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Coagulation Factor

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https://www.readbyqxmd.com/read/29222320/anticoagulation-with-vads-and-ecmo-walking-the-tightrope
#1
REVIEW
Leslie Raffini
The evolution of devices for mechanical circulatory support (MCS), including ventricular assist devices (VADs) for patients with heart failure and extracorporeal membrane oxygenation (ECMO) for patients with acute cardiac or respiratory failure, has improved survival for subsets of critically ill children and adults. The devices are intricate and complex, allowing blood to bypass the heart or lungs (or both). As blood flows through these artificial devices, normal hemostasis is disrupted, coagulation is promoted, and in the absence of anticoagulation, a thrombus may form in the device, resulting in device failure or embolic stroke...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222310/novel-alternate-hemostatic-agents-for-patients-with-inhibitors-beyond-bypass-therapy
#2
REVIEW
Margaret V Ragni
Inhibitor formation is among the most severe complications of hemophilia treatment. With a cumulative incidence of ∼30% in those with severe hemophilia A and ∼3% in those with severe hemophilia B, inhibitors are caused by a T-cell response directed against infused coagulation factor; these inhibitors neutralize factor VIII or IX activity and disrupt normal hemostasis. Inhibitor patients become unresponsive to standard factor treatment and, as an alternative, use bypass treatment (eg, recombinant factor VIIa or factor VIII inhibitor bypass activity)...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221978/influence-of-6-hydroxyethyl-starch-130-0-4-versus-crystalloid-solution-on-structural-renal-damage-markers-after-coronary-artery-bypass-grafting-a-post-hoc-subgroup-analysis-of-a-prospective-trial
#3
Thomas Datzmann, Markus Hoenicka, Helmut Reinelt, Andreas Liebold, Hagen Gorki
OBJECTIVE: The restriction of hydroxyethyl starch (HES) has mandated changes in volume management based on data of critically ill patients. Reliable data of structural renal damage after HES treatment in cardiac surgical patients are lacking. The influence of 6% HES 130/0.4 was investigated in this study. DESIGN: An exploratory post hoc subgroup analysis of a prospective trial was performed. SETTING: The study was carried out at a university hospital...
May 25, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29220362/optimized-plasma-preparation-is-essential-to-monitor-platelet-stored-molecules-in-humans
#4
Marion Mussbacher, Waltraud C Schrottmaier, Manuel Salzmann, Christine Brostjan, Johannes A Schmid, Patrick Starlinger, Alice Assinger
Platelets store a plethora of different molecules within their granules, modulating numerous pathways, not only in coagulation, but also in angiogenesis, wound healing, and inflammatory diseases. These molecules get rapidly released upon activation and therefore represent an easily accessible indirect marker for platelet activation. Accurate analysis of platelet-derived molecules in the plasma requires appropriate anticoagulation to avoid in vitro activation and subsequent degranulation of platelets, potentially causing artificially high levels and masking biologically relevant differences within translational research studies...
2017: PloS One
https://www.readbyqxmd.com/read/29219827/venous-thrombosis-and-coagulation-parameters-in-patients-with-pure-venous-malformations
#5
J van Es, N A Kappelhof, R A Douma, J C M Meijers, V E A Gerdes, C M A M van der Horst
INTRODUCTION: Venous malformations (VMs) are ubiquitous, low-flow vascular anomalies known to be occasionally painful due to thrombotic episodes within the lesion. The prevalence of superficial or deep vein thrombosis is unclear. METHODS: A cross-sectional study among outpatients aged ≥ 12 years with pure VMs was performed, quantifying the prevalence of thrombosis by screening all patients with compression ultrasonography (CUS). Additionally, we evaluated whether coagulation alterations were related to thrombosis observed with CUS...
October 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29217770/protein-c-receptor-stimulates-multiple-signaling-pathways-in-breast-cancer-cells
#6
Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and trans-activation of insulin-like growth factor 1 receptor (IGF-1R)...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217135/microrna-145-impedes-thrombus-formation-via-targeting-tissue-factor-in-venous-thrombosis
#7
Anita Sahu, Prabhash Kumar Jha, Amit Prabhakar, Heisnam Dinesh Singh, Neha Gupta, Tathagata Chatterjee, Tarun Tyagi, Swati Sharma, Babita Kumari, Somnath Singh, Velu Nair, Shailendra Goel, Mohammad Zahid Ashraf
Venous thromboembolism (VTE), the third leading cardiovascular complication, requires more understanding at molecular levels. Here, we have identified miR-145 as a key molecule for regulating thrombus formation in venous thrombosis (VT) employing network based bioinformatics approach and in vivo experiments. Levels of miR-145 showed an inverse correlation with thrombus load determined by coagulation variables. MiRNA target prediction tools and in vitro study identified tissue factor (TF) as a target gene for miR-145...
