Overview of the Coagulation System
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Genetic and Epigenetic Determinants of Thrombin Generation Potential : an Epidemiological Approach Maria-Ares Rocanin-Arjo
Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach Maria-Ares Rocanin-Arjo To cite this version: Maria-Ares Rocanin-Arjo. Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach. Génétique humaine. Université Paris Sud - Paris XI, 2014. Français. NNT : 2014PA11T067. tel-01231859 HAL Id: tel-01231859 https://tel.archives-ouvertes.fr/tel-01231859 Submitted on 21 Nov 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ PARIS-SUD ÉCOLE DOCTORALE 420 : SANTÉ PUBLIQUE PARIS SUD 11, PARIS DESCARTES Laboratoire : Equip 1 de Unité INSERM UMR_S1166 Genomics & Pathophysiology of Cardiovascular Diseases THÈSE DE DOCTORAT SANTÉ PUBLIQUE - GÉNÉTIQUE STATISTIQUE par Ares ROCAÑIN ARJO Genetic and Epigenetic Determinants of Thrombin Generation Potential: an epidemiological approach. Date de soutenance : 20/11/2014 Composition du jury : Directeur de thèse : David Alexandre TREGOUET DR, INSERM U1166, Université Paris 6, Jussieu Rapporteurs : Guy MEYER PU_PH, Service de pneumologie. Hôpital européen Georges Pompidou Richard REDON DR, Institut thorax, UMR 1087 / CNRS UMR 6291 , Université de Nantes Examinateurs : Laurent ABEL DR, INSERM U980, Institut Imagine Marie Aline CHARLES DR, INSERM U1018, CESP Al meu pare (to my father /à mon père) Your genetics load the gun. -
Haemostatic Effects of Recombinant Coagulation Factor Viia
Haemostatic effects of recombinant coagulation factor VIIa Ton Lisman Lay-out: Pre Press, Baarn Cover illustration by Janine Marie¨n Inside illustrations by Geert Donker ISBN: 90-393-3192-8 Haemostatic effects of recombinant coagulation factor VIIa Bloedstelping door recombinant stollingsfactor VIIa (Met een samenvatting in het Nederlands) PROEFSCHIFT Ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de Rector Magnificus, Prof. Dr. W.H. Gispen, in gevolge het besluit van het College voor Promoties in het openbaar te verdedigen op dinsdag 17 december 2002 des ochtends te 10.30 uur. door Johannes Antonius Lisman Geboren op 10 Maart 1976, te Arnhem Promotor: Prof. Dr. Ph.G. de Groot Faculteit geneeskunde, Universiteit Utrecht Co-Promotor: Dr. H.K. Nieuwenhuis Faculteit geneeskunde, Universiteit Utrecht The studies described in this thesis were supported in part by an unrestricted educational grant from Novo Nordisk. Financial support by Novo Nordisk for the publication of this thesis is gratefully acknowledged. I’ve got a pen in my pocket does that make me a writer Standing on the mountain doesn’t make me no higher Putting on gloves don’t make you a fighter And all the study in the world Doesn’t make it science Paul Weller Contents Chapter 1. General Introduction 9 Haemophilia Chapter 2. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe haemophilia A 41 Appendix to chapter 2. Enhanced procoagulant and antifibrinolytic potential of superactive variants of recombinant factor VIIa in plasma from patients with severe haemophilia A 55 Cirrhosis and liver transplantation Chapter 3. -
A Novel Detection Method of Cleaved Plasma High-Molecular-Weight Kininogen Reveals Its Correlation with Alzheimer’S Pathology and Cognitive Impairment
Alzheimer’s& Dementia: Diagnosis, Assessment & Disease Monitoring 10 (2018) 480-489 Blood-Based Biomarkers A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer’s pathology and cognitive impairment Hitomi Yamamoto-Imotoa,b, Daria Zamolodchikova, Zu-Lin Chena, S. Lloyd Bournec, Syeda Rizvic, Pradeep Singha, Erin H. Norrisa, Frances Weis-Garciac, Sidney Stricklanda,* aPatricia and John Rosenwald Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA bResearch fellow of Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan cAntibody and Bioresource Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA Abstract