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Clotting cascade

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https://www.readbyqxmd.com/read/28414674/a-clot-possibly-due-to-loss-of-tnf-%C3%AE-supression
#1
J Broussard, M Berlinger, D Lauret
INTRODUCTION: Inflammation and venous thrombosis enjoy a close Relationship. We present a patient who had multiple DVTs following the discontinuation of anti- TNF-α therapy. CASE: A 34 year old African American female with a history of multiple DVT's, miscarriages, and reported Crohn's disease presented with shortness of breath. In the Emergency Department, CTA showed bilateral pulmonary emboli. The patient had been off adalimumab for one year and reported abdominal pain with 6-7 non-bloody bowel movements daily...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28405673/gly74ser-mutation-in-protein-c-causes-thrombosis-due-to-a-defect-in-protein-s-dependent-anticoagulant-function
#2
Changming Chen, Likui Yang, Bruno O Villoutreix, Xuefeng Wang, Qiulan Ding, Alireza R Rezaie
Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation by thrombin in complex with thrombomodulin (TM) down-regulates the clotting cascade by a feedback loop inhibition mechanism. Activated protein C (APC) exerts its anticoagulant function through protein S-dependent degradation of factors Va and VIIIa. We recently identified a venous thrombosis patient whose plasma level of protein C antigen is normal, but its anticoagulant activity is only 34 % of the normal level. Genetic analysis revealed that the proband and her younger brother carry a novel heterozygous mutation c...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28347652/reaction-diffusion-waves-of-blood-coagulation
#3
Tatiana Galochkina, Anass Bouchnita, Polina Kurbatova, Vitaly Volpert
One of the main characteristics of blood coagulation is the speed of clot growth. In the current work we consider a mathematical model of the coagulation cascade and study existence, stability and speed of propagation of the reaction-diffusion waves of blood coagulation. We also develop a simplified one-equation model that reflects the main features of the thrombin wave propagation. For this equation we estimate the wave speed analytically. The resulting formulas provide a good approximation for the speed of wave propagation in a more complex model as well as for the experimental data...
March 24, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#4
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28270519/plasminogen-activator-inhibitor-1-regulates-macrophage-dependent-postoperative-adhesion-by-enhancing-egf-her1-signaling-in-mice
#5
Kumpei Honjo, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Hiroshi Shimazu, Salita Eiamboonsert, Douaa Dhahri, Atsuhiko Ichimura, Takashi Dan, Toshio Miyata, Kazuyoshi Takeda, Kazuhiro Sakamoto, Koichi Hattori, Beate Heissig
Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat(-/-) and Serpine1(-/-) In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275...
March 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28248073/carbon-nanotubes-activate-limulus-amebocyte-lysate-coagulation-by-interface-adsorption
#6
Man Yang, Xin Nie, Jie Meng, Jian Liu, Zhiwei Sun, Haiyan Xu
Limulus amebocyte lysate (LAL) assay is worldwide requested in the assessment of endotoxin contamination for biomaterials. As carbon nanotubes are one major nanomaterial with multiple potentials in biomedical application, here we investigate whether oxidized multiwalled carbon nanotubes (O-MWCNT) interferes the assessment by LAL assays. We showed that the endotoxin free O-MWCNT dispersing in aqueous solutions could activate both the gel-clotting and the end-point chromogenic LAL assay by converting coagulogen into coagulin through interfacial interactions between O-MWCNT and enzymes in the assays...
March 3, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28236427/procoagulant-extracellular-vesicles-in-amniotic-fluid
#7
Lena Hell, Lukas Wisgrill, Cihan Ay, Andreas Spittler, Michael Schwameis, Bernd Jilma, Ingrid Pabinger, Peter Altevogt, Johannes Thaler
Embolization of amniotic fluid (AF) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (TF)-exposing extracellular vesicles (EVs) might play an important role in AF embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of AF with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated TF activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in AF and control plasma...
February 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28225379/the-presentation-of-a-fussy-infant-with-bruising-late-onset-vitamin-k-deficiency-bleeding
#8
Katherine Wolpert, Matthew Szadkowski, Michael Miescier, Hilary A Hewes
Vitamin K plays an integral role in the clotting cascade. Deficiency, specifically in vulnerable neonates with insufficient stores, can lead to spontaneous bleeding and devastating effects. In this case, we report a young infant with late-onset vitamin K deficiency bleeding who did not receive vitamin K prophylaxis after birth. Initially presenting with bruising and fussiness, the patient was later found to have intracerebral hemorrhage with midline shift and uncal herniation. The infant was not a surgical candidate and died shortly thereafter...
February 21, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28223350/mapping-atheroprotective-functions-and-related-proteins-lipoproteins-in-size-fractionated-human-plasma
#9
Debi K Swertfeger, Hailong Li, Sandra Rebholz, Xiaoting Zhu, Amy S Shah, W Sean Davidson, Long J Lu
HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS)...
