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Fibrinolysis

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https://www.readbyqxmd.com/read/28219843/the-impact-of-the-endothelial-protein-c-receptor-on-thrombin-generation-and-clot-lysis
#1
Laura Pepler, Chengliang Wu, Dhruva J Dwivedi, Cynthia Wu, Paul Y Kim, Patricia C Liaw
INTRODUCTION: When thrombin is bound to thrombomodulin (TM), it becomes a potent activator of protein C (PC) and thrombin-activable fibrinolysis inhibitor (TAFI). Activation of PC is enhanced when PC is bound to the endothelial protein C receptor (EPCR). Activated protein C (APC) inhibits thrombin generation while activated TAFI (TAFIa) attenuates fibrinolysis. To determine the impact of diminished EPCR function on thrombin generation and fibrinolysis we generated cells that expressed TM and a variant of EPCR (R96C) that does not bind PC...
February 3, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28219085/fibrinolysis-in-trauma-myth-reality-or-something-in-between
#2
Mark Walsh, Jacob Shreve, Scott Thomas, Ernest Moore, Hunter Moore, Daniel Hake, Tim Pohlman, Patrick Davis, Victoria Ploplis, Andres Piscoya, Julie Wegner, John Bryant, Anton Crepinsek, James Lantry, Forest Sheppard, Francis Castellino
The emphasis on fibrinolysis as an important contributor to trauma-induced coagulopathy (TIC) has led to a debate regarding the relative clinical significance of fibrinolysis in the setting of trauma. The debate has centered on two camps. The one camp defines fibrinolysis in trauma by standard coagulation tests as well as fibrin split products, D-dimers, and plasmin/antiplasmin levels. This camp favors a more liberal use of tranexamic acid and attributes more significance to hyperfibrinolysis in TIC. The other camp favors a definition of fibrinolysis based on the viscoelastic tests (VET), rotational thromboelastometry (ROTEM), and thromboelastography (TEG)...
February 20, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28219084/diagnosis-and-treatment-of-hyperfibrinolysis-in-trauma-a-european-perspective
#3
Lewis S Gall, Karim Brohi, Ross A Davenport
Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. The mechanistic drivers and dynamics of fibrinolytic activation in response to injury and trauma resuscitation are currently unclear. Furthermore, therapeutic triggers are compounded by the lack of a sensitive and rapid diagnostic tool, with discrepancy between hyperfibrinolysis diagnosed by viscoelastic hemostatic assays versus biomarkers for fibrinolysis...
February 20, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28215474/establishment-of-disseminated-intravascular-coagulation-dic-model-by-a-single-iv-administration-of-escherichia-coli-derived-lipopolysaccharide-lps-to-cynomolgus-monkeys-and-evaluation-of-its-pathophysiological-status
#4
Hirofumi Minomo, Kengo Inoue, Shuko Sakaki, Takanobu Okazaki, Kinji Kobayashi, Kazuhiko Inoue, Atsuro Miyata
We prepared a DIC model by administrating LPS to cynomolgus monkeys, and investigated its potential for evaluations of new medicines for DIC therapy. Peripheral blood mononuclear cells (PBMC) collected from cynomolgus monkeys were incubated with LPS (8 types), and TNF-α levels in the media were measured. LPS from Escherichia coli (K-235) was most appropriate in terms of larger increases and smaller variation in TNF-α levels. PBMC from rats, cynomolgus monkeys or humans were incubated with LPS (K-235), and the TNF-α response to LPS was investigated...
February 2, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28215042/platelet-mediated-modulation-of-fibrinolysis
#5
Claire S Whyte, Joanne L Mitchell, Nicola J Mutch
Platelets are crucial to the hemostatic response. Their role in coagulation is well documented and they have been considered for some time to promote resistance of thrombi to fibrinolysis. Platelets confer resistance to lysis by promoting clot retraction of the immediate fibrin network and through release of plasminogen activator inhibitor-1 from their α-granules. However, recent developments in the field indicate that the role of platelets in fibrinolysis is much more diverse. Indeed, novel studies suggest that platelets form different subpopulations upon activation that play varied roles in regulating hemostasis...
February 19, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28213377/interventional-treatment-of-pulmonary-embolism
#6
David M Dudzinski, Jay Giri, Kenneth Rosenfield
Pulmonary embolism (PE) is a serious and prevalent cause of vascular disease. Nevertheless, optimal treatment for many phenotypes of PE remains uncertain. Treating PE requires appropriate risk stratification as a first step. For the highest-risk PE, presenting as shock or arrest, emergent systemic thrombolysis or embolectomy is reasonable, while for low-risk PE, anticoagulation alone is often chosen. Normotensive patients with PE but with indicia of right heart dysfunction (by biomarkers or imaging) constitute an intermediate-risk group for whom there is controversy on therapeutic strategy...
