Saini, Ajlana Mehanovic-Varmaz, Sharon R Rogers, Col Andrew P Cap, Philip C Spinella
BACKGROUND: Agitation of platelet units stored at room temperature is performed routinely to maintain platelet function and leukoreduction of blood products is standard of care in many countries to reduce immune consequences of transfusion. The effect of agitation and leukoreduction on whole blood stored at 4° C requires investigation as reductions in hemostatic capacity of whole blood may reduce its efficacy in treating trauma-induced coagulopathy and platelet dysfunction. We hypothesize that agitation of whole blood will not affect hemostatic function and that leukoreduction will reduce hemostatic function of whole blood...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Cleo Desormeaux, Tereza Bautzova, Sonia Garcia-Caraballo, Corinne Rolland, Maria Raffaella Barbaro, Stuart M Brierley, Giovanni Barbara, Nathalie Vergnolle, Nicolas Cenac
Proteases and Protease-Activated Receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons, and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators.Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2 and PAR4 was assessed by immunohistochemistry and RT-qPCR in whole DRG or in primary cultures of isolated neurons...
March 15, 2018: Pain
Katrine Munk Begtrup, Johanne Andersen Hojbjerg, Birgitte Vrou Offersen, Anne-Mette Hvas
Cancer is associated with increased risk of venous thromboembolic disease. Venous thromboembolic disease accounts for a substantial addition to morbidity and mortality rates in cancer patients and is the second leading cause of death in cancer patients, exceeded only by the underlying cancer. Only few previous studies have investigated the influence of radiotherapy on hemostasis and whether radiotherapy in itself causes an increased risk of venous thromboembolic disease. The aim was to investigate if adjuvant radiotherapy affects hemostasis after surgery and chemotherapy in patients with breast cancer...
March 19, 2018: Platelets
Masanori Tsujimoto, Yukiko Enomoto, Masafumi Miyai, Yusuke Egashira, Toru Iwama
Purpose To determine the best platelet function test for in-stent tissue protrusion following carotid artery stenting (CAS). Methods Patients who underwent CAS were recruited prospectively in this observational study. Combination of aspirin 100 mg/day and clopidogrel 75 mg/day was administered for a minimum of 7 days prior to procedure. Platelet aggregation was measured by light transmittance aggregometry (LTA) following stimulation by adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide (TRAP) and by the point of care assay, VerifyNow which measures aspirin and thienopyridine reaction units...
January 1, 2018: Journal of International Medical Research
Ayako Uchinaka, Maho Yoshida, Kiyoka Tanaka, Yoshinosuke Hamada, Seiji Mori, Yoshitaka Maeno, Shigeru Miyagawa, Yoshiki Sawa, Kohzo Nagata, Hirofumi Yamamoto, Naomasa Kawaguchi
OBJECTIVE: Left ventricular (LV) remodeling alters the contractile and relaxation properties and induces myocardial stiffness. As LV remodeling progresses, the amount of collagen type III (Col3) is gradually decreased, being replaced by collagen type I (Col1). We evaluated whether Col3 overexpression improved cardiac function and remodeling in a rat with ischemic cardiomyopathy (ICM). We also investigated the functional motif and mechanism of thrombin-cleaved N-terminal osteopontin (N-OPN) on cardiac remodeling...
February 21, 2018: Journal of Thoracic and Cardiovascular Surgery
Vincent-Philippe Lavallée, Jalila Chagraoui, Tara MacRae, Miriam Marquis, Arnaud Bonnefoy, Jana Krosl, Sébastien Lemieux, Anne Marinier, Caroline Pabst, Georges-Étienne Rivard, Josée Hébert, Guy Sauvageau
Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor...
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hember Vicci, Antonio Eblen-Zajjur, Mercedes López, Gustavo Crespo, Maria Navarro
Low-molecular weight heparins (LMWH) are anticoagulants that have shown anti-inflammatory activity in several experimental models. Hot water burn inflammatory model accurately simulates human clinical situations allowing its use for nociception test and evaluation of anti-inflammatory drugs. The present study aims to evaluate the enoxaparin pretreatment on local and systemic inflammation biomarkers in the animal burn model. Inflammation was induced by submersing the rat left hind paw in water at 60o  C for 60 s...
March 16, 2018: Inflammopharmacology
Galia Spectre, Fariborz Mobarrez, Ragnhild Stålesen, Claes-Göran Östenson, David Varon, Håkan Wallen, Paul Hjemdahl
Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry...
March 16, 2018: Platelets
Lixiu Wang, Yayan Bi, Muxin Yu, Tao Li, Dongxia Tong, Xiaoyan Yang, Cong Zhang, Li Guo, Chunxu Wang, Yan Kou, Zengxiang Dong, Valerie A Novakovic, Ye Tian, Junjie Kou, Masood A Shammas, Jialan Shi
BACKGROUND: The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). METHODS: NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy...
May 1, 2018: International Journal of Cardiology
Y Dargaud, X Delavenne, D P Hart, S Meunier, P Mismetti
Over the past decades, haemophilia management has continually evolved, with prophylaxis now considered the treatment of choice. Prophylaxis primarily seeks to prevent bleeding and haemarthrosis episodes from occurring and avert the otherwise inevitable haemophilic arthropathy. Yet, numerous unanswered issues remain. These concern dose levels, dosing intervals, ways of integrating variability in bleeding phenotype, patient age, joint status, lifestyle, physical activity, treatment adherence and individual responses to FVIII or FIX concentrates...
