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Fibrinolysis stroke

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https://www.readbyqxmd.com/read/28797689/can-the-benefits-of-rtpa-treatment-for-stroke-be-improved
#1
REVIEW
D Vivien
Tissue-type plasminogen activator (tPA) is a serine protease well known to promote fibrinolysis. This is why: its recombinant form (rtPA) can be used, either alone or combined with thrombectomy, to promote recanalization/reperfusion following ischemic stroke. However, its overall benefits are counteracted by some of its side-effects, including incomplete lysis of clots, an increased risk of hemorrhagic transformation and the possibility of neurotoxicity. Nevertheless, better understanding of the mechanisms by which tPA influences brain function and promotes its alteration may help in the design of new strategies to improve stroke therapy...
August 7, 2017: Revue Neurologique
https://www.readbyqxmd.com/read/28775073/clots-are-potent-triggers-of-inflammatory-cell-gene-expression-indications-for-timely-fibrinolysis
#2
Robert A Campbell, Adriana Vieira-de-Abreu, Jesse W Rowley, Zechariah G Franks, Bhanu Kanth Manne, Matthew T Rondina, Larry W Kraiss, Jennifer J Majersik, Guy A Zimmerman, Andrew S Weyrich
OBJECTIVE: Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. Determine whether clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases. APPROACH AND RESULTS: We performed next-generation RNA sequencing on monocytes extracted from whole blood clots and using a purified plasma clot system...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28741405/optimized-tpa-a-non-neurotoxic-fibrinolytic-agent-for-the-drainage-of-intracerebral-hemorrhages
#3
Romain Goulay, Mikaël Naveau, Thomas Gaberel, Denis Vivien, Jérôme Parcq
Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28730407/venous-thromboembolism-thrombosis-inflammation-and-immunothrombosis-for-clinicians
#4
REVIEW
Eduardo Vazquez-Garza, Carlos Jerjes-Sanchez, Aline Navarrete, Jorge Joya-Harrison, David Rodriguez
Venous thromboembolism (VTE) is a worldwide disease related with mortality, cardiovascular disability, impaired quality of life and, cause major long-term complications. Clinicians related to the acute and long-term patients care must be involved in the molecular mechanisms of thrombosis. The vessel wall and its inner lining of the endothelium are critical to the maintenance of a patent vasculature. After endothelial disruption, collagen (first line of endothelial defense) and intravascular tissue factor (second line of endothelial defense) are exposed to blood flow, starting the formation of a thrombus...
July 20, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28684538/tissue-type-plasminogen-activator-regulates-macrophage-activation-and-innate-immunity
#5
Elisabetta Mantuano, Pardis Azmoon, Coralie Brifault, Michael A Banki, Andrew S Gilder, Wendy M Campana, Steven L Gonias
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell-signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires LDL Receptor-related Protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IκBα phosphorylation. tPA independently induced transient IκBα phosphorylation and ERK1/2 activation in macrophages; however, these events that did not trigger inflammatory mediator expression...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28663010/intravenous-fibrinolysis-in-ischemic-stroke-of-large-vessel-after-reversing-effect-of-dabigatran-with-idarucizumab
#6
Gary Alvarez Bravo, Emilio Orts Castro, Guilherme Carvalho Monteiro, Ignacio López Zuazo
Currently the use of idarucizumab to reverse the effect of dabigatran emerges as a possibility of treatment for those patients who present with an ischemic stroke despite taking this anticoagulant. We present our experience regarding the use of intravenous tissue plasminogen activator in a patient with ischemic stroke due to complete occlusion of the left middle cerebral artery after blocking the effect of dabigatran with idarucizumab and whose result was an almost total improvement of the neurologic deficit...
September 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28571619/elevated-nt-probnp-is-associated-with-unfavorably-altered-plasma-fibrin-clot-properties-in-atrial-fibrillation
#7
Paweł T Matusik, Patrycja S Matusik, Zdzisława Kornacewicz-Jach, Barbara Małecka, Andrzej Ząbek, Anetta Undas
BACKGROUND: Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. METHODS AND RESULTS: We investigated plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years)...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28552276/adjuncts-to-blood-component-therapies-for-the-treatment-of-bleeding-in-the-intensive-care-unit
#8
REVIEW
Jerrold H Levy, Kamrouz Ghadimi, Quintin J Quinones, Raquel R Bartz, Ian Welsby
Patients who are critically ill following surgical or traumatic injury often present with coagulopathy as a component of the complex multisystem dysfunction that clinicians must rapidly diagnose and treat in the intensive care environment. Failure to recognize coagulopathy while volume resuscitation with crystalloid or colloid takes place, or an unbalanced transfusion strategy focused on packed red blood cell transfusion can all significantly worsen coagulopathy, leading to increased transfusion requirements and poor outcomes...
