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Fibrinolysis

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https://www.readbyqxmd.com/read/28925023/fibrinolysis-from-blood-to-the-brain
#1
Robert L Medcalf
We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28923772/reference-intervals-of-citrated-native-whole-blood-thromboelastography-in-premature-neonates
#2
Mario Motta, Brunetta Guaragni, Elena Pezzotti, Carmen Rodriguez-Perez, Gaetano Chirico
BACKGROUND: Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated...
September 15, 2017: Early Human Development
https://www.readbyqxmd.com/read/28921408/catheter-ablation-for-af-improves-global-thrombotic-profile-and-enhances-fibrinolysis
#3
Maria Niespialowska-Steuden, Vias Markides, Mohamed Farag, David Jones, Wajid Hussain, Tom Wong, Diana A Gorog
Patients with atrial fibrillation (AF) are at increased risk of thrombotic events despite oral anticoagulation (OAC). Radiofrequency catheter ablation (RFCA) can restore and maintain sinus rhythm (SR) in patients with AF. To assess whether RFCA improves thrombotic status. 80 patients (71% male, 64 ± 12y) with recently diagnosed AF, on OAC and scheduled to undergo RFCA or DC cardioversion (DCCV) were recruited. Thrombotic status was assessed using the point-of-care global thrombosis test (GTT), before, and 4-6 weeks after DCCV and 3 months after RFCA...
September 18, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28920104/variable-phenotypic-penetrance-of-thrombosis-in-adult-mice-after-tissue-selective-and-temporally-controlled-thbd-gene-inactivation
#4
Thijs E van Mens, Hai-Po H Liang, Sreemanti Basu, Irene Hernandez, Mark Zogg, Jennifer May, Min Zhan, Qiuhui Yang, Jamie Foeckler, Shawn Kalloway, Rashmi Sood, Caren Sue Karlson, Hartmut Weiler
Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/28918481/fibrinolysis-in-trauma-a-review
#5
REVIEW
M J Madurska, K A Sachse, J O Jansen, T E Rasmussen, J J Morrison
Fibrinolytic dysregulation is an important mechanism in traumatic coagulopathy. It is an incompletely understood process that consists of a spectrum ranging from excessive breakdown (hyperfibrinolysis) and the shutdown of fibrinolysis. Both hyperfibrinolysis and shutdown are associated with excess mortality and post-traumatic organ failure. The pathophysiology appears to relate to endothelial injury and hypoperfusion, with several molecular markers identified in playing a role. Although there are no universally accepted diagnostic tests, viscoelastic studies appear to offer the greatest potential for timely identification of patients presenting with fibrinolytic dysregulation...
September 16, 2017: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
https://www.readbyqxmd.com/read/28914713/the-hyperfibrinolytic-phenotype-is-the-most-lethal-and-resource-intense-presentation-of-fibrinolysis-in-massive-transfusion-patients
#6
John R Taylor, Erin E Fox, John B Holcomb, Sandro Rizoli, Kenji Inaba, Martin A Schreiber, Karen Brasel, Thomas M Scalea, Charles E Wade, Eileen Bulger, Bryan A Cotton
BACKGROUND: Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, while shutdown (SD) patients would have the greatest complication burden. METHODS: Severely injured patients predicted to receive a massive transfusion at 12 level-1 trauma centers were randomized to one of two transfusion ratios as described in the PROPPR trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0...
September 13, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28914172/effects-of-pharmacological-inhibition-of-plasminogen-binding-on-liver-regeneration-in-rats
#7
Atsushi Miura, Kyoko Ishiguro, Kouta Koizumi, Yuki Yaita, Yori Ozaki-Masuzawa, Takashi Hosono, Taiichiro Seki
The fibrinolysis system is thought to play an important role in liver regeneration. We previously found that plasminogen (Plg) is localized to the cell surface of regenerating liver tissue as well as proliferating hepatocytes in vitro. Here, we investigated the significance of Plg binding to the cell surface during liver regeneration. Pre-administration of tranexamic acid (TXA), which is a competitive inhibitor of Plg binding, to hepatectomized rats mildly delayed restoration of liver weight in vivo. Although binding of Plg to the cell membrane decreased following TXA administration, TXA showed little effect on hepatocyte proliferation in rats...
