648 research outputs found

    Newly-Recognized Roles of Factor XIII in Thrombosis

    Get PDF
    Arterial and venous thrombosis are major contributors to coagulation-associated morbidity and mortality. Greater understanding of mechanisms leading to thrombus formation and stability is expected to lead to improved treatment strategies. Factor XIII (FXIII) is a transglutaminase found in plasma and platelets. During thrombosis, activated FXIII crosslinks fibrin and promotes thrombus stability. Recent studies have provided new information about FXIII activity during coagulation and its effects on clot composition and function. These findings reveal newly-recognized roles for FXIII in thrombosis. Herein, we review published literature on FXIII biology and effects on fibrin structure and stability, epidemiologic data associating FXIII with thrombosis, and evidence from animal models indicating FXIII has an essential role in determining thrombus stability, composition, and size

    New findings on venous thrombogenesis

    Get PDF
    Venous thrombosis (VT) is the third most common cause of cardiovascular death worldwide. Complications from VT and pulmonary embolism are the leading cause of lost disability-adjusted life years. Risks include genetic (e.g., non-O blood group, activated protein C resistance, hyperprothrombinemia) and acquired (e.g., age, surgery, cancer, pregnancy, immobilisation, female hormone use) factors. Pathophysiologic mechanisms that promote VT are incompletely understood, but involve abnormalities in blood coagulability, vessel function, and flow (so-called Virchow’s Triad). Epidemiologic studies of humans, animal models, and biochemical and biophysical investigations have revealed contributions from extrinsic, intrinsic, and common pathways of coagulation, endothelial cells, leukocytes, red blood cells, platelets, cell-derived microvesicles, stasis-induced changes in vascular cells, and blood rheology. Knowledge of these mechanisms may yield new therapeutic targets. Characterisation of mechanisms that mediate VT formation and stability, particularly in aging, are needed to advance understanding of VT

    Venous Thromboembolism: Risk Factors, Biomarkers, and Treatment

    Get PDF
    Articles in this series: •Zhu T, Martinez I, Emmerich J. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol. 2009;29:298–310. •Jang MJ, Choi W, Bang SM, Lee T, Yeo-Kyeoung K, Ageno W, Doyeun Oh. Metabolic syndrome is associated with venous thromboembolism in the Korean population. Arterioscler Thromb Vasc Biol. 2009;29:311–315. •Sousou T, Khorana AA. New insights into cancer-associated thrombosis. Arterioscler Thromb Vasc Biol. 2009;29:316–320. •Farmer-Boatwright MK, Roubey RAS. Venous thrombosis in the antiphospholipid syndrome. Arterioscler Thromb Vasc Biol. 2009;29:321–325. •James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol. 2009;29:326–331. •Pabinger I, Ay C. Biomarkers and venous thromboembolism. Arterioscler Thromb Vasc Biol. 2009;29:332–336. In 2005, the U.S. Senate declared March as deep vein thrombosis (DVT) awareness month. This is the second year in which we have highlighted this event with a collection of 6 articles in Arteriosclerosis, Thrombosis, and Vascular Biology focused on DVT. It is estimated that 2 million Americans per year develop DVT, which is associated with life-threatening pulmonary embolism (PE). DVT and PE are collectively termed venous thromboembolism (VTE). Despite the large number of cases, a survey conducted by the American Public Health Association in 2002 found that 74% of Americans were unaware of venous thrombosis.1 The risk of VTE increases with thrombophilias, age, pregnancy, and comorbidities, including cancer and antiphospholipid syndrome (APS). It has not yet been determined whether similar mechanisms lead to VTE in each of these disorders. The articles in this issue describe current research into disorders associated with increased VTE risk, including potential pathophysiologic mechanisms, treatment of these clinical situations, and a review on biomarkers for the detection and prevention of VTE.

    Influence of Cellular and Plasma Procoagulant Activity on the Fibrin Network

    Get PDF
    At the nexus of cellular and plasma procoagulant activities lies fibrin, which is necessary to provide a clot's structural support. Abnormalities in fibrin network formation or function can result in either bleeding or thrombotic complications. Understanding relationships between procoagulant activity and normal fibrin formation, as well as pathophysiologic mechanisms leading to abnormal fibrin deposition, is essential for the continued development of hemostatic and antithrombotic therapies

    A portable blood plasma clot micro-elastometry device based on resonant acoustic spectroscopy