November 23, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29216953/-significance-of-heparin-in-the-treatment-of-patients-with-sepsis
#8
Qinlong Sun, Erzhen Chen
The latest definition of sepsis (Sepsis-3) is the life-threatening organ dysfunction due to overreaction of immune system caused by infection. The situation can develop into multiple organ dysfunction syndromes (MODS). In the pathological process of pathogen invasion, a large number of inflammatory factors directly damage organ function, while dysfunction of coagulation system is also involved in this process. With the overreaction of inflammation, disseminated intravascular coagulation (DIC) occurred, which further exacerbated organ damage...
December 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29215847/-pathogenic-peculiarities-of-disseminated-intravascular-coagulation-of-various-ethiology
#9
E V Guzovskaya, S N Serebrennikova
DIC is a severe complication, often resulting in multi-organ failure and fatal outcome. As any syndrome, it is polyethiologic, while a big number of its causes logically leads to various mechanisms of its forming. Main manifestations of the disseminated intravascular blood coagulation syndrome are clottage and haemorrhage. A result of a massive clottage in microcirculatory bed of internal organs is development of dystrophic changes in them and organ failure. Haemorrhage in its turn, results in decreased volume of circulating blood, arterial hypotension and hemic hypoxia, in most severe cases leading to the fatal outcome...
April 2017: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
https://www.readbyqxmd.com/read/29215061/local-production-of-activated-factor-x-in-atherosclerotic-plaque-induced-vascular-smooth-muscle-cell-senescence
#10
Fumihiro Sanada, Jun Muratsu, Rei Otsu, Hideo Shimizu, Nobutaka Koibuchi, Kazutaka Uchida, Yoshiaki Taniyama, Shinichi Yoshimura, Hiromi Rakugi, Ryuichi Morishita
Our previous study demonstrated that coagulation factor Xa (FXa) induced endothelial cell senescence, resulting in inflammation and impaired angiogenesis. This mechanism is dictated through protease-activated receptors, PARs, insulin-like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs contributes to the pathophysiology of several chronic inflammatory diseases, including atherosclerosis. Thus, we speculated that similar mechanism might participate in the progression of atherosclerotic plaques...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29215036/proteomics-and-antivenomics-of-echis-carinatus-carinatus-venom-correlation-with-pharmacological-properties-and-pathophysiology-of-envenomation
#11
Aparup Patra, Bhargab Kalita, Abhishek Chanda, Ashis K Mukherjee
The proteome composition of Echis carinatus carinatus venom (ECV) from India was studied for the first time by tandem mass spectrometry analysis. A total of 90, 47, and 22 distinct enzymatic and non-enzymatic proteins belonging to 15, 10, and 6 snake venom protein families were identified in ECV by searching the ESI-LC-MS/MS data against non-redundant protein databases of Viperidae (taxid 8689), Echis (taxid 8699) and Echis carinatus (taxid 40353), respectively. However, analysis of MS/MS data against the Transcriptome Shotgun Assembly sequences (87 entries) of conger E...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214439/a-pharmacometric-approach-to-substitute-for-a-conventional-dose-finding-study-in-rare-diseases-example-of-phase-iii-dose-selection-for-emicizumab-in-hemophilia-a
#12
Koichiro Yoneyama, Christophe Schmitt, Naoki Kotani, Gallia G Levy, Ryu Kasai, Satofumi Iida, Midori Shima, Takehiko Kawanishi
BACKGROUND: Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg. METHODS: Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency...
December 6, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29214154/the-search-for-biomarkers-in-hereditary-angioedema
#13
REVIEW
Allen P Kaplan, Coen Maas
The unpredictable nature of attacks of tissue swelling in hereditary angioedema requires the identification of reliable biomarkers to monitor disease activity as well as response to therapy. At present, one can assess a C4 level (by ELISA) to assist in diagnosis but neither C4 nor C1 inhibitor levels reflect clinical course or prognosis. We will here review a collection of plasma proteins involved in blood coagulation, fibrinolysis, and innate immunity (Figure 1). A main focus is those proteins that are key to the formation of bradykinin (BK); namely, factor XII, plasma prekallikrein/kallikrein, high-molecular weight kininogen, and BK itself since overproduction of BK is key to the disease...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29213245/implication-of-free-fatty-acids-in-thrombin-generation-and-fibrinolysis-in-vascular-inflammation-in-zucker-rats-and-evolution-with-aging
#14
Jérémy Lagrange, Mélusine Didelot, Amel Mohamadi, Lucy A Walton, Saartje Bloemen, Bas de Laat, Huguette Louis, Simon N Thornton, Brian Derby, Michael J Sherratt, Bruno Fève, Pascal Challande, Riaz Akhtar, J Kennedy Cruickshank, Patrick Lacolley, Véronique Regnault
Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis. Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29212866/acquired-haemophilia-a-complicating-alemtuzumab-therapy-for-multiple-sclerosis
#15
Georgia McCaughan, Jennifer Massey, Ian Sutton, Jennifer Curnow
Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII...