September 15, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28913590/challenges-of-anticoagulation-therapy-in-pregnancy
#8
REVIEW
Annemarie E Fogerty
Thrombotic complications in pregnancy represent a major cause of morbidity and mortality. Pregnancy is a primary hypercoagulable state due to enhanced production of clotting factors, a decrease in protein S activity, and inhibition of fibrinolysis. These physiologic changes will yield a collective rate of venous thromboembolism (VTE) of about 1-2 in 1000 pregnancies for the general obstetric population, which represents a five- to tenfold increased risk in pregnancy compared to age-matched non-pregnant peers...
September 14, 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28911285/in-vitro-evaluation-of-the-effect-of-haemodilution-with-dextran-40-on-coagulation-profile-as-measured-by-thromboelastometry-and-multiple-electrode-aggregometry
#9
Pca Kam, Jpc Liou, Kxf Yang
We evaluated the effects of haemodilution with either dextran 40 or 0.9% normal saline on coagulation in vitro using rotational thromboelastometry (ROTEM®, Pentapharm Co., Munich, Germany) and multiple electrode aggregometry (Multiplate® Platelet Function Analyser, Dynabyte, Munich, Germany). Venous blood samples obtained from 20 healthy volunteers were diluted in vitro with dextran 40 or normal saline by 5%, 10% and 15%. Fibrinogen concentration, ROTEM-EXTEM® (screening test for the extrinsic coagulation pathway), FIBTEM® (an EXTEM-based assay of the fibrin component of clot) parameters including coagulation time, clot formation time, alpha angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each level of haemodilution...
September 2017: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/28904799/clinical-significance-of-measuring-plasminogen-activator-inhibitor-1-in-sepsis
#10
Toshiaki Iba, Jecko Thachil
BACKGROUND: Disseminated thrombotic process in the microcirculation is considered to be an important cause of multiple organ dysfunction in sepsis. The fundamental purpose of this prothrombotic change was believed to be in the host defense against microbial dissemination. In that process, antifibrinolytic property plays an important role. MAIN BODY: For the understanding of pathophysiology of sepsis, it is quite useful to grasp the alterations in coagulation/fibrinolytic parameters, i...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28904504/role-of-serpine-gene-polymorphism-in-recurrent-implantation-failure-and-preeclampsia
#11
Nidhi Sharma, Jayashree K Srinivasan, Margeret Harriet Priya, Venkatachalam Sibiya
This is a rare case of serpine gene polymorphism causing thrombophilia and recurrent implantation failure following intrauterine insemination. SERPINE1 gene encodes plasminogen activator inhibitor type 1 and inhibits fibrinolysis, or clot dissolution. The 4G variant results in increased expression of SERPINE1 and consequently higher inhibition of fibrinolysis, thus leading to thrombophilia. The patient had unexplained primary infertility for 9 years. Ovulation induction was done with gonadotropin releasing hormone (GnRH) agonist long protocol...
April 2017: Journal of Human Reproductive Sciences
https://www.readbyqxmd.com/read/28904290/copper-diethyldithiocarbamate-as-an-inhibitor-of-tissue-plasminogen-activator-synthesis-in-cultured-human-coronary-endothelial-cells
#12
Tomoya Fujie, Shiori Okino, Eiko Yoshida, Chika Yamamoto, Hiroshi Naka, Toshiyuki Kaji
Recent developments have shown that organic-inorganic hybrid molecules have the potential to provide useful tools for analyzing biological systems. In the case of fibrinolysis, which is the phenomenon whereby fibrin is degraded by plasmin that has been converted from plasminogen via tissue plasminogen activator (t-PA) secreted from vascular endothelial cells, we hypothesized that there may be organic-inorganic hybrid molecules that could be used to analyze the mechanisms by which endothelial fibrinolysis is regulated...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28903941/increased-hazard-of-myocardial-infarction-with-insulin-provision-therapy-in-actively-smoking-patients-with-diabetes-mellitus-and-stable-ischemic-heart-disease-the-bari-2d-bypass-angioplasty-revascularization-investigation-2-diabetes-trial
#13
Asrar A Khan, Matthew J Chung, Eric Novak, David L Brown
BACKGROUND: In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (IP) therapy, as opposed to insulin sensitization (IS) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (MI)...
September 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28902964/plasmatic-coagulation-and-fibrinolysis-in-healthy-and-otostrongylus-affected-northern-elephant-seals-mirounga-angustirostris
#14
Sarrah Kaye, Shawn Johnson, Carlos Rios, Daniel J Fletcher
BACKGROUND: Prepatent Otostrongylus arteritis results in hemorrhagic diathesis in free-ranging Northern elephant seals (Mirounga angustirostris) attributed to aberrant larval migration of the lungworm, Otostrongylus circumlitus. Clinical signs are often nonspecific, including lethargy, anorexia, and blepharospasm, but can progress to spontaneous frank hemorrhage and death within 72 hours of onset. Previously published case reports describe coagulopathy with prolonged PT and APTT, normal to elevated platelet counts, normal antithrombin concentrations, and low concentrations of fibrinogen degradation products...