February 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28211169/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects
#7
Jin Zhou, Jarema Kochan, Ophelia Yin, Vance Warren, Cynthia Zamora, George Atiee, Joseph Pav, Yasushi Orihashi, Vijay Vashi, Victor Dishy
BACKGROUND: Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low-molecular weight compound inhibiting the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), developed as a fibrinolysis enhancer for treatment of thromboembolic diseases. OBJECTIVES: This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040 in healthy subjects...
February 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28208199/systemic-thrombolytic-therapy-for-acute-pulmonary-embolism-who-is-a-candidate
#8
Stavros V Konstantinides, Stefano Barco
Pulmonary embolism (PE) is a major cause of both acute and long-term morbidity for a large number of patients worldwide, and massive PE is frequently fatal. Right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of PE. Patients with clinically overt RV failure, that is, with cardiogenic shock or persistent hypotension at presentation (acute high-risk PE), are clearly in need of immediate reperfusion treatment with systemic thrombolysis or, alternatively, surgical or catheter-directed techniques...
February 2017: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28207534/a-case-control-study-on-the-structural-equation-model-of-the-mechanism-of-coagulation-and-fibrinolysis-imbalance-in-chronic-schistosomiasis
#9
Aiping Le, Lunli Zhang, Wei Liu, Xiaopeng Li, Jianwei Ren, An Ning
A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28203100/from-amino-acids-polymers-antimicrobial-peptides-and-histones-to-their-possible-role-in-the-pathogenesis-of-septic-shock-a-historical-perspective
#10
Isaac Ginsburg, Peter Vernon van Heerden, Erez Koren
This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28202881/the-exercise-paradox-may-be-solved-by-measuring-the-overall-thrombotic-state-using-native-blood
#11
Hideo Ikarugi, Junichiro Yamamoto
While exercise is widely believed to prevent atherothrombotic diseases, it occasionally causes sudden death. This exercise paradox may be due to the inadequate testing of the thrombotic and thrombolytic status. A recently developed shear-induced thrombosis/endogenous fibrinolysis test performed with non-anticoagulated blood samples allows the assessment of the thrombotic state of an individual both at rest and after exercise. This sensitive and physiologically relevant test may help to solve the aforementioned exercise paradox...
February 14, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28188400/-juvenile-stroke-what-is-important
#12
M Fischer, B Eckert, J Röther
Stroke in young adults is a diagnostic and therapeutic challenge for all persons involved. Approximately 15% of ischemic strokes occur in young adults. Lack of awareness of the symptoms in emergency departments often results in delayed diagnosis and access to specific therapeutic options, such as revascularization. The causes are often heterogeneous and necessitate specific investigations. The etiology of juvenile stroke includes drug abuse, vasculitis and arteriopathies, such as reversible vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although the prevalence of classical vascular risk factors is high...
February 10, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28186689/enhanced-mrna-expression-of-plasminogen-activator-inhibitor-1-in-livedoid-vasculopathy-lesions
#13
Mehmet Agirbasli, Fatih Göktay, Irem Peker, Pembegul Gunes, Fugen Vardar Aker, Mustafa Akkiprik
AIM: Thrombosis and inflammation play an important role in pathophysiology of livedoid vasculopathy (LV). Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of fibrinolysis and is a pivotal modulator in a broad range of biological processes. METHOD: The study specimens were retrospectively selected from archives of pathology department. We investigated PAI-1 mRNA expression in the paraffin blocks of patients with biopsy proven LV and controls...
February 10, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28179388/disseminated-intravascular-coagulation-like-reaction-following-rituximab-infusion
#14
Hind Rafei, Samah Nassereddine, Ivan F Garcia
Rituximab generally is a well-tolerated medication used in a variety of haematological and autoimmune conditions. The safety profile of the medication has been reviewed in the literature. Infusion reactions due to cytokine release are the most common side effects. With the increased use of rituximab, there is an increase incidence of cytopenias, most commonly thrombocytopenia and leucopenia. Coagulopathy is quite rare, reported previously in four cases in the literature. We highlighted the clinical course of a 39-year-old patient with precursor B-cell acute lymphoblastic leukaemia who was started on rituximab infusion...
February 8, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28176468/correlation-of-pre-operative-plasma-protein-concentrations-in-cardiac-surgery-patients-with-bleeding-outcomes-using-a-targeted-quantitative-proteomics-approach
#15
Nathan Clendenen, Ashley Tollefson, Monika Dzieciatkowska, Alice Cambiaghi, Manuela Ferrario, Miranda Kroehl, Anirban Banerjee, Angelo D'Alessandro, Kirk C Hansen, Nathaen Weitzel
PURPOSE: Despite recent advancements in the use of thrombelastography (TEG) in the surgical setting, adequate technology to accurately predict bleeding phenotypes for patients undergoing cardiopulmonary bypass on the basis of non-mechanical parameters is lacking. While basic science and translational studies have provided key mechanistic insights about the protein components of coagulation cascades and regulatory mediators of hemostasis and fibrinolysis, targeted protein assays are still missing and the association of protein profiles to bleeding phenotypes and TEG readouts have yet to be discovered...