December 5, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29212801/roles-of-high-mobility-group-box-1-and-thrombin-in-murine-pulmonary-fibrosis-and-the-therapeutic-potential-of-thrombomodulin
#16
Takashi Kida, Takahiro Seno, Hidetake Nagahara, Takuya Inoue, Amane Nakabayashi, Yuji Kukida, Kazuki Fujioka, Wataru Fujii, Makoto Wada, Masataka Kohno, Yutaka Kawahito
Cross-talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1) and thrombin, and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29211678/hemophilia-b-gene-therapy-with-a-high-specific-activity-factor-ix-variant
#17
Lindsey A George, Spencer K Sullivan, Adam Giermasz, John E J Rasko, Benjamin J Samelson-Jones, Jonathan Ducore, Adam Cuker, Lisa M Sullivan, Suvankar Majumdar, Jerome Teitel, Catherine E McGuinn, Margaret V Ragni, Alvin Y Luk, Daniel Hui, J Fraser Wright, Yifeng Chen, Yun Liu, Katie Wachtel, Angela Winters, Stefan Tiefenbacher, Valder R Arruda, Johannes C M van der Loo, Olga Zelenaia, Daniel Takefman, Marcus E Carr, Linda B Couto, Xavier M Anguela, Katherine A High
BACKGROUND: The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia. METHODS: We infused a single-stranded adeno-associated viral (AAV) vector consisting of a bioengineered capsid, liver-specific promoter and factor IX Padua (factor IX-R338L) transgene at a dose of 5×1011 vector genomes per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2% or less of the normal value...
December 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29210752/lactobacillus-casei-beneficially-modulates-immuno-coagulative-response-in-an-endotoxemia-model
#18
Cecilia Haro, María E Mónaco, Marcela Medina
: The current study aims at evaluating the effect of the oral administration of Lactobacillus casei CERELA (CRL) 431 on parameters implicated in inflammation-coagulation interaction using a model of acute inflammation induced by lipopolysaccharide (LPS) in mice. Six-week-old Balb/c mice were treated with L. casei for 5 consecutive days. Then treated and untreated mice received an LPS injection (L. casei + LPS and LPS groups, respectively). Liver and kidney were removed, blood samples were obtained, and hemostatic and inflammatory parameters were evaluated at different times post LPS injection...
November 27, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29209827/hemostasis-endothelial-stress-inflammation-and-the-metabolic-syndrome
#19
REVIEW
Gerald Grandl, Christian Wolfrum
Obesity and the metabolic syndrome (MS) are two of the pressing healthcare problems of our time. The MS is defined as increased abdominal obesity in concert with elevated fasting glucose levels, insulin resistance, elevated blood pressure, and plasma lipids. It is a key risk factor for type 2 diabetes mellitus (T2DM) and for cardiovascular complications and mortality. Here, we review work demonstrating that various aspects of coagulation and hemostasis, as well as vascular reactivity and function, become impaired progressively during chronic ingestion of a western diet, but also acutely after meals...
December 5, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29208927/establishment-of-a-strain-of-haemophilia-a-pigs-by-xenografting-of-foetal-testicular-tissue-from-neonatally-moribund-cloned-pigs
#20
Hiroyuki Kaneko, Kazuhiro Kikuchi, Michiko Nakai, Daiichiro Fuchimoto, Shunichi Suzuki, Shoichiro Sembon, Junko Noguchi, Akira Onishi
Grafting of testicular tissue into immunodeficient mice makes it possible to obtain functional sperm from immature donor animals that cannot be used for reproduction. We have developed a porcine model of human haemophilia A (haemophilia-A pigs) by nuclear transfer cloning from foetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. Despite having a recessive condition, female F8+/- cloned pigs died of severe bleeding at an early age, as was the case for male F8-/Y cloned pigs, thus making it impossible to obtain progeny...
December 5, 2017: Scientific Reports
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