    Get PDF
    Abnormal blood clot stiffness is an important indicator of coagulation disorders arising from a variety of cardiovascular diseases and drug treatments. Here, we present a portable instrument for elastometry of microliter volume blood samples based upon the principle of resonant acoustic spectroscopy, where a sample of well-defined dimensions exhibits a fundamental longitudinal resonance mode proportional to the square root of the Young’s modulus. In contrast to commercial thromboelastography, the resonant acoustic method offers improved repeatability and accuracy due to the high signal-to-noise ratio of the resonant vibration. We review the measurement principles and the design of a magnetically actuated microbead force transducer applying between 23 pN and 6.7 nN, providing a wide dynamic range of elastic moduli (3 Pa–27 kPa) appropriate for measurement of clot elastic modulus (CEM). An automated and portable device, the CEMport, is introduced and implemented using a 2 nm resolution displacement sensor with demonstrated accuracy and precision of 3% and 2%, respectively, of CEM in biogels. Importantly, the small strains (<0.13%) and low strain rates (<1/s) employed by the CEMport maintain a linear stress-to-strain relationship which provides a perturbative measurement of the Young’s modulus. Measurements of blood plasma CEM versus heparin concentration show that CEMport is sensitive to heparin levels below 0.050 U/ml, which suggests future applications in sensing heparin levels of post-surgical cardiopulmonary bypass patients. The portability, high accuracy, and high precision of this device enable new clinical and animal studies for associating CEM with blood coagulation disorders, potentially leading to improved diagnostics and therapeutic monitoring

    Thrombin generation, fibrin clot formation and hemostasis

    Get PDF
    Hemostatic clot formation entails thrombin-mediated cleavage of fibrinogen to fibrin. Previous in vitro studies have shown that the thrombin concentration present during clot formation dictates the ultimate fibrin structure. In most prior studies of fibrin structure, clotting was initiated by adding thrombin to a solution of fibrinogen; however, clot formation in vivo occurs in an environment in which the concentration of free thrombin changes over the reaction course. These changes depend on local cellular properties and available concentrations of pro- and anti-coagulants. Recent studies suggest that abnormal thrombin generation patterns produce abnormally structured clots associated with an increased risk of bleeding or thrombosis. Further studies of fibrin formation during in situ thrombin generation are needed to understand fibrin clot formation in vivo

    Tissue factor and factor VIIa – Hemostasis and beyond

    Get PDF
    Initiation of the coagulation cascade via exposure of active tissue factor (TF) to blood and formation of the factor VIIa/TF complex is essential for hemostasis and is an initial procoagulant signal in thrombosis. As of early 2012, over 20,000 articles listed on PubMed describe advances in the understanding of TF biology in the settings of hemostasis and thrombosis, as well as in signaling events in cancer, sickle cell anemia, hyperlipidemia, and a broad spectrum of inflammatory disorders. It is both inspiring and humbling, then, to consider not only what has been learned about TF regulation, but also the number of questions still remaining about its role in physiology. This supplement reviews both well-accepted and currently-controversial topics in coagulation and factor VIIa/TF biology, with particular foci on non-hemostatic roles of TF, innovative approaches for the treatment of hemophilia, and novel in vivo models of bleeding and thrombosis

    Kinetic model facilitates analysis of fibrin generation and its modulation by clotting factors: implications for hemostasis-enhancing therapies

    Get PDF
    We developed a computational model that accounts for essential kinetic features of thrombin generation, fibrin formation, and fibrinolysis in diverse in vitro systems. We applied it to characterize strategies to improve hemostasis

    Book Reviews

    Get PDF
    Book 1Book Title: Getting into Residency: A Guide for Medical StudentsBook Author: Kenneth V. IsersonPp. xviii + 431. 28,95.Tucson:GalenPress.1993.ISBN1−883620−10−4.Book2BookTitle:MolecularBiologyofDigestiveDiseaseBookAuthor: Ed.byPhilipQuirkePp.vii+116.£15.London:BMJ.1994.ISBN0−7279−0827−8.Book3BookTitle:Parkinson′sDiseaseBookAuthor: Ed.byMertonSandler.Pp.ix+65.£12/US28,95. Tucson: Galen Press. 1993. ISBN 1-883620-10-4.Book 2Book Title: Molecular Biology of Digestive DiseaseBook Author: Ed. by Philip QuirkePp. vii + 116. £15. London: BMJ. 1994. ISBN 0-7279-0827-8.Book 3Book Title: Parkinson's DiseaseBook Author:  Ed. by Merton Sandler.Pp. ix + 65. £12/US24. London: John Libbey, 1993. ISBN 0-86196-404-7.Book 4Book Title: Brain Work and Mental Activity: Quantitative Studies With Radioactive TracersBook Author: Ed. by N. A. Lassen, D. A. Ingvar, M. A. Raichle &amp; L. FribergPP. 446. Illustrated. Copenhagen: Munksgaard. 1991. ISBN 87-16-10698-9.Book 5Book Title: Guidelines for Quality Assurance Programmes for Blood Transfusion ServicesBook Author: WHOPp. IV + 50. (Available in English; French and Spanish in preparation). SFr.12/US$10,80 (in developing countries SFr.8,40). Geneva: WHO. 1993. ISBN 92-4-154448-1. Order No. 1150392.Book 6Book Title: ABC of AlcoholBook Author: Ed. by Alex PatonPp. ix + 32. illustrated. £10. London: BMJ. 1994. ISBN 0-7279-D812-X.Book 7Book Title: Atlas of Surgical Exposures ofthe Lower ExtremityBook Author: A. Masquelet, C. McCullough, R Tubiana, I. Fyfe, L. Klenerman, E. LetoumelPp. 414. Illustrated. London: Manin Dunitz. 1993. ISBN 1-85317-D03-8
    • …
    corecore