Introduction: Accumulation of b-amyloid is a pathological hallmark of Alzheimer’s disease (AD). b-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi cleavage is observed in plasma of AD patients and mouse models by Western blot. For potential diagnostic purposes, a more quantitative method that can measure HKc levels in plasma with high sensitivity and specificity is needed. Methods: HKi/c, HKi, and HKc monoclonal antibodies were screened from hybridomas using direct ELISA with a fluorescent substrate. Results: We generated monoclonal antibodies recognizing HKi or HKc specifically and developed sand- wich ELISAs that can quantitatively detect HKi and HKc levels in human. These new assays show that decreased HKi and increased HKc levels in AD plasma correlate with dementia and neuritic plaque scores. Discussion: High levels of plasma HKc could be used as an innovative biomarker for AD. -
High Molecular Weight Kininogen Contributes to Early Mortality and Kidney Dysfunction in a Mouse Model of Sickle Cell Disease
DR ERICA SPARKENBAUGH (Orcid ID : 0000-0002-5529-7847) DR NIGEL KEY (Orcid ID : 0000-0002-8930-4304) Article type : Original Article High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease. Erica M Sparkenbaugh1, Malgorzata Kasztan2, Michael W Henderson1, Patrick Ellsworth1, Parker Ross Davis2, Kathryn J Wilson1, Brandi Reeves1, Nigel S Key1,5, Sidney Strickland3, Keith McCrae4, David M. Pollock2, Rafal Pawlinski1* 1UNC Blood Research Center, Division of Hematology & Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; 3Patricia and John Rosenwald Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY; 4Taussig Cancer Institute, Department of Hematology Oncology, Cleveland Clinic, Cleveland, OH; and 5Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. *Address for correspondence Rafal Pawlinski 8008B Mary Ellen Jones Bldg, CB 7035 This article has been accepted for publication and undergone full peer review but has not been throughAccepted Article the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/JTH.14972 This article is protected by copyright. All rights reserved 116 Manning Drive Chapel Hill, NC 27599-7025 Ph: 919-843-8387 Fax: 919-843-4896 Email: [email protected] Word Counts Abstract: 179 Main Text: 3691 Figures: Main manuscript has 6 figures, 2 tables; supplement has 4 tables and 3 figures. -
T-Kininogen 1/2 (F-12): Sc-103886
SANTA CRUZ BIOTECHNOLOGY, INC. T-kininogen 1/2 (F-12): sc-103886 The Power to Question BACKGROUND SOURCE In rats, four types of kininogens are produced, two of which are classical T-kininogen 1/2 (F-12) is an affinity purified goat polyclonal antibody raised high and low molecular weight kininogens and two of which are low molec- against a peptide mapping within an internal region of T-kininogen 2 of rat ular weight-like kininogens, designated T-kininogen 1 and T-kininogen 2. origin. T-kininogen 1 and T-kininogen 2 are 430 amino acid secreted rat proteins that each contain three cystatin domains and have nearly identical functions. PRODUCT Existing in plasma, both T-kininogen 1 and T-kininogen 2 are glycoproteins Each vial contains 200 µg IgG in 1.0 ml of PBS with < 0.1% sodium azide that act as thiol protease inhibitors and also play a role in blood coagulation, and 0.1% gelatin. specifically by helping to optimally position blood coagulation factors. Additionally, T-kininogen 1 and T-kininogen 2 act as precursors of the active Blocking peptide available for competition studies, sc-103886 P, (100 µg peptide Bradykinin and, as such, effect vascular permeability, hypotension peptide in 0.5 ml PBS containing < 0.1% sodium azide and 0.2% BSA). and smooth muscle contraction. APPLICATIONS REFERENCES T-kininogen 1/2 (F-12) is recommended for detection of full length and heavy 1. Furuto-Kato, S., Matsumoto, A., Kitamura, N. and Nakanishi, S. 1985. chain of T-kininogen 1 and 2 of rat origin by Western Blotting (starting dilu- Primary structures of the mRNAs encoding the rat precursors for tion 1:200, dilution range 1:100-1:1000), immunofluorescence (starting dilu- bradykinin and T-kinin. -