March 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Sandra Schulz, Manfred Maitz, Stefanie Hänsel, Lars D Renner, Carsten Werner
Advanced blood contacting biomaterials are designed to combine antiseptic and anticoagulant functionalities. Here, we present a new in vitro methodology for the analysis of bacterial adhesion and growth after the preceding human whole blood incubation of the tested materials. Poly(styrene) surfaces as well as thrombin-responsive and non-responsive poly(ethylene glycol)-heparin hydrogel coatings, with and without silver functionalization, were analyzed with this approach using freshly drawn human whole blood and various human pathogens (Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli)...
March 15, 2018: Biomaterials Science
Yusuke Ito, Kengo Noguchi, Yoshiyuki Morishima, Kyoji Yamaguchi
: No rodent models are currently available for evaluating inhibitors of the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) without exogenous supplementation of tissue-type plasminogen activator (tPA). Characterization of tPA transgenic rats as a tool for the nonclinical evaluation of TAFIa inhibitors is the objective of the current study. tPA transgenic rats were subjected to rat models of tissue-factor-induced thromboembolism, FeCl3-induced deep vein thrombosis (DVT) and arterial thrombosis, and tail bleeding...
March 13, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Hui Y Lim, Cheryl Ng, Joseph Rigano, Mark Tacey, Geoffrey Donnan, Harshal Nandurkar, Prahlad Ho
: Myeloproliferative neoplasms (MPN) are independent risks for thrombotic events. Routine laboratory tests are inadequate to evaluate the underlying procoagulant state. Global coagulation assays such as thromboelastography, thrombin and fibrin generation may provide better assessment of coagulation activation and thereby of thrombosis risk. Participants with MPN were recruited. Thromboelastography was performed on citrated whole blood while thrombin generation using calibrated automated thrombogram, fibrin generation using overall haemostatic potential assays and P-selectin were quantified on platelet-poor plasma...
March 13, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Silvia Ravera, Maria Grazia Signorello, Martina Bartolucci, Sara Ferrando, Lucia Manni, Federico Caicci, Daniela Calzia, Isabella Panfoli, Alessandro Morelli, Giuliana Leoncini
BACKGROUND INFORMATION: Energy demand in human platelets is very high, to carry out their functions. As for most human cells, the aerobic metabolism represents the primary energy source in platelets, even though mitochondria are negligibly represented. Following the hypothesis that other structures could be involved in chemical energy production, in this work, we have investigated the functional expression of an extramitochondrial aerobic metabolism in platelets. RESULTS: Oximetric and luminometric analyses showed that platelets consume large amounts of oxygen and produce ATP in the presence of common respiring substrates, such as pyruvate + malate or succinate, although morphological electron microscopy analysis showed that these contain few mitochondria...
March 14, 2018: Biology of the Cell
A Bar-Ilan, T Livnat, M Hoffmann, L Binder, M Zakar, R Guy, Y Felikman, L Moschcovich, B Shenkman, D Monroe, O Hershkovitz, G Kenet, G Hart
INTRODUCTION: Recombinant FVIIa (rFVIIa) is an effective treatment for haemophilia through frequent administration. However, the short half-life of rFVIIa decreases its prophylactic ability to reduce bleeding. Carboxy-terminal peptide (CTP)-modified FVIIa (MOD-5014) is a long-acting rFVIIa developed for on-demand treatment of haemophilia using either an intravenous or subcutaneous injection with the aim of less frequent administrations, as well as for prophylactic use. AIM: The comprehensive evaluation of the activity MOD-5014 vs commercially available rhFVIIa, as well as their interaction with cofactors and inhibitors...
March 14, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Zdeňka Hajšmanová, Pavla Šigutová, Alena Lavičková
Idarucizumab is designed to reverse the anticoagulant effect of dabigatran. This case report describes the administration of three independent doses of idarucizumab to a 76-year-old man suffering from atrial flutter being treated with dabigatran to prevent ischaemic stroke. The last dose of dabigatran was administered in the morning of the same day the patient was transferred to hospital because of the need for urgent pericardium puncture. Baseline dTT (dilute thrombin time) reached 700 ng/mL as glomerular filtration (GF) dropped to 0...
February 2018: Hämostaseologie
Yan Sun, Xiao-Li Liu, Dai Zhang, Fang Liu, Yu-Jing Cheng, Yue Ma, Yu-Jie Zhou, Ying-Xin Zhao
BACKGROUND: Intraplaque angiogenesis, the process of generating new blood vessels mediated by endothelial cells, contributes to plaque growth, intraplaque hemorrhage, and thromboembolic events. Platelet-derived exosomes (PLT-EXOs) affect angiogenesis in multiple ways. The ability of miR-126, one of the best-characterized miRNAs that regulates angiogenesis, carried by PLT-EXOs to influence angiogenesis via the regulation of the proliferation and migration of endothelial cells is unknown...
March 13, 2018: Current Vascular Pharmacology
Sophie Testa, Oriana Paoletti, Cristina Legnani, Claudia Dellanoce, Emilia Antonucci, Benilde Cosmi, Vittorio Pengo, Daniela Poli, Rossella Morandini, Roberto Testa, Armando Tripodi, Gualtiero Palareti
BACKGROUND: Direct oral anticoagulants(DOACs) are administered at fixed dose without need for dose adjustment by lab testing. A high inter-individual variability in the drug blood levels was shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events,565 consecutivenaïve patients withatrial fibrillation (AF), were enrolled in this study performed within the START-Laboratory Registry. METHODS: DOAC specific measurements [diluted thrombin time (dTT) or anti-FIIa calibrated for dabigatran; anti-FXa calibrated for rivaroxaban or apixaban] at C-trough were performed locally at steady state within 15-25 days from starting treatment...
March 12, 2018: Journal of Thrombosis and Haemostasis: JTH
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