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thrombosis, hemostasis

Elizabeth A Middleton, Matthew T Rondina, Hansjorg Schwertz, Guy A Zimmerman
Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions, and are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, some of these newly-discovered activities of platelets appear to contribute to tissue injury based on clinical investigations and animal models of disease...
March 19, 2018: American Journal of Respiratory Cell and Molecular Biology
Frans Moll, Iris Baumgartner, Michael Jaff, Chuke Nwachuku, Marco Tangelder, Gary Ansel, George Adams, Thomas Zeller, John Rundback, Michael Grosso, Min Lin, Michele F Mercur, Erich Minar
PURPOSE: To report a randomized study that investigated the safety (risk of major bleeds) and potential efficacy of edoxaban, an oral anticoagulant that targets the major components of arterial thrombi, to prevent loss of patency following endovascular treatment (EVT). METHODS: Between February 2012 and June 2014, 203 patients who underwent femoropopliteal EVT were randomized to receive aspirin plus edoxaban or aspirin plus clopidogrel for 3 months in the Edoxaban in Peripheral Arterial Disease (ePAD) study ( ClinicalTrials...
April 2018: Journal of Endovascular Therapy
A V Belyaev, J L Dunster, J M Gibbins, M A Panteleev, V Volpert
Hemostasis is a complex physiological mechanism that functions to maintain vascular integrity under any conditions. Its primary components are blood platelets and a coagulation network that interact to form the hemostatic plug, a combination of cell aggregate and gelatinous fibrin clot that stops bleeding upon vascular injury. Disorders of hemostasis result in bleeding or thrombosis, and are the major immediate cause of mortality and morbidity in the world. Regulation of hemostasis and thrombosis is immensely complex, as it depends on blood cell adhesion and mechanics, hydrodynamics and mass transport of various species, huge signal transduction networks in platelets, as well as spatiotemporal regulation of the blood coagulation network...
March 5, 2018: Physics of Life Reviews
Tony G Walsh, Alastair W Poole
Our understanding of platelet function has traditionally focused on their roles in physiological hemostasis and pathological thrombosis, the latter being causative of vessel occlusion and subsequent ischemic damage to various tissues. In particular, numerous in vivo studies have implicated causative roles for platelets in the pathogenesis of ischemia-reperfusion (I/R) injury to the myocardium. However, platelets clearly have more complex pathophysiological roles particularly as a result of the heterogeneous nature of biologically active cargo secreted from their granules, or contained within released microparticles or exosomes...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Francesco Caso, Marco Tasso, Pasquale Ambrosino, Matteo Nicola, Dario Di Minno, Roberta Lupoli, Livio Criscuolo, Paolo Caso, Francesco Ursini, Antonio Del Puente, Raffaele Scarpa, Luisa Costa, Rosario Peluso
BACKGROUND: Psoriatic arthritis is a chronic inflammatory arthropathy that affects 14%-30% of patients with skin and/or nail psoriasis and leading to severe physical limitations and disability. It has been included in the group of spondyloarthropathy with which it shares clinical, radiologic, and serologic features in addition to familial and genetic relationship. Beyond skin and joint involvement, psoriatic arthritis is characterized by a high prevalence of extra-articular manifestation and comorbidities, such as autoimmune, infectious and neoplastic diseases...
March 13, 2018: Reviews on Recent Clinical Trials
Sanne L N Brouns, Johanna P van Geffen, Johan W M Heemskerk
In recent years, considerable progress has been made in understanding the mechanisms involved in platelet activation during hemostasis and thrombosis. Parallel-plate flow chambers and other microfluidic devices have markedly contributed to this insight. Conversely, such flow devices are now increasingly used to monitor the combined processes of platelet aggregation, thrombus formation, and coagulation in human blood. Currently, by combining microspotting and multi-color fluorescence microscopy, this technology offers the capability of high-throughput measurement of platelet activation processes, even in small blood samples...
March 14, 2018: Platelets
Jean Amiral, Maxime Laroche, Jerard Seghatchian
For many years, the importance of fibrinolysis has been recognized, first for its intravascular antithrombotic action, and more recently for its many extravascular activities, associated with matrix degradation and tissue remodeling. In the blood circulation system, fibrinolysis prevents thrombosis, and is associated with various biological and clinical situations: risk factors for cardio-vascular diseases in high risk clinical situations (type II diabetes, hypertension, triglycerides, high BMI, elevated glucose, etc...
February 20, 2018: Transfusion and Apheresis Science
Frédéric Adam, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-Claude Bordet, Jian-Dong Huang, Marijke Bryckaert, Alain Fischer, Delphine Borgel, Geneviève de Saint Basile, Olivier D Christophe, Gaël Ménasché
OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiaohong Ruby Xu, George M Yousef, Heyu Ni
Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis...
March 8, 2018: Blood
Diego Butera, Freda Passam, Lining Ju, Kristina M Cook, Heng Woon, Camilo Aponte-Santamaría, Elizabeth Gardiner, Amanda K Davis, Deirdre A Murphy, Agnieszka Bronowska, Brenda M Luken, Carsten Baldauf, Shaun Jackson, Robert Andrews, Frauke Gräter, Philip J Hogg
Force-dependent binding of platelet glycoprotein Ib (GPIb) receptors to plasma von Willebrand factor (VWF) plays a key role in hemostasis and thrombosis. Previous studies have suggested that VWF activation requires force-induced exposure of the GPIb binding site in the A1 domain that is autoinhibited by the neighboring A2 domain. However, the biochemical basis of this "mechanopresentation" remains elusive. From a combination of protein chemical, biophysical, and functional studies, we find that the autoinhibition is controlled by the redox state of an unusual disulfide bond near the carboxyl terminus of the A2 domain that links adjacent cysteine residues to form an eight-membered ring...
