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"Contact pathway"

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https://www.readbyqxmd.com/read/29760205/abnormal-plasma-clot-formation-and-fibrinolysis-reveal-bleeding-tendency-in-patients-with-partial-factor-xi-deficiency
#1
Gillian N Gidley, Lori A Holle, John Burthem, Paula H B Bolton-Maggs, Feng-Chang Lin, Alisa S Wolberg
Individuals with factor XI (FXI) deficiency have a variable bleeding risk that cannot be predicted from plasma FXI antigen or activity. This limitation can result in under- or overtreatment of patients and risk of bleeding or thrombosis. Previously, plasma clot fibrinolysis assays showed sensitivity to bleeding tendency in a small cohort of patients with severe FXI deficiency. Here, we determined the ability of plasma clot formation, structure, and fibrinolysis assays to predict bleeding tendency in a larger, independent cohort of patients with severe and partial FXI deficiency...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29746819/continuous-thrombin-generation-in-whole-blood-new-applications-for-assessing-activators-and-inhibitors-of-coagulation
#2
Shannon M Prior, Kenneth G Mann, Kalev Freeman, Saulius Butenas
Hemostatic tests have been utilized to clarify the blood coagulation potential. The novel thrombin generation (TG) assay of this study provides explicit information and is the most physiologically-relevant hemostatic test ex vivo. We describe how this assay allows for TG under a number of relevant circumstances. First, whole blood (WB) from healthy individuals was analyzed ± 5 pM tissue factor (TF) and ± contact pathway inhibition. Without an exogenous initiator TG was decreased and delayed, but addition of 5 pM TF shortened the lag phase and increased peak thrombin...
May 7, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29727892/hemostasis-during-extreme-exertion
#3
Cécile Hélène Kicken, Adam Miszta, Hilde Kelchtermans, Bas De Laat
Exercise is protective against cardiovascular disease, but can also provoke sudden cardiac death, a phenomenon referred to as "the exercise paradox." Extreme exertion is known to induce a rebalanced hemostatic state by causing hypercoagulability and concomitantly enhanced fibrinolysis. Over the past decade, novel techniques for quantifying hemostasis have been introduced, which may provide new insights into this process. This review summarizes recent literature on the effect of extreme exertion of both short and long duration on coagulation, fibrinolysis, and recovery of hemostatic balance...
May 4, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29700007/abnormal-clotting-of-the-intrinsic-contact-pathway-in-alzheimer-disease-patients-is-related-to-cognitive-ability
#4
Georgette L Suidan, Pradeep K Singh, Sunita Patel-Hett, Zu-Lin Chen, Dmitri Volfson, Hitomi Yamamoto-Imoto, Erin H Norris, Robert D Bell, Sidney Strickland
Alzheimer disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) deposition. Although peripheral inflammation and cerebrovascular pathology are reported in AD, there is a lack of plasma biomarkers in this field. Because the contact system is triggered in patient plasma, we hypothesized that the hemostasis profile could be a novel biomarker in AD. Here, we assessed the clotting profile in plasma from AD patients and age-matched controls. Utilizing clinically relevant assays, thromboelastography and activated partial thromboplastin time, we found impaired clot initiation and formation rate in AD patient plasma...