April 25, 2017: Transfusion Medicine Reviews
https://www.readbyqxmd.com/read/28546044/endovascular-repair-of-thoraco-abdominal-and-arch-aneurysms-in-patients-with-connective-tissue-disease-using-branched-and-fenestrated-devices
#9
Rachel E Clough, Teresa Martin-Gonzalez, Katrien Van Calster, Adrien Hertault, Rafaëlle Spear, Richard Azzaoui, Jonathan Sobocinski, Stéphan Haulon
INTRODUCTION: Prophylactic open surgery is the standard practice in patients with connective tissue and thoraco-abdominal (TAAA) and aortic arch disease. Branched and fenestrated devices offer a less invasive alternative but there are concerns regarding the durability of the repair and the effect of the stent graft on the fragile aortic wall. The aim of this study was to evaluate mid-term outcomes of fenestrated and/or branched endografting in patients with connective tissue disease. METHODS: All patients with connective tissue disease that underwent TAAA or arch aneurysm repair using a fenestrated and/or branched endograft in a single high volume centre between 2004 and 2015 were included...
May 22, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28515757/emergency-heartware-ventricular-assist-device-hvad-exchange-due-to-pump-thrombosis-using-minimally-invasive-technique
#10
Remigiusz Antończyk, Ewa Trejnowska, Jerzy Pacholewicz, Tomasz Wolny, Paweł Nadziakiewicz, Karolina Antończyk, Izabela Copik, Magdalena Piontek, Małgorzata Jasińska, Krzysztof Filipiak, Maciej Głowacki, Maciej Gawlikowski, Marcin Borowicz, Roman Kustosz, Jacek Waszak, Piotr Przybyłowski, Marian Zembala, Michał Zakliczyński, Michał Oskar Zembala
Left ventricular assist device (LVAD) thrombosis remains a dreadful complication of mechanical circulatory support, with an incidence of 8-12% depending on the pump type and patient's comorbidities. Fibrinolysis may be considered early in pump thrombosis, but when contraindicated a pump exchange remains the only alternative. This short report documents an emergency LVAD exchange in a 55-year-old man who underwent LVAD (HeartWare Inc) implantation in 2013 as a bridge to transplantation. Four months after the initial surgery, he suffered from a hemorrhagic stroke despite properly managed anticoagulation...
March 2017: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
https://www.readbyqxmd.com/read/28506697/inflammation-and-hemostasis-in-older-octogenarians-implication-in-5-year-survival
#11
Judit Cubedo, Teresa Padró, Francesc Formiga, Assumpta Ferrer, Glòria Padrós, Esther Peña, Lina Badimon
Social changes and medical advances have increased longevity, but the conditions governing healthy vs unhealthy cardiovascular (CV) aging are not fully known. Factors beyond classical CV risk factors may have an important unrecognized value. We sought to identify proteins differentially expressed in healthy octogenarians (HOs) without a history of cardiovascular disease (CVD) and preserved functional and cognitive state compared with octogenarians with a history of CVD and cognitive decline (UHOs) using a systems biology approach, and investigated how these proteins relate to CV mortality at 5-year follow-up...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28472252/new-insights-into-the-role-of-adipose-tissue-in-thrombosis
#12
Gemma Vilahur, Soumaya Ben-Aicha, Lina Badimon
Central obesity is independently associated with an elevated risk of cardiovascular disease, particularly thrombotic complications. Increasing data supports a link between excess body weight and the risk to suffer acute myocardial infarction, stent thrombosis after percutaneous interventions, ischemic stroke and vein thrombosis.Experimental and in vitro data have provided insights as to the mechanisms currently presumed to increase the thrombotic risk in obese subjects. Obesity is characterized by a chronic low grade inflammation and systemic oxidative stress that eventually damage the endothelium losing its antithrombotic properties...
