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Tissue factor, coagulation

S He, M Blombäck, F Boström, H Wallen, J Svensson, A Östlund
Acute traumatic coagulopathy (ATC) diagnosed by prolongation of APTT and/or PT/INR involves alterations in platelet activity, coagulation and fibrinolysis. However, data showing the haemostatic situation in injured patients without ATC are scarce. To assess whether haemostatic impairment is also present in injured patients without ATC, ten injured patients without ATC and ten normal individuals were examined. The patients were sampled on arrival at the emergency department 0, 2, 12 h after surgical or other intervention...
March 21, 2018: Journal of Thrombosis and Thrombolysis
David A Slatter, Charles L Percy, Keith Allen-Redpath, Joshua M Gajsiewicz, Nick J Brooks, Aled Clayton, Victoria J Tyrrell, Marcela Rosas, Sarah N Lauder, Andrew Watson, Maria Dul, Yoel Garcia-Diaz, Maceler Aldrovandi, Meike Heurich, Judith Hall, James H Morrissey, Sebastien Lacroix-Desmazes, Sandrine Delignat, P Vincent Jenkins, Peter W Collins, Valerie B O'Donnell
Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell-derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB)...
March 22, 2018: JCI Insight
Priyadarsini Kumar, Kewa Gao, Chuwang Wang, Christopher Pivetti, Lee Lankford, Diana Farmer, Aijun Wang
Hemophilia A (HA) is an X-linked recessive disorder caused by mutations in the factor VIII ( FVIII) gene leading to deficient blood coagulation. The current standard of care is frequent infusions of plasma-derived FVIII or recombinant B-domain-deleted FVIII (BDD-FVIII). While this treatment is effective, many patients eventually develop FVIII inhibitors that limit the effectiveness of the infused FVIII. As a monogenic disorder, HA is an ideal target for gene or cell-based therapy. Several studies have investigated allogeneic stem cell therapy targeting in utero or postnatal treatment of HA but have not been successful in completely correcting HA...
January 2018: Cell Transplantation
Qiong Wang, Wei Huang, Hong-Yang Wu
OBJECTIVE: To observe the effect of acupuncture on the expression of silent information regulator factor 2-related enzyme 1 (SIRT 1) and nuclear factor-κB (NF-κB) in rats with acute cerebral ischemia (ACI), so as to explore its mechanisms underlying improvement of ACI. METHODS: One hundred female SD rats were randomly divided into 5 groups: normal control (normal), sham-operation (sham), model, non-acupoint and acupoint, with 20 rats in each. The ACI model was established by occlusion (electric coagulation) of the middle cerebral artery after craniotomy...
March 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ying Su, Jingli Chen, Zengxiang Dong, Yan Zhang, Ruishuang Ma, Junjie Kou, Feng Wang, Jialan Shi
BACKGROUND/AIMS: The mechanisms for thrombosis in diabetic retinopathy (DR) are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS) exposure on microparticles (MPs) and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA) in DR patients. METHODS: PS-positive MPs and cells from healthy controls (n = 20) and diabetic patients (n = 60) were analyzed by flow cytometry and confocal microscopy...
March 15, 2018: Cellular Physiology and Biochemistry
Anirban Banerjee, Christopher C Silliman, Ernest E Moore, Monika Dzieciatskowa, Marguerite Kelher, Angela Sauaia, Kenneth Jones, Michael P Chapman, Eduardo Gonzalez, Hunter B Moore, Angelo D'Alessandro, Erik Peltz, Benjamin E Huebner, Peter Einerson, James Chandler, Arsen Ghasabayan, Kirk Hansen
BACKGROUND: Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. METHODS: Blood samples were collected in the field or at Emergency Department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Guang Shi, Jun-Wei Zhao, Xiao-Xu Sun, Jun-Fen Ma, Pan Wang, Fu-Cheng He, Liang Ming
The interaction between inflammatory processes and a hypercoagulant state may aggravate the severity of asthma and stimulate the airway remodeling of asthma. The aim of the current study was to evaluate the association between the negative inflammatory regulator tumor necrosis factor α induced protein-8 like-2 (TIPE2) and the coagulating substances tissue factor (TF) and thrombospondin-1 (TSP-1) in patients with bronchial asthma. Compared with healthy controls, TIPE2 expression was significantly downregulated, whereas TF expression was upregulated in the peripheral blood mononuclear cells (PBMCs) of patients with bronchial asthma...
