Fibrin Induces Release of Von Willebrand Factor from Endothelial Cells
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Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism
International Journal of Molecular Sciences Review Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism Michał Z ˛abczyk 1,2 , Joanna Natorska 1,2 and Anetta Undas 1,2,* 1 John Paul II Hospital, 31-202 Kraków, Poland; [email protected] (M.Z.); [email protected] (J.N.) 2 Institute of Cardiology, Jagiellonian University Medical College, 31-202 Kraków, Poland * Correspondence: [email protected]; Tel.: +48-12-614-30-04; Fax: +48-12-614-21-20 Abstract: Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. -
Urokinase, a Promising Candidate for Fibrinolytic Therapy for Intracerebral Hemorrhage
LABORATORY INVESTIGATION J Neurosurg 126:548–557, 2017 Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage *Qiang Tan, MD,1 Qianwei Chen, MD1 Yin Niu, MD,1 Zhou Feng, MD,1 Lin Li, MD,1 Yihao Tao, MD,1 Jun Tang, MD,1 Liming Yang, MD,1 Jing Guo, MD,2 Hua Feng, MD, PhD,1 Gang Zhu, MD, PhD,1 and Zhi Chen, MD, PhD1 1Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing; and 2Department of Neurosurgery, 211st Hospital of PLA, Harbin, People’s Republic of China OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fi- brinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor–κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. -
Update on Antithrombin I (Fibrin)
©2007 Schattauer GmbH,Stuttgart AnniversaryIssueContribution Update on antithrombinI(fibrin) Michael W. Mosesson 1957–2007) The Blood Research Institute,BloodCenter of Wisconsin, Milwaukee,Wisconsin, USA y( Summary AntithrombinI(fibrin) is an important inhibitor of thrombin exosite 2.Thelatterreaction results in allostericchanges that generation that functions by sequestering thrombin in the form- down-regulate thrombin catalytic activity. AntithrombinIdefi- Anniversar ingfibrin clot,and also by reducing the catalytic activity of fibrin- ciency (afibrinogenemia), defectivethrombin binding to fibrin th boundthrombin.Thrombin binding to fibrin takesplace at two (antithrombin Idefect) found in certain dysfibrinogenemias (e.g. 50 classesofnon-substrate sites: 1) in thefibrin Edomain (two per fibrinogen Naples 1), or areduced plasma γ ’ chain content (re- molecule) throughinteractionwith thrombin exosite 1; 2) at a ducedantithrombin Iactivity),predispose to intravascular singlesite on each γ ’ chain through interaction with thrombin thrombosis. Keywords Fibrinogen,fibrin, thrombin, antithrombin I ThrombHaemost 2007; 98: 105–108 Introduction meric with respecttoits γ chains,and accounts for ~85% of human plasma fibrinogen. Thrombinbinds to its substrate, fibrinogen, through an anion- Low-affinity thrombin binding activity reflects thrombin ex- binding sitecommonlyreferred to as ‘exosite 1’ (1,2). Howell osite1bindinginEdomain of fibrin, as recentlydetailedbyana- recognized nearly acenturyago that the fibrin clot itself exhibits lysesofthrombin-fibrin -
Functional Plasminogen Activator Inhibitor 1 Is Retained on The
ARTICLE Hemostasis Functional plasminogen activator inhibitor 1 is Ferrata Storti Foundation retained on the activated platelet membrane following platelet activation Gael B. Morrow,° Claire S. Whyte and Nicola J. Mutch Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK °Current address: Radcliffe Department of Medicine, University of Oxford, Oxford, UK Haematologica 2020 Volume 105(12):2824-2833 ABSTRACT latelets harbor the primary reservoir of circulating plasminogen acti- vator inhibitor 1 (PAI-1), but the reportedly low functional activity of Pthis pool of inhibitor has led to debate over its contribution to throm- bus stability. Here we analyze the fate of PAI-1 secreted from activated platelets and examine its role in maintaining thrombus integrity. Activation of platelets results in translocation of PAI-1 to the outer leaflet of the mem- brane, with maximal exposure in response to strong dual agonist stimula- tion. PAI-1 is found to co-localize in the 'cap' of phosphatidylserine-expos- ing platelets with its co-factor, vitronectin, and fibrinogen. Inclusion of tirofiban or Gly-Pro-Arg-Pro significantly attenuated exposure of PAI-1, indicating a crucial role for integrin αIIbb3 and fibrin in delivery of PAI-1 to the activated membrane. Separation of platelets post stimulation into sol- uble and cellular components revealed the presence of PAI-1 antigen and activity in both fractions, with approximately 40% of total platelet-derived PAI-1 remaining associated with the cellular fraction. Using a variety of fib- rinolytic models, we found that platelets produce a strong stabilizing effect against tissue plasminogen activator (tPA)-mediated clot lysis. Platelet lysate, as well as soluble and cellular fractions, stabilize thrombi against premature degradation in a PAI-1-dependent manner. -
The Plasmin–Antiplasmin System: Structural and Functional Aspects