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29619369/cell-receptor-and-cofactor-interactions-of-the-contact-activation-system-and-factor-xi
#5
REVIEW
Monika Pathak, Bubacarr Gibril Kaira, Alexandre Slater, Jonas Emsley
The contact activation system (CAS) or contact pathway is central to the crosstalk between coagulation and inflammation and contributes to diverse disorders affecting the cardiovascular system. CAS initiation contributes to thrombosis but is not required for hemostasis and can trigger plasma coagulation via the intrinsic pathway [through factor XI (FXI)] and inflammation via bradykinin release. Activation of factor XII (FXII) is the principal starting point for the cascade of proteolytic cleavages involving FXI, prekallikrein (PK), and cofactor high molecular weight kininogen (HK) but the precise location and cell receptor interactions controlling these reactions remains unclear...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29563660/ethnic-diversity-inter-group-attitudes-and-countervailing-pathways-of-positive-and-negative-inter-group-contact-an-analysis-across-workplaces-and-neighbourhoods
#6
James Laurence, Katharina Schmid, Miles Hewstone
This study advances the current literature investigating the relationship between contextual out-group exposure, inter-group attitudes and the role of inter-group contact. Firstly, it introduces the concept of contact-valence into this relationship; that is, whether contact is experienced positively or negatively. Secondly, it presents a comparative analysis of how processes of out-group exposure and frequency of (valenced) contact affect prejudice across both neighbourhoods and workplaces. Applying path analysis modelling to a nationally-representative sample of white British individuals in England, we demonstrate, across both contexts, that increasing out-group exposure is associated with higher rates of both positively- and negatively-valenced contact...
2018: Social Indicators Research
https://www.readbyqxmd.com/read/29392546/potential-health-risk-assessment-through-ingestion-and-dermal-contact-arsenic-contaminated-groundwater-in-jianghan-plain-china
#7
Ran Li, Yi-Ming Kuo, Wen-Wen Liu, Cheng-Shin Jang, Enmin Zhao, Liquan Yao
Groundwater contamination with high arsenic (As) levels has caused serious health problem in Jianghan Plain. This study presents a framework to evaluate the results and their probable influencing factors of non-carcinogenic risk and carcinogenic risk in Shahu Village. An appropriate health risk assessment for residents exposing to As through ingestion and dermal contact pathways is also discussed in the paper. Hazard quotient (HQ) and target cancer risk (TR) are adopted to compute the non-carcinogenic and carcinogenic effects for residents, respectively...
February 1, 2018: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/29378353/contact-system-activation-and-cancer-new-insights-in-the-pathophysiology-of-cancer-associated-thrombosis
#8
E Campello, M W Henderson, D F Noubouossie, P Simioni, N S Key
Cancer induces a systemic hypercoagulable state that elevates the baseline thrombotic risk of affected patients. This hypercoagulable state reflects a complex interplay between cancer cells and host cells and the coagulation system as part of the host response to cancer. Although the tissue factor (TF)/factor VIIa pathway is proposed to be the principal initiator of fibrin formation in cancer patients, clinical studies have not shown a consistent relationship between circulating TF levels (often measured as plasma microvesicle-associated TF) and the risk of thrombosis...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#9
REVIEW
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28950949/g-protein-coupled-kinin-receptors-and-immunity-against-pathogens
#10
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28912558/an-omniphobic-lubricant-infused-coating-produced-by-chemical-vapor-deposition-of-hydrophobic-organosilanes-attenuates-clotting-on-catheter-surfaces
#11
Maryam Badv, Iqbal H Jaffer, Jeffrey I Weitz, Tohid F Didar
Catheter associated thrombosis is an ongoing problem. Omniphobic coatings based on tethering biocompatible liquid lubricants on self-assembled monolayers of hydrophobic organosilanes attenuate clotting on surfaces. Herein we report an efficient, non-invasive and robust process for coating catheters with an antithrombotic, omniphobic lubricant-infused coating produced using chemical vapor deposition (CVD) of hydrophobic fluorine-based organosilanes. Compared with uncoated catheters, CVD coated catheters significantly attenuated thrombosis via the contact pathway of coagulation...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738274/discovery-and-assessment-of-water-soluble-coumarins-as-inhibitors-of-the-coagulation-contact-pathway
#12
Charlotte Bouckaert, Shu Zhu, José W P Govers-Riemslag, Maxime Depoorter, Scott L Diamond, Lionel Pochet
Over the last decade, the coagulation factor XIIa (FXIIa) has seen renewed interest as a therapeutic target. Indeed, its inhibition could offer a protection against thrombosis without increasing the risk of bleeding. Moreover, it could answer the need for a safe prevention of blood-contacting medical devices-related thrombosis. Among the FXII and FXIIa inhibitors already described in literature, organic small-molecular-weight inhibitors are rather left behind. In this study, we were focused on the discovery and assessment of water soluble small molecules...