April 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223279/distinct-contributions-of-complement-factors-to-platelet-activation-and-fibrin-formation-in-venous-thrombus-development
#10
Saravanan Subramaniam, Kerstin Jurk, Lukas Hobohm, Sven Jäckel, Mona Saffarzadeh, Kathrin Schwierczek, Philip Wenzel, Florian Langer, Christoph Reinhardt, Wolfram Ruf
Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity and the coagulation and complement cascades. Here we show in a tissue factor (TF)-dependent model of flow restriction-induced venous thrombosis that complement factors (C) make distinct contributions to platelet activation and fibrin deposition. C3-deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28213103/expression-and-characterization-of-haemathrins-madanin-like-thrombin-inhibitors-isolated-from-the-salivary-gland-of-tick-haemaphysalis-bispinosa-acari-ixodidae
#11
Rajeev Kungur Brahma, Guillaume Blanchet, Simran Kaur, R Manjunatha Kini, Robin Doley
Saliva of hematophagous animals, such as ticks, is an excellent source of anticoagulant proteins and polypeptides. Here we describe the identification and characterization of two thrombin inhibitors named as haemathrin 1 and 2 from the salivary gland of tick Haemaphysalis bispinosa using genomic approach. Haemathrins are cysteine-less peptide anticoagulants, which share about 65-70% identity with madanins, and belong to inhibitor I53 superfamily of inhibitors of the MEROPS database. Haemathrins were overexpressed in E...
January 31, 2017: Thrombosis Research
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
#12
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/28120727/antiplatelet-agents-and-anticoagulants-from-pharmacology-to-clinical-practice
#13
Maria E Tsoumani, Alexandros D Tselepis
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28089408/the-various-assays-for-measuring-activity-states-of-factor-viia-in-plasma-and-therapeutic-products-diagnostic-value-and-analytical-usefulness-in-various-pathophysiological-states
#14
REVIEW
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms...
February 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28079789/the-impact-of-irrigating-fluid-absorption-on-blood-coagulation-in-patients-undergoing-transurethral-resection-of-the-prostate-a-prospective-observational-study-using-rotational-thromboelastometry
#15
Hyun-Jung Shin, Hyo-Seok Na, Young-Tae Jeon, Hee-Pyoung Park, Sun-Woo Nam, Jung-Won Hwang
Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28035951/a-systematic-review-of-the-role-of-dysfunctional-wound-healing-in-the-pathogenesis-and-treatment-of-idiopathic-pulmonary-fibrosis
#16
REVIEW
Alan Betensley, Rabab Sharif, Dimitrios Karamichos
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments...
December 26, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28007958/polyphosphate-and-rna-differentially-modulate-the-contact-pathway-of-blood-clotting
#17
Joshua M Gajsiewicz, Stephanie A Smith, James H Morrissey
The contact pathway of the plasma clotting cascade is dispensable for normal hemostasis, but contributes to thrombosis and serves as a bridge between inflammation and coagulation. This pathway is triggered upon exposure of plasma to certain anionic polymers and artificial surfaces. Recently, extracellular nucleic acids and inorganic polyphosphate (polyP) have been implicated as being important (patho)physiologically relevant activators of this pathway. However, mechanistic details regarding how nucleic acids or polyP modulate the individual reactions of the contact pathway have been lacking...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28005926/the-central-role-of-kng1-gene-as-a-genetic-determinant-of-coagulation-pathway-related-traits-exploring-metaphenotypes
#18
Helena Brunel, Raimon Massanet, Angel Martinez-Perez, Andrey Ziyatdinov, Laura Martin-Fernandez, Juan Carlos Souto, Alexandre Perera, José Manuel Soria
Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i...
2016: PloS One
https://www.readbyqxmd.com/read/27994741/discovery-of-phenylglycine-lactams-as-potent-neutral-factor-viia-inhibitors
#19
Nicholas R Wurtz, Brandon L Parkhurst, Wen Jiang, Indawati DeLucca, Xiaojun Zhang, Vladimir Ladziata, Daniel L Cheney, Jeffrey R Bozarth, Alan R Rendina, Anzhi Wei, Joseph M Luettgen, Yiming Wu, Pancras C Wong, Dietmar A Seiffert, Ruth R Wexler, E Scott Priestley
Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27942785/-factor%C3%A2-xiii-pharmacodynamic-and-pharmacokinetic-characteristics
#20
REVIEW
E H Adam, S Kreuer, K Zacharowski, C F Weber, R Wildenauer
Factor XIII (FXIII) plays an important role in the field of blood coagulation. In the last decade, both congenital and acquired deficiencies have been investigated in clinical studies. FXIII is a versatile enzyme that leads to a covalent cross-linking of fibrin fibrils at the end of the clotting cascade and supports platelet adhesion to the damaged sub-endothelium with the result of a mechanically stable clot.Symptoms of FXIII deficiencies vary within a broad spectrum from superficial skin bleeding episodes to severe, sometimes life threatening hemorrhage, requiring prophylactic or therapeutic replacement therapy...
January 2017: Der Anaesthesist
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