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Bern Open Repository and Information System (BORIS) Cell. Mol. Life Sci. (2011) 68:785–801 DOI 10.1007/s00018-010-0566-5 Cellular and Molecular Life Sciences REVIEW The plasmin–antiplasmin system: structural and functional aspects Johann Schaller • Simon S. Gerber Received: 13 April 2010 / Revised: 3 September 2010 / Accepted: 12 October 2010 / Published online: 7 December 2010 Ó Springer Basel AG 2010 Abstract The plasmin–antiplasmin system plays a key Plasminogen activator inhibitors Á a2-Macroglobulin Á role in blood coagulation and fibrinolysis. Plasmin and Multidomain serine proteases a2-antiplasmin are primarily responsible for a controlled and regulated dissolution of the fibrin polymers into solu- Abbreviations ble fragments. However, besides plasmin(ogen) and A2PI a2-Antiplasmin, a2-Plasmin inhibitor a2-antiplasmin the system contains a series of specific CHO Carbohydrate activators and inhibitors. The main physiological activators EGF-like Epidermal growth factor-like of plasminogen are tissue-type plasminogen activator, FN1 Fibronectin type I which is mainly involved in the dissolution of the fibrin K Kringle polymers by plasmin, and urokinase-type plasminogen LBS Lysine binding site activator, which is primarily responsible for the generation LMW Low molecular weight of plasmin activity in the intercellular space. Both activa- a2M a2-Macroglobulin tors are multidomain serine proteases. Besides the main NTP N-terminal peptide of Pgn physiological inhibitor a2-antiplasmin, the plasmin–anti- PAI-1, -2 Plasminogen activator inhibitor 1, 2 plasmin system is also regulated by the general protease Pgn Plasminogen inhibitor a2-macroglobulin, a member of the protease Plm Plasmin inhibitor I39 family. -
RIASTAP®, Fibrinogen Concentrate (Human) Lyophilized Powder for Solution for Intravenous Injection
HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------------CONTRAINDICATIONS ------------------------------------ These highlights do not include all the information needed to use RIASTAP • Known anaphylactic or severe systemic reactions to human plasma-derived products (4). safely and effectively. See full prescribing information for RIASTAP. ---------------------------------WARNINGS AND PRECAUTIONS---------------------------- RIASTAP®, Fibrinogen Concentrate (Human) • Monitor patients for early signs of anaphylaxis or hypersensitivity reactions and if necessary, discontinue administration and institute appropriate treatment (5.1). Lyophilized Powder for Solution for Intravenous Injection • Thrombotic events have been reported in patients receiving RIASTAP. Weigh the benefits of administration versus the risks of thrombosis (5.2). Initial U.S. Approval: 2009 • Because RIASTAP is made from human blood, it may carry a risk of transmitting ------------------------------------RECENT MAJOR CHANGES--------------------------------- infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent Indications and Usage (1) 06/2021 and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent (5.3). Dosage and Administration (2.2) 07/2020 -------------------------------------ADVERSE REACTIONS-------------------------------------- ----------------------------------INDICATIONS AND USAGE----------------------------------- • The most serious adverse reactions observed are thrombotic episodes (pulmonary RIASTAP, Fibrinogen -
A Guide for People Living with Von Willebrand Disorder CONTENTS
A guide for people living with von Willebrand disorder CONTENTS What is von Willebrand disorder (VWD)?................................... 3 Symptoms............................................................................................... 5 Types of VWD...................................................................................... 6 How do you get VWD?...................................................................... 7 VWD and blood clotting.................................................................... 11 Diagnosis................................................................................................. 13 Treatment............................................................................................... 15 Taking care of yourself or your child.............................................. 19 (Education, information, first aid/medical emergencies, medication to avoid) Living well with VWD......................................................................... 26 (Sport, travel, school, telling others, work) Special issues for women and girls.................................................. 33 Connecting with others..................................................................... 36 Can I live a normal life with von Willebrand disorder?............. 37 More information................................................................................. 38 2 WHAT IS VON WILLEBRAND DISORDER (VWD)? Von Willebrand disorder (VWD) is an inherited bleeding disorder. People with VWD have a problem with a protein -
The Minimum Concentration of Fibrinogen Needed for Platelet Aggregation Using ADP