April 2018: Experimental and Therapeutic Medicine
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
Cecilia Augustsson, Anders Svensson, Birgitte Kjaer, Tzu-Yuan Chao, Xia Wenjuan, Berit Olsen Krogh, Jens Breinholt, Jes Thorn Clausen, Ida Hilden, Helle Heibroch Petersen, Lars Christian Petersen
BACKGROUND: Initiation of coagulation is induced by binding of activated factor VII (FVIIa) to tissue factor (TF) and activation of factor X (FX) in a process regulated by tissue factor pathway inhibitor (TFPI). TFPI contains three Kunitz-type protease inhibitor domains (K1-K3) of which K1 and K2 block the active sites of FVIIa and FXa respectively. OBJECTIVE: To produce a monoclonal antibody (mAb) directed towards K1, to characterize the binding epitope, and to study its effect on TFPI inhibition...
March 12, 2018: Journal of Thrombosis and Haemostasis: JTH
Awen Menou, JanWillem Duitman, Bruno Crestani
Idiopathic Pulmonary Fibrosis (IPF) is a devastating chronic, progressive and irreversible disease that remains refractory to current therapies. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the development of pulmonary fibrosis since decades. Coagulation signalling deregulation, which influences several key inflammatory and fibro-proliferative responses, is also essential in IPF pathogenesis, and a growing body of evidence indicates that Protease-Activated Receptors (PARs) inhibition in IPF may be promising for future evaluation...
March 5, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Michaela Oeller, Sandra Laner-Plamberger, Sarah Hochmann, Nina Ketterl, Martina Feichtner, Gabriele Brachtl, Anna Hochreiter, Cornelia Scharler, Lara Bieler, Pasquale Romanelli, Sebastien Couillard-Despres, Elisabeth Russe, Katharina Schallmoser, Dirk Strunk
Intravascular transplantation of tissue factor (TF)-bearing cells elicits an instant blood-mediated inflammatory reaction (IBMIR) resulting in thrombotic complications and reduced engraftment. Here we studied the hemocompatibility of commonly used human white adipose tissue (WAT), umbilical cord (UC) and bone marrow stromal cells (BMSC) and devised a possible strategy for safe and efficient stromal cell transplantation. Methods: Stromal cell identity, purity, and TF expression was tested by RTQ-PCR, flow cytometry and immunohistochemistry...
2018: Theranostics
Sumanth Kumbargere Nagraj, Eachempati Prashanti, Himanshi Aggarwal, Ashok Lingappa, Murugan S Muthu, Salian Kiran Kumar Krishanappa, Haszelini Hassan
BACKGROUND: Post-extraction bleeding (PEB) is a recognised, frequently encountered complication in dental practice, which is defined as bleeding that continues beyond 8 to 12 hours after dental extraction. The incidence of post-extraction bleeding varies from 0% to 26%. If post-extraction bleeding is not managed, complications can range from soft tissue haematomas to severe blood loss. Local causes of bleeding include soft tissue and bone bleeding. Systemic causes include platelet problems, coagulation disorders or excessive fibrinolysis, and inherited or acquired problems (medication induced)...
March 4, 2018: Cochrane Database of Systematic Reviews
Praveen Papareddy, Gopinath Kasetty, Saud Alyafei, Emanuel Smeds, Outi M H Salo-Ahen, Stefan R Hansson, Arne Egesten, Heiko Herwald
Coagulation, complement, and innate immunity are tightly interwoven and form an alliance that can be traced back to early eukaryotic evolution. Here we employed an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1-derived peptides from the different classes of vertebrates (i.e. fish, reptile, bird, and mammals) and tested whether they can boost killing of various human bacterial pathogens in plasma. We found signs of species-specific conservation and diversification during evolution in these peptides that significantly impact their antibacterial activity...