UK National Haemophilia Database Bleeding Disorder
UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 Published by United Kingdom Haemophilia Centre Doctors’ Organisation 2016 © UKHCDO 2016 Copyright of the United Kingdom Haemophilia Centre Doctors’ Organisation. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any other form by any means, electronic, mechanical, photocopying or otherwise without the prior permission in writing of the Chairman, c/o Secretariat, UKHCDO, City View House, Union Street, Ardwick, Manchester, M12 4JD. ISBN: 978-1-901787-20-7 UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 Contents 1. Chairman’s Report 1 2. Bleeding Disorder Statistics for 2015 / 2016 Contents 4 2.0. Comments on the Bleeding Disorder Statistics for 2015 / 2016 7 2.1 Haemophilia A 10 2.2 Haemophilia B 39 2.3 Von Willebrand Disease 56 2.4 Inhibitors Congenital and Acquired 61 2.5 Rarer Bleeding Disorders 67 2.6 Adverse Events 71 2.7 Morbidity and Mortality 74 3. Data Management Working Party 81 4. Haemtrack Group Report 84 5. Genetics Working Party 86 6. Genetic Laboratory Network 87 7. Inhibitor Working Party 89 8. Musculoskeletal Working Party 91 9. Paediatric Working Party 92 10. von Willebrand Disease Working Party 94 11. Obstetric Task Force 95 12. Therapeutic Task Force on Enhanced Half-Life Products 96 13. UK Haemophilia Data Managers’ Forum Group 97 14. Haemophilia Nurses’ Association 98 15. Haemophilia Chartered Physiotherapists’ Association 99 16. BCSH Haemostasis and Thrombosis Task Force 100 17. Haemophilia Society 102 18. The Macfarlane Trust 110 UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 1. -
Acquired Bleeding Disorders Tiede, Andreas; Zieger, Barbara; Lisman, Ton
University of Groningen Acquired bleeding disorders Tiede, Andreas; Zieger, Barbara; Lisman, Ton Published in: Haemophilia DOI: 10.1111/hae.14033 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2021 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Tiede, A., Zieger, B., & Lisman, T. (2021). Acquired bleeding disorders. Haemophilia, 27(S3), 5-13. https://doi.org/10.1111/hae.14033 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 30-09-2021 Received: 24 February 2020 | Accepted: 23 April 2020 DOI: 10.1111/hae.14033 SUPPLEMENT ARTICLE Acquired bleeding disorders Andreas Tiede1 | Barbara Zieger2 | Ton Lisman3 1Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Abstract Medical School, Hannover, Germany Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, 2 Division of Pediatric Hematology and cardiovascular or liver diseases, but can sometimes also arise spontaneously. -
Activation of the Plasma Kallikrein-Kinin System in Respiratory Distress Syndrome
003 I-3998/92/3204-043 l$03.00/0 PEDIATRIC RESEARCH Vol. 32. No. 4. 1992 Copyright O 1992 International Pediatric Research Foundation. Inc. Printed in U.S.A. Activation of the Plasma Kallikrein-Kinin System in Respiratory Distress Syndrome OLA D. SAUGSTAD, LAILA BUP, HARALD T. JOHANSEN, OLAV RPISE, AND ANSGAR 0. AASEN Department of Pediatrics and Pediatric Research [O.D.S.].Institute for Surgical Research. University of Oslo [L.B.. A.O.A.], Rikshospitalet, N-0027 Oslo 1, Department of Surgery [O.R.],Oslo City Hospital Ullev~il University Hospital, N-0407 Oslo 4. Department of Pharmacology [H. T.J.],Institute of Pharmacy, University of Oslo. N-0316 Oslo 3, Norway ABSTRAm. Components of the plasma kallikrein-kinin proteins that interact in a complicated way. When activated, the and fibrinolytic systems together with antithrombin 111 contact factors plasma prekallikrein, FXII, and factor XI are were measured the first days postpartum in 13 premature converted to serine proteases that are capable of activating the babies with severe respiratory