RESEARCH ○○○○○○○○ The Minimum Concentration of Fibrinogen Needed for Platelet Aggregation using ADP ROBERT F CORNELL, TIM R RANDOLPH ○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○ OBJECTIVE: Determine the minimum concentration of plasma INDEX TERMS: ADP; aggregation; fibrinogen; platelets. fibrinogen needed to stimulate the aggregation of platelets, col- lected from normal subjects, using ADP. Clin Lab Sci 2001;15(1):30 DESIGN: Platelet rich plasmas (300 x 109 platelets/L) were made Robert F Cornell II was a student in the Department of Clinical and adjusted to final fibrinogen concentrations of 75, 19, 5, and 0 Laboratory Science, Saint Louis University Health Sciences Center, St mg/dL using fibrinogen free serum. Each fibrinogen concentra- Louis MO when this research was done. Downloaded from tion in all twelve subjects was aggregated with ADP. Tim R Randolph MS is an Assistant Professor in the Department of SETTING: Research laboratory in the Department of Clinical Clinical Laboratory Science, School of Allied Health Professions, Saint Laboratory Science at Saint Louis University. Louis University Health Sciences Center, St Louis MO. PARTICIPANTS: Twelve healthy volunteers of both genders, be- Address for correspondence: Tim R Randolph MS, Saint Louis Uni- http://hwmaint.clsjournal.ascls.org/ tween the ages of 18 and 60 years who were not pregnant and versity School of Allied Health Professions, Department of Clinical Labo- weighed at least 110 pounds were included in the study. Subjects ratory Science, Room 3096, 3437 Caroline St, St Louis MO 63104. were excluded from the study if they had ingested aspirin within (314) 577-8518, (314) 577-8503 (fax). [email protected] one week prior to blood collection. -
Recommended Abbreviations for Von Willebrand Factor and Its Activities
RECOMMENDED ABBREVIATIONS FOR VON WILLEBRAND FACTOR AND ITS ACTIVITIES On behalf of the von Willebrand Factor Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis Claudine Mazurier and Francesco Rodeghiero Previous official recommendations concerning the abbreviations for von Willebrand Factor (and factor VIII) are 15 years old and were limited to "vWf" for the protein and "vWf:Ag" for the antigen (1). Nowadays, the various properties of von Willebrand Factor (ristocetin cofactor activity and capacity to bind to either collagen or factor VIII) are better defined and may warrant specific abbreviations. Furthermore, the protein synthesized by the von Willebrand factor gene is now abbreviated as pre-pro-VWF (2). Accordingly, the subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the ISTH has recommended new abbreviations for von Willebrand Factor antigen and its various activities, currently measured by immunologic or functional assays (Table I). It is hoped that a uniform application of the abbreviations recommended here will improve communication among scientists and clinicians, especially for those who are less familiar with the field. Table 1: Recommended abbreviations for von Willebrand Factor and its activities Attribute Recommended abbreviations Mature protein VWF Antigen VWF:Ag Ristocetin cofactor activity VWF:RCo Collagen binding capacity VWF:CB Factor VIII binding capacity VWF:FVIIIB REFERENCES: 1 – Marder VJ, Mannucci PM, Firkin BG, Hoyer LW and Meyer D. Standard nomenclature for factor VIII and von Willebrand factor: a recommendation by the International Committee on Thrombosis and Haemostasis. Thromb. Haemost. 1985, 54, 871-2. 2 – Goodeve AC, Eikenboom JCJ, Ginsburg D, Hilbert L, Mazurier C, Peake IR, Sadler JE, Rodeghiero F on behalf of the ISTH SSC subcommittee on von Willebrand Factor. -
Biomechanical Thrombosis: the Dark Side of Force and Dawn of Mechano- Medicine
Open access Review Stroke Vasc Neurol: first published as 10.1136/svn-2019-000302 on 15 December 2019. Downloaded from Biomechanical thrombosis: the dark side of force and dawn of mechano- medicine Yunfeng Chen ,1 Lining Arnold Ju 2 To cite: Chen Y, Ju LA. ABSTRACT P2Y12 receptor antagonists (clopidogrel, pras- Biomechanical thrombosis: the Arterial thrombosis is in part contributed by excessive ugrel, ticagrelor), inhibitors of thromboxane dark side of force and dawn platelet aggregation, which can lead to blood clotting and A2 (TxA2) generation (aspirin, triflusal) or of mechano- medicine. Stroke subsequent heart attack and stroke. Platelets are sensitive & Vascular Neurology 2019;0. protease- activated receptor 1 (PAR1) antag- to the haemodynamic environment. Rapid haemodynamcis 1 doi:10.1136/svn-2019-000302 onists (vorapaxar). Increasing the dose of and disturbed blood flow, which occur in vessels with these agents, especially aspirin and clopi- growing thrombi and atherosclerotic plaques or is caused YC and LAJ contributed equally. dogrel, has been employed to dampen the by medical device implantation and intervention, promotes Received 12 November 2019 platelet thrombotic functions. However, this platelet aggregation and thrombus formation. In such 4 Accepted 14 November 2019 situations, conventional antiplatelet drugs often have also increases the risk of excessive bleeding. suboptimal efficacy and a serious side effect of excessive It has long been recognized that arterial bleeding. Investigating the mechanisms of platelet thrombosis -
A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: to Target Or Not to Target?