September 13, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28895444/d-dimer-elevation-as-a-blood-biomarker-for-detection-of-structural-disorder-in-mild-traumatic-brain-injury
#15
Kazutaka Sugimoto, Eiichi Suehiro, Mizuya Shinoyama, Hirokazu Sadahiro, Kouhei Haji, Yuichi Fujiyama, Reo Kawano, Mitsuaki Nishioka, Michiyasu Suzuki
Computed tomography (CT) scans are useful in patients with traumatic brain injury (TBI), but the potential risks associated with ionizing radiation are unknown. Furthermore, CT scans are not commonly available in developing countries. In this study, coagulopathy and abnormal fibrinolysis were investigated as blood biomarkers for detection of structural disorder in mild TBI. A total of 88 patients with mild and isolated TBI (Glasgow Coma Scale (GCS) score 14-15) were admitted to Kenwakai Ootemachi Hospital between October 2014 and March 2016...
September 12, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28895372/-tipping-extracellular-matrix-remodelling-towards-regression-of-liver-fibrosis-novel-concepts
#16
Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, as well as other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC)...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28893232/plasminogen-activator-inhibitor-1-deficiency-enhances-subchondral-osteopenia-after-induction-of-osteoarthritis-in-mice
#17
Akihiro Moritake, Naoyuki Kawao, Kiyotaka Okada, Kohei Tatsumi, Masayoshi Ishida, Katsumi Okumoto, Osamu Matsuo, Masao Akagi, Hiroshi Kaji
BACKGROUND: Subchondral osteopenia is important for the pathophysiology of osteoarthritis (OA). Although previous studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown. We therefore investigated the roles of PAI-1 in the subchondral bone in OA model mice. METHODS: Wild type (WT) and PAI-1-deficient (KO) mice were ovariectomized (OVX), and then destabilization of the medial meniscus (DMM) surgery was performed...
September 11, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28891082/thrombolysis-for-massive-pulmonary-embolism-in-pregnancy
#18
Mojdeh S Heavner, Min Zhang, Chelsea E Bast, Lindsey Parker, Rachel F Eyler
Pregnant women are at high risk for venous thromboembolism, including pulmonary embolism (PE), given expected changes in coagulation, fibrinolysis, and venous blood flow. In fact, PE is the leading cause of maternal death in the United States. Non-pregnant patients who develop PE with hypotension or showing signs of deterioration after anticoagulation receive thrombolytics as a standard of care. Pregnant women, however, have been excluded from clinical trials with thrombolytics and all data available in this population is published as case reports or case series...
September 11, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28890533/dose-response-relationship-between-thrombin-activatable-fibrinolysis-inhibitor-tafi-and-stroke-a-chinese-case-control-study
#19
Huixu Dai, Jingpu Shi, Qiao He, Hao Sun
BACKGROUND Because TAFI (thrombin-activatable fibrinolysis inhibitor) antigen varies widely among different populations, we performed this case-control study to explore the relationship between TAFI levels and stroke in a Chinese population. MATERIAL AND METHODS Our population-based case-control study included 217 stroke patients and 218 healthy controls. The plasma TAFI level was measured by immune turbidimetry. Univariate and multivariate logistic regression analyses were used to analyze the association between different TAFI levels and stroke and its subtypes...
September 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28887505/impaired-fibrinolysis-and-lower-levels-of-plasma-%C3%AE-2-macroglobulin-are-associated-with-an-increased-risk-of-severe-asthma-exacerbations
#20
Stanislawa Bazan-Socha, Lucyna Mastalerz, Agnieszka Cybulska, Lech Zareba, Romy Kremers, Michal Zabczyk, Grazyna Pulka, Teresa Iwaniec, Jan G Bazan, Coenraad Hemker, Anetta Undas
Recently we have reported that asthma is associated with enhanced plasma thrombin formation, impaired fibrinolysis and platelet activation. In the present study we investigated whether described prothrombotic blood alterations might predispose to thromboembolic events or asthma exacerbations. In 164 adult asthmatics we assessed clinical events during 3-year follow-up and analyzed their associations with measured at baseline prothrombotic blood parameters. Data were obtained from 157 (95.7%) of the asthma patients...
September 8, 2017: Scientific Reports
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