distress syndrome (RDS). complement, fibrinolytic, coagulation, and kallikrein-kinin sys- Seven of the patients received a single dose of porcine tems (7-9). Inhibitors regulate and control the activation of the surfactant (Curosurf) as rescue treatment. Nine premature cascades. C1-inhibitor is the most important inhibitor of the babies without lung disease or any other complicating contact system (10). It exerts its regulatory role by inhibiting disease served as controls. There were no differences in activated FXII, FXII fragment, and plasma kallikrein (10). In prekallikrein values between surfactant treated and non- addition, az-macroglobulin and a,-protease inhibitor inhibit treated RDS babies during the first 4 d postpartum. -
High Molecular Weight Kininogen Is an Inhibitor of Platelet Calpain
High molecular weight kininogen is an inhibitor of platelet calpain. A H Schmaier, … , D Schutsky, R W Colman J Clin Invest. 1986;77(5):1565-1573. https://doi.org/10.1172/JCI112472. Research Article Recent studies from our laboratory indicate that a high concentration of platelet-derived calcium-activated cysteine protease (calpain) can cleave high molecular weight kininogen (HMWK). On immunodiffusion and immunoblot, antiserum directed to the heavy chain of HMWK showed immunochemical identity with alpha-cysteine protease inhibitor--a major plasma inhibitor of tissue calpains. Studies were then initiated to determine whether purified or plasma HMWK was also an inhibitor of platelet calpain. Purified alpha-cysteine protease inhibitor, alpha-2-macroglobulin, as well as purified heavy chain of HMWK or HMWK itself inhibited purified platelet calpain. Kinetic analysis revealed that HMWK inhibited platelet calpain noncompetitively (Ki approximately equal to 5 nM). Incubation of platelet calpain with HMWK, alpha-2- macroglobulin, purified heavy chain of HMWK, or purified alpha-cysteine protease inhibitor under similar conditions resulted in an IC50 of 36, 500, 700, and 1,700 nM, respectively. The contribution of these proteins in plasma towards the inhibition of platelet calpain was investigated next. Normal plasma contained a protein that conferred a five to sixfold greater IC50 of purified platelet calpain than plasma deficient in either HMWK or total kininogen. Reconstitution of total kininogen deficient plasma with purified HMWK to normal levels (0.67 microM) completely corrected the subnormal inhibitory activity. However, reconstitution of HMWK deficient plasma to normal levels of low molecular weight kininogen (2.4 microM) did not fully correct the subnormal calpain inhibitory capacity […] Find the latest version: https://jci.me/112472/pdf High Molecular Weight Kininogen Is an Inhibitor of Platelet Calpain Alvin H. -
Haemostasis & Thrombosis Laboratory User Guide
Haemostasis and Thrombosis Laboratory User Guide HAEMOSTASIS & THROMBOSIS LABORATORY USER GUIDE Document number: HPA-FO-002 WARNING: This is a controlled Page: 1 of 38 Author: Sarah Clarke document Date issued: 08/06/2020 Approved by: Head BMS Revision: 13.0 Haemostasis and Thrombosis Laboratory User Guide CONTENTS 1 INTRODUCTION ....................................................................................................... 4 2 LOCATION ................................................................................................................ 4 3 OPENING HOURS .................................................................................................... 5 3.1 Routine Coagulation Screening Service ................................................................ 5 3.2 Specialist Coagulation Service: ............................................................................. 5 4 CONTACT NUMBERS AND KEY PERSONNEL ...................................................... 6 5 CONFIDENTIALITY AND THE PROTECTION OF PERSONAL INFORMATION ..... 6 6 COMPLAINTS AND COMPLIMENTS……………………………………………………..7 7 CLINICAL INFORMATION ........................................................................................ 8 8 CLINICAL ADVICE AND INTERPRETATION ........................................................... 8 9 LABELLING OF REQUEST FORMS ........................................................................ 8 10 LABELLING OF SPECIMENS .................................................................................. 9 11 SAMPLE REQUIREMENTS -