February 2018: Science Advances
Shaoyun Zhang, Qiang Huang, Bin Xu, Jun Ma, Guorui Cao, Fuxing Pei
Little has been published on blood management in total hip and knee arthroplasty (THA and TKA, respectively) patients focusing on both hematopoiesis and hemostasis. Our aim was to explore the effectiveness and safety of an optimized blood management program in THA and TKA patients in a large, single-center, retrospective study.We retrospectively reviewed consecutive primary unilateral THA and TKA patients' data at our institution through the National Health Database. They were divided into 3 groups according to an optimized blood management program: group A-combined use of intravenous and topical tranexamic acid (TXA); group B-use of recombinant human erythropoietin (rHuEPO) and iron supplements in addition to treatments in group A; group C-use of additional multiple boluses of TXA in addition to treatments in group B...
January 2018: Medicine (Baltimore)
Arturo Giordano, Stefano Messina, Gennaro Maresca, Giuseppe Biondi-Zoccai
Purpose: Brachial access is occasionally used for endovascular procedures when other more established or safer ones (eg, femoral or radial) are contraindicated. Although manual compression is the standard of care after brachial arteriotomy, suboptimal compression may lead to bleeding or thrombosis. Arteriotomy closure devices have thus been proposed as an alternative means to achieve hemostasis after brachial arteriotomy. Yet, there is a paucity of evidence and a limited spectrum of devices suitable for brachial arteriotomy closure...
2018: Clinical Medicine Insights. Cardiology
Evan Tsiklidis, Carrie Sims, Talid Sinno, Scott L Diamond
Trauma with hypovolemic shock is an extreme pathological state that challenges the body to maintain blood pressure and oxygenation in the face of hemorrhagic blood loss. In conjunction with surgical actions and transfusion therapy, survival requires the patient's blood to maintain hemostasis to stop bleeding. The physics of the problem are multiscale: (a) the systemic circulation sets the global blood pressure in response to blood loss and resuscitation therapy, (b) local tissue perfusion is altered by localized vasoregulatory mechanisms and bleeding, and (c) altered blood and vessel biology resulting from the trauma as well as local hemodynamics control the assembly of clotting components at the site of injury...
February 27, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Coen Maas, Thomas Renné
Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII-driven-contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate provides protection from thromboembolic diseases without interfering with hemostasis...
February 26, 2018: Blood
Brian R Branchford, Marisol Betensky, Neil A Goldenberg
Multiple observational studies have identified risk factors for venous thromboembolism (VTE) in hospitalized children, but very few interventional studies have assessed the safety and efficacy of thromboprophylaxis in this population. In recent years, however, evidence in pediatric VTE risk stratification has grown considerably. This has led to the conception of a pediatric subpopulation-specific risk-based paradigm for mechanical and pharmacological thromboprophylaxis in hospitalized children. More research is required to validate and further refine pediatric subpopulation-specific risk models and to subsequently investigate risk-stratified thromboprophylaxis strategies for hospitalized children...
February 17, 2018: Thrombosis Research
Huong Nguyen, Khon Huynh, Volker R Stoldt
Soluble plasma fibronectin (Fn) with its inactive compact structure requires unfolding to assemble into active fibrils, which play a role in hemostasis and thrombosis. Fn fibril assembly involves Fn binding to cell receptors, biomechanical coupling of Fn to the cytoskeleton by integrins, exposure of self-assembly sites via contractile cell forces, and elongation of fibrils by Fn polymerization. In this report, we investigated the effect of platelet integrins and actin cytoskeleton on conformational changes of Fn induced by shear...
February 19, 2018: Biochemical and Biophysical Research Communications
Jessica P E Davis, Patrick G Northup, Stephen H Caldwell, Nicolas M Intagliata
Long thought to be hypocoagulable, new evidence suggests cirrhosis patients have "rebalanced" coagulation in the setting of decreased synthesis of both pro- and anti-coagulant factors. Traditional testing like PT/INR reflects only the decreased synthesis of pro-coagulant factors and thus does not correspond to bleeding or clotting risk in this population. In this review, we discuss the use of viscoelastic testing (VET), an assay of global hemostasis in cirrhosis patients. We describe the technique and interpretation of commercially available VET and assess the application of VET in both transplant and non-transplant cirrhosis populations...
March 1, 2018: Annals of Hepatology
Edward F Plow, Yunmei Wang, Daniel I Simon
Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis...
February 21, 2018: Blood
Dorit Hanein, Niels Volkmann
Integrins are bidirectional transmembrane receptors that play central roles in hemostasis and arterial thrombosis. They have been subject to structural studies for many years, in particular using X-ray crystallography, nuclear magnetic resonance spectroscopy, and two-dimensional negative stain electron microscopy. Despite considerable progress, a full consensus on the molecular mechanism of integrin activation is still lacking. Three-dimensional reconstructions of full-length human platelet integrin αIIb β3 in lipid-bilayer nanodiscs obtained by electron cryo-microscopy and single-particle reconstruction have shed new light on the activation process...
2018: Sub-cellular Biochemistry
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