International Journal of Molecular Sciences Review A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target? Machteld Sillen and Paul J. Declerck * Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B-3000 Leuven, Belgium; [email protected] * Correspondence: [email protected] Abstract: Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of plasminogen activators (PAs) and is therefore an important inhibitor of the plasminogen/plasmin system. Being the fast-acting inhibitor of tissue-type PA (tPA), PAI-1 primarily attenuates fibrinolysis. Through inhibition of urokinase-type PA (uPA) and interaction with biological ligands such as vitronectin and cell-surface receptors, the function of PAI-1 extends to pericellular proteolysis, tissue remodeling and other processes including cell migration. This review aims at providing a general overview of the properties of PAI-1 and the role it plays in many biological processes and touches upon the possible use of PAI-1 inhibitors as therapeutics. Keywords: plasminogen activator inhibitor-1; PAI-1; fibrinolysis; cardiovascular disease; cancer; inflammation; fibrosis; aging Citation: Sillen, M.; Declerck, P.J. 1. Introduction A Narrative Review on Plasminogen Plasminogen activator inhibitor-1 (PAI-1) belongs to the family of serine protease Activator Inhibitor-1 and Its inhibitors (serpins) and is an important regulator of the plasminogen/plasmin system (Patho)Physiological Role: To Target (Figure1)[ 1]. This system revolves around the conversion of the zymogen plasmino- or Not to Target?. Int. J. Mol. Sci. 2021, gen into the active enzyme plasmin through proteolytic cleavage that is mediated by 22, 2721. -
Protein C Product Monograph 1995 COAMATIC® Protein C Protein C
Protein C Product Monograph 1995 COAMATIC® Protein C Protein C Protein C, Product Monograph 1995 Frank Axelsson, Product Information Manager Copyright © 1995 Chromogenix AB. Version 1.1 Taljegårdsgatan 3, S-431 53 Mölndal, Sweden. Tel: +46 31 706 20 00, Fax: +46 31 86 46 26, E-mail: [email protected], Internet: www.chromogenix.se COAMATIC® Protein C Protein C Contents Page Preface 2 Introduction 4 Determination of protein C activity with 4 snake venom and S-2366 Biochemistry 6 Protein C biochemistry 6 Clinical Aspects 10 Protein C deficiency 10 Assay Methods 13 Protein C assays 13 Laboratory aspects 16 Products 17 Diagnostic kits from Chromogenix 17 General assay procedure 18 COAMATIC® Protein C 19 References 20 Glossary 23 3 Protein C, version 1.1 Preface The blood coagulation system is carefully controlled in vivo by several anticoagulant mechanisms, which ensure that clot propagation does not lead to occlusion of the vasculature. The protein C pathway is one of these anticoagulant systems. During the last few years it has been found that inherited defects of the protein C system are underlying risk factors in a majority of cases with familial thrombophilia. The factor V gene mutation recently identified in conjunction with APC resistance is such a defect which, in combination with protein C deficiency, increases the thrombosis risk considerably. The Chromogenix Monographs [Protein C and APC-resistance] give a didactic and illustrated picture of the protein C environment by presenting a general view of medical as well as technical matters. They serve as an excellent introduction and survey to everyone who wishes to learn quickly about this field of medicine.