Hemostasis: Definition
Bleeding disorders in children prof. Mariusz Wysocki, Katedra i Klinika Pediatrii, Hematologii i Onkologii Collegium Medicum Bydgoszcz UMK Toruń Hemostasis: definition • the sum total of those specialized functions within the circulating blood and its vessels that are intended to stop hemorrhage Hemostasis: players and phases • plasma factors • Vascular phase • inhibitors • Platelet phase • fibrinolisis • Plasma phase • platelets • vessels The coagulation system Bleeding disorders: clinical approach • history • physical examination • laboratory tests Bleeding diosrders: signs and symptoms Site Within normal May be abnormal Usually due to a limits and due to a bleeding disorder number of causes Nose Finger – induced Unilateral Recurrent, requiring medical intervention or causing anemia Oral Blood on brush Gum ooze < 30 min Gum ooze > 30 min Gut Rectal fissure, blood Haematemesis, in nappy Melaena Bleeding diorders: signs and symptoms Site Within normal May be abnormal Usually due to a limits and due to a bleeding disorder number of causes Menstrual loss 4 – 7 days „same as Mum” Loss leading to anemia or transfusion Skin Shins don’t count Bony prominences Spontaneous bruising over soft areas, laceration bleeding > 30 min Joints and muscles Trauma induced Spontaneous Intracranial Neonatal , trauma Spontaneous induced History: neonates (Sharathkumar A, 2008, Bowman M, 2009) • prolonged bleeding at the circumcision site, • cephalohematomas, • prolonged umbilical stump bleeding Warning signgs and symptoms: Epistaxis: (Sharathkumar A, 2008, -
The Role of the Plasminogen Activation System in Angioedema: Novel Insights on the Pathogenesis
Journal of Clinical Medicine Review The Role of the Plasminogen Activation System in Angioedema: Novel Insights on the Pathogenesis Filomena Napolitano and Nunzia Montuori * Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80135 Naples, Italy; fi[email protected] * Correspondence: [email protected]; Tel.: +39-0817463309 Abstract: The main physiological functions of plasmin, the active form of its proenzyme plasminogen, are blood clot fibrinolysis and restoration of normal blood flow. The plasminogen activation (PA) system includes urokinase-type plasminogen activator (uPA), tissue-type PA (tPA), and two types of plasminogen activator inhibitors (PAI-1 and PAI-2). In addition to the regulation of fibrinolysis, the PA system plays an important role in other biological processes, which include degradation of extracellular matrix such as embryogenesis, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation, and immune response. Recently, the link between PA system and angioedema has been a subject of scientific debate. Angioedema is defined as localized and self- limiting edema of subcutaneous and submucosal tissues, mediated by bradykinin and mast cell mediators. Different forms of angioedema are linked to uncontrolled activation of coagulation and fibrinolysis systems. Moreover, plasmin itself can induce a potentiation of bradykinin production with consequent swelling episodes. The number of studies investigating the PA system involvement in angioedema has grown in recent years, highlighting its relevance in etiopathogenesis. In this review, we present the components and diverse functions of the PA system in physiology and its importance in angioedema pathogenesis. Citation: Napolitano, F.; Montuori, Keywords: angioedema; fibrinolysis; plasmin; uPAR; tPA N.