May 3, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28472090/test-repositioning-for-functional-assessment-of-neurological-outcome-after-experimental-stroke-in-mice
#13
Macarena Hernández-Jiménez, Carolina Peña-Martínez, María Del Carmen Godino, Jaime Díaz-Guzmán, María Ángeles Moro, Ignacio Lizasoain
Stroke is a cerebrovascular pathology for which the only approved treatment is fibrinolysis. Several studies have focused on the development of new drugs but none has led to effective therapies to date, due, among others, to the difficulty to evaluate clinical deficits in experimental animal models. The present study aims to explore the applicability of known behavioral tests not commonly used in ischemia for the neurological assessment of mice after experimental stroke in different brain areas. A total of 225 CD1 male mice were randomly assigned to permanent middle cerebral artery occlusion by ligature (pMCAO) or permanent anterior cerebral artery occlusion by photothrombosis (pACAO) models...
2017: PloS One
https://www.readbyqxmd.com/read/28382369/fibrin-clot-characteristics-in-acute-ischaemic-stroke-patients-treated-with-thrombolysis-the-impact-on-clinical-outcome
#14
Jan P Bembenek, Maciej Niewada, Jakub Siudut, Krzysztof Plens, Anna Członkowska, Anetta Undas
Fibrin clot properties in acute ischaemic stroke (AIS) are unfavourably altered, including faster formation of denser and poorly lysable fibre networks. We investigated clot properties in AIS patients treated with recombinant tissue plasminogen activator (rtPA) and their impact on clinical outcome. In 74 consecutive AIS patients eligible for rtPA treatment, we assessed ex vivo plasma fibrin clot formation, permeability (Ks), and rtPA-induced lysis, along with peak thrombin generation, fibrinolysis proteins and inhibitors at three time points - on admission, after 24 hours and 3 months since stroke...
June 28, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28378106/plasminogen-activator-inhibitor-links-obesity-and-thrombotic-cerebrovascular-diseases-the-roles-of-pai-1-and-obesity-on-stroke
#15
REVIEW
Rui Chen, Jinchuan Yan, Peijing Liu, Zhongqun Wang, Cuiping Wang
One of the global socioeconomic phenomena occurred during the last decades is the increased prevalence of obesity, with direct consequence on the risk of developing thrombotic disorders. As the physiological inhibitor of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) is well known for its role in fibrinolysis. More and more evidences have shown that PAI-1 involves in physiopathologic mechanisms of many diseases and metabolic disorder. Increased serum level of PAI-1 has been observed in obesity and it also contributes to the development of adipose tissue and then has effects on obesity...
June 2017: Metabolic Brain Disease
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
#16
J Zhou, J Kochan, O Yin, V Warren, C Zamora, G Atiee, J Pav, Y Orihashi, V Vashi, V Dishy
Essentials DS-1040 inhibits the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa). Infusion of DS-1040 was safe and well tolerated in healthy young and elderly subjects. DS-1040 substantially decreased TAFIa activity but had no impact on bleeding time. DS-1040 may provide an option of safer thrombolytic therapy. SUMMARY: Background Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue-type plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding...
May 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28188400/-juvenile-stroke-what-is-important
#17
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/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/28116631/translational-initiatives-in-thrombolytic-therapy
#19
REVIEW
Melvin E Klegerman
Once thrombi have formed as part of the pathology defining myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis or other embolic disorders, the only clinically meaningful thrombolytic agents available for reversing the thrombogenic process are various plasminogen activators. These agents are enzymes that reverse fibrin polymerization underlying the coagulation process by converting endogenous plasminogen to plasmin, which cleaves the fibrin network to form increasingly smaller protein fragments, a process known as fibrinolysis...
January 23, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28089539/reperfusion-therapy-in-patients-with-acute-ischaemic-stroke-caused-by-cervical-artery-dissection
#20
L A Crespo Araico, R Vera Lechuga, A Cruz-Culebras, C Matute Lozano, A de Felipe Mimbrera, P Agüero Rabes, E Viedma Guiard, C Estévez Fraga, J Masjuan Vallejo
INTRODUCTION: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. METHODS: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. RESULTS: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43...
January 12, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
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