July 19, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28576714/alginate-microbeads-are-coagulation-compatible-while-alginate-microcapsules-activate-coagulation-secondary-to-complement-or-directly-through-fxii
#13
Caroline Gravastrand, Shamal Hamad, Hilde Fure, Bjørg Steinkjer, Liv Ryan, Josè Oberholzer, John D Lambris, Igor Lacík, Tom Eirik Mollnes, Terje Espevik, Ole-Lars Brekke, Anne Mari Rokstad
Alginate microspheres are presently under evaluation for future cell-based therapy. Their ability to induce harmful host reactions needs to be identified for developing the most suitable devices and efficient prevention strategies. We used a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbeads (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules)...
August 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28338598/characterization-of-distinct-coagulopathic-phenotypes-in-injury-pathway-specific-drivers-and-implications-for-individualized-treatment
#14
S Ariane Christie, Lucy Z Kornblith, Benjamin M Howard, Amanda S Conroy, Ryan C Kunitake, Mary F Nelson, Carolyn M Hendrickson, Carolyn S Calfee, Rachael A Callcut, Mitchell Jay Cohen
BACKGROUND: International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation...
June 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28287584/a-microfluidic-flow-chamber-model-for-platelet-transfusion-and-hemostasis-measures-platelet-deposition-and-fibrin-formation-in-real-time
#15
Katrijn R Six, Rosalie Devloo, Britt Van Aelst, Philippe Vandekerckhove, Hendrik B Feys, Veerle Compernolle
Microfluidic models of hemostasis assess platelet function under conditions of hydrodynamic shear, but in the presence of anticoagulants, this analysis is restricted to platelet deposition only. The intricate relationship between Ca2+ -dependent coagulation and platelet function requires careful and controlled recalcification of blood prior to analysis. Our setup uses a Y-shaped mixing channel, which supplies concentrated Ca2+ /Mg2+ buffer to flowing blood just prior to perfusion, enabling rapid recalcification without sample stasis...
February 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286749/factors-xi-and-xii-as-targets-for-new-anticoagulants
#16
REVIEW
Jeffrey I Weitz, James C Fredenburgh
Compared with vitamin K antagonists, the direct oral anticoagulants (DOACs) are simpler to administer and are associated with less intracranial bleeding. Nonetheless, even with the DOACs, bleeding still occurs and many patients with atrial fibrillation fail to receive anticoagulant thromboprophylaxis because of the fear of bleeding. Therefore, there is an urgent need for safer anticoagulants. Recent investigations into the biochemistry of hemostasis and thrombosis have identified new targets for development of novel anticoagulants...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28095402/a-general-shear-dependent-model-for-thrombus-formation
#17
Alireza Yazdani, He Li, Jay D Humphrey, George Em Karniadakis
Modeling the transport, activation, and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions. We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro experimental data and can be used over a wide range of flow shear rates ([Formula: see text]). We introduce an Eulerian-Lagrangian model where hemodynamics is solved on a fixed Eulerian grid, while platelets are tracked using a Lagrangian framework...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28032527/bioreactivity-of-stent-material-activation-of-platelets-coagulation-leukocytes-and-endothelial-cell-dysfunction-in-vitro
#18
Veronique Ollivier, Caroline Roques, Nicolas Receveur, Matthias Gratz, Laurent Feldman, Didier Letourneur, Christian Gachet, Pierre H Mangin, Martine Jandrot-Perrus
Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants...
September 2017: Platelets
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#19
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27925683/inorganic-polyphosphate-a-key-modulator-of-inflammation
#20
REVIEW
S M Hassanian, A Avan, A Ardeshirylajimi
Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mammalian target of rapamycin complex-1 (mTORC1) and mTORC2 pathways, respectively. Through interaction with receptor for advanced glycation end products (RAGE) and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins...
February 2017: Journal of Thrombosis and Haemostasis: JTH
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