February 8, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28174415/comparison-of-enoxaparin-and-rivaroxaban-in-balance-of-anti-fibrinolysis-and-anticoagulation-following-primary-total-knee-replacement-a-pilot-study
#16
Jinwei Xie, Jun Ma, Qiang Huang, Chen Yue, Fuxing Pei
BACKGROUND This study aimed to assess whether the efficacy of tranexamic acid (TXA) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement (TKR). It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin. MATERIAL AND METHODS A randomized clinical trial was conducted on 194 patients undergoing primary TKR for osteoarthritis. An intravenous dose of 15 mg/kg (TXA) and 1 g topical TXA were used. Patients randomly received enoxaparin or rivaroxaban prophylaxis when the drainage was less than 30 ml/h 6-8 h postoperatively...
February 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28169119/reperfusion-therapy-of-myocardial-infarction-in-mexico-a-challenge-for-modern-cardiology
#17
Carlos Martínez-Sánchez, Alexandra Arias-Mendoza, Héctor González-Pacheco, Diego Araiza-Garaygordobil, Luis Alfonso Marroquín-Donday, Jorge Padilla-Ibarra, Carlos Sierra-Fernández, Alfredo Altamirano-Castillo, Amada Álvarez-Sangabriel, Francisco Javier Azar-Manzur, José Luis Briseño-de la Cruz, Salvador Mendoza-García, Yigal Piña-Reyna, Marco Antonio Martínez-Ríos
Mexico has been positioned as the country with the highest mortality attributed to myocardial infarction among the members of the Organization for Economic Cooperation and Development. This rate responds to multiple factors, including a low rate of reperfusion therapy and the absence of a coordinated system of care. Primary angioplasty is the reperfusion method recommended by the guidelines, but requires multiple conditions that are not reached at all times. Early pharmacological reperfusion of the culprit coronary artery and early coronary angiography (pharmacoinvasive strategy) can be the solution to the logistical problem that primary angioplasty rises...
February 3, 2017: Archivos de Cardiología de México
https://www.readbyqxmd.com/read/28169020/description-of-stroke-mimics-after-complete-neurovascular-assessment
#18
C Avellaneda-Gómez, A Rodríguez Campello, E Giralt Steinhauer, A Gómez González, M Serra Martínez, P de Ceballos Cerrajería, A Zabalza de Torres, E Cuadrado-Godia, A Ois Santiago, J Jiménez-Conde, J Roquer
INTRODUCTION: A considerable percentage of events initially diagnosed as ischaemic stroke have non-cerebrovascular causes; these are called stroke mimics (SM). Currently available evidence about these events is heterogeneous and comes from studies with small samples. OBJECTIVE: The purpose of our study is to identify conditions that may present as SM, define their epidemiological and clinical characteristics, and determine the percentage of cases of SM treated with intravenous fibrinolysis...
February 4, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28166602/managing-the-precarious-hemostatic-balance-during-extracorporeal-life-support-implications-for-coagulation-laboratories
#19
Anne M Winkler
For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure unresponsive to medical management, and there are increasing numbers of centers performing ECLS for numerous indications worldwide. Despite the progress with advancing technology, hemorrhagic and thrombotic complications occur frequently and are associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and a nonendothelialized circuit, there is activation of coagulation, fibrinolysis, as well as an increased inflammatory response; thus, anticoagulation of the patient and circuit is necessary...
February 6, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28164653/blast-burn-combined-injury-followed-by-immediate-seawater-immersion-induces-hemodynamic-changes-and-metabolic-acidosis-an-experimental-study-in-a-canine-model
#20
Yi Hu, Qingxiang Mao, Shaobing Ye, Ji Peng, Xiaoqin Gan, Xian Chen, Hong Yan
BACKGROUND: Severe burn-blast combined injury often causes systematic dysfunction related to blood coagulation, anticoagulation, and fibrinolysis. However, studies of burn-blast combined injury followed by immersion in seawater are rarely reported. METHODS: A canine burn-blast combined injury model was established including blast injury caused by explosion immediately followed by burning with gelatinized gasoline flames. The dogs were randomly divided into four groups: burn-blast injury (BB group); burn-blast injury followed by seawater immersion for four hours (BBI group); only immersed in seawater (I group); and sham treatment with no injury or immersion (S group)...
July 1, 2016: Clinical Laboratory
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