February 23, 2018: Virulence
Marcus Lehmann, Rogier M Schoeman, Patrick J Krohl, Alison M Wallbank, Joseph R Samaniuk, Martine Jandrot-Perrus, Keith B Neeves
OBJECTIVE: The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. APPROACH AND RESULTS: A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Marta Brambilla, Paolo Gelosa, Laura Rossetti, Laura Castiglioni, Chiara Zara, Paola Canzano, Elena Tremoli, Luigi Sironi, Marina Camera
OBJECTIVE: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression...
March 6, 2018: Journal of Hypertension
Brice Oulion, James S Dobson, Christina N Zdenek, Kevin Arbuckle, Callum Lister, Francisco C P Coimbra, Bianca Op den Brouw, Jordan Debono, Aymeric Rogalski, Aude Violette, Rudy Fourmy, Nathaniel Frank, Bryan G Fry
Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Bite reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated...
February 17, 2018: Toxicology Letters
Stella Thomassen, Tom G Mastenbroek, Frauke Swieringa, Kristien Winckers, Marion A H Feijge, Roy Schrijver, Judith M E M Cosemans, Susan A Maroney, Alan E Mast, Tilman M Hackeng, Johan W M Heemskerk
Tissue factor pathway inhibitor-alpha (TFPI-α) is a Kunitz-type serine protease inhibitor, which suppresses coagulation by inhibiting the tissue factor (TF)/factor VIIa complex as well as factor Xa. In static plasma-phospholipid systems, TFPI-α thus suppresses both factor Xa and thrombin generation. In this article, we used a microfluidics approach to investigate how TFPI-α regulates fibrin clot formation in platelet thrombi at low wall shear rate. We therefore hypothesized that the anticoagulant effect of TFPI-α in plasma is a function of the local procoagulant strength-defined as the magnitude of thrombin generation under flow, due to local activities of TF/factor VIIa and factor Xa...
February 16, 2018: Thrombosis and Haemostasis
Hong Liu, Wei-Wei Su, Chao-Feng Long, Wei-Jian Zhang, Pei-Bo Li, Zhong Wu, Yin-Yin Liao, Xuan Zeng, Tao-Bin Chen, Yu-Ying Zheng, Zeng-Hao Yan, Cong Bi, Hong-Liang Yao
Currently, the prevention and treatment of hypertensive crises especially when it occurs with serious adverse outcomes have led to worldwide controversy. Despite of clinical possibilities of multiple agents, clinical failures still occur frequently. Therefore, early evaluations and observations of different therapies on appropriate animals should be emphasized. In the present study, an animal model for hypertensive crises emergencies was firstly established and experimentally testified. Five-month-male spontaneously hypertensive rat was consecutively fed with 60%-Kcal fat diet for four, six, and eight weeks with body weight and blood pressure monitored every two weeks, and then followed by an acute vasoconstriction stress of 5-min ice-bath treatment in the 4-h time interval of two adrenaline injections (0...
January 1, 2018: Experimental Biology and Medicine
Daniel S Gaul, Julien Weber, Lambertus J Van Tits, Susanna Sluka, Lisa Pasterk, Martin F Reiner, Natacha Calatayud, Christine Lohmann, Roland Klingenberg, Jürgen Pahla, Daria Vdovenko, Felix C Tanner, Giovanni G Camici, Urs Eriksson, Johan Auwerx, François Mach, Stephan Windecker, Nicolas Rodondi, Thomas F L Uuml Scher, Stephan Winnik, Christian M Matter
BACKGROUND: Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3-/- mice (n = 6) was reduced by half compared to Sirt3+/+ wildtype (WT, n = 8, p<0...
February 10, 2018: Cardiovascular Research
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