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Coagulation pathways

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https://www.readbyqxmd.com/read/29772364/pathophysiology-and-non-surgical-treatment-of-chronic-subdural-hematoma-from-past-to-present-to-future
#1
REVIEW
Dana C Holl, Victor Volovici, Clemens M F Dirven, Wilco C Peul, Fop van Kooten, Korné Jellema, Niels A van der Gaag, Ishita P Miah, Kuan H Kho, Heleen M den Hertog, Hester F Lingsma, Ruben Dammers
BACKGROUND: Chronic subdural hematoma (CSDH) is one of the more frequent pathological entities in daily neurosurgical practice. Historically, CSDH was considered a progressive, recurrent bleeding with a traumatic etiology. However, recent evidence suggests a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH in order to direct further research questions aiming to optimize treatment for the individual patient...
May 14, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29769259/novel-therapeutics-for-hemophilia-and-other-bleeding-disorders
#2
Michael U Callaghan, Robert Sidonio, Steven W Pipe
Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment for these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase III trial in people with hemophilia A and inhibitors...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29768263/fibrinopeptide-a-induces-expression-of-c-reactive-protein-via-the-ros-erk1-2-p38-nf-%C3%AE%C2%BAb-signal-pathway-in-vascular-smooth-muscle-cells
#3
Shouzhu Xu, Jing Zhao, Juntian Liu, Wei Gou
BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory disease in the artery walls. Fibrinopeptide A (FPA) is a biomarker of the activation of coagulation system, and a high concentration of FPA in blood occurs in patients with ischemic heart disease etc. However, there exist few studies on the pathological effects of FPA in cardiovascular system. Therefore, the present study examined the effect of FPA on CRP expression in VSMCs and the molecular mechanisms. METHODS: mRNA and protein expression was identified by quantitative real-time PCR and Western blot, respectively...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#4
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29746949/variation-in-coagulation-and-fibrinolysis-genes-evaluated-for-their-contribution-to-cerebrovascular-complications-in-adults-with-bacterial-meningitis-in-the-netherlands
#5
A T Kloek, H N Khan, M Valls Seron, A Jongejan, A H Zwinderman, F Baas, A van der Ende, D van de Beek, B Ferwerda, M C Brouwer
OBJECTIVE: To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. METHODS: We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission...
May 7, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29746819/continuous-thrombin-generation-in-whole-blood-new-applications-for-assessing-activators-and-inhibitors-of-coagulation
#6
Shannon M Prior, Kenneth G Mann, Kalev Freeman, Saulius Butenas
Hemostatic tests have been utilized to clarify the blood coagulation potential. The novel thrombin generation (TG) assay of this study provides explicit information and is the most physiologically-relevant hemostatic test ex vivo. We describe how this assay allows for TG under a number of relevant circumstances. First, whole blood (WB) from healthy individuals was analyzed ± 5 pM tissue factor (TF) and ± contact pathway inhibition. Without an exogenous initiator TG was decreased and delayed, but addition of 5 pM TF shortened the lag phase and increased peak thrombin...
May 7, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29745362/does-dietary-nitrate-say-no-to-cardiovascular-ageing-current-evidence-and-implications-for-research
#7
Mario Siervo, Filippo Scialò, Oliver M Shannon, Blossom C M Stephan, Ammar W Ashor
CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic...
May 2018: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/29743514/transcriptomic-integration-of-d-4-r-and-mor-signaling-in-the-rat-caudate-putamen
#8
Alejandra Valderrama-Carvajal, Haritz Irizar, Belén Gago, Haritz Jiménez-Urbieta, Kjell Fuxe, María C Rodríguez-Oroz, David Otaegui, Alicia Rivera
Morphine binding to opioid receptors, mainly to μ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4 R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4 R/MOR interactions...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29741245/pathogenesis-and-diagnosis-of-disseminated-intravascular-coagulation
#9
REVIEW
M Levi
Several clinical conditions, in particular those associated with a systemic inflammatory response, can cause some degree of activation of coagulation but when the procoagulant stimulus is sufficiently severe and overcomes the natural anticoagulant mechanisms of coagulation, disseminated intravascular coagulation (DIC) may occur. The clinical manifestations of DIC encompass multiorgan dysfunction caused by fibrin-platelet clots in the microcirculation, and bleeding caused by consumption of platelets and coagulation factors...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29740591/postnatal-and-adult-aortic-heart-valves-have-distinctive-transcriptional-profiles-associated-with-valve-tissue-growth-and-maintenance-respectively
#10
Emily Nordquist, Stephanie LaHaye, Casey Nagel, Joy Lincoln
Heart valves are organized connective tissues of high mechanical demand. They open and close over 100,000 times a day to preserve unidirectional blood flow by maintaining structure-function relationships throughout life. In affected individuals, structural failure compromises function and often leads to regurgitant blood flow and progressive heart failure. This is most common in degenerative valve disease due to age-related wear and tear, or congenital malformations. At present, the only effective treatment of valve disease is surgical repair or replacement and this is often impermanent and requires anti-coagulation therapy throughout life...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29735342/dabigatran-reduces-endothelial-permeability-through-inhibition-of-thrombin-induced-cytoskeleton-reorganization
#11
Hyun-Jung Choi, Na-Eun Kim, Jayoung Kim, Sunho An, Seung-Hee Yang, Jimin Ha, Sunghee Cho, Il Kwon, Young Dae Kim, Hyo Suk Nam, Ji Hoe Heo
Dabigatran etexilate (DE), a new oral anti-coagulant, is a direct thrombin inhibitor. Clinical trials showed the favorable benefit-to-risk profile of DE compared to warfarin for the prevention of ischemic stroke in patients with atrial fibrillation. Remarkably, patients treated with dabigatran showed reduced rates of intracerebral hemorrhage compared to warfarin. As the breakdown of endothelial barrier integrity is associated with hemorrhagic events and as thrombin increases endothelial permeability, we hypothesized that dabigatran preserves the endothelial barrier by inhibiting thrombin-induced permeability...
April 25, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29731819/cytoprotective-effect-of-aquaporin-1-against-lipopolysaccharide-induced-apoptosis-and-inflammation-of-renal-epithelial-hk-2-cells
#12
Yiduo Wang, Wenzheng Zhang, Guangzhe Yu, Qian Liu, Yingyu Jin
Sepsis is the most common underlying disease of disseminated intravascular coagulation. Acute kidney injury is a common and serious complications of sepsis. In the present study, a lipopolysaccharide (LPS)-induced human proximal tubule cell line (HK-2 cells) was selected as an in vitro model of septic acute kidney injury. The aim of the present study was to investigate whether aquaporin 1 (AQP-1) has a cytoprotective role in LPS-induced HK-2 cells. HK-2 cells were treated with 0-16 µg/ml LPS for 0-24 h to establish the in vitro model of sepsis...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29731736/coagulation-factor-xii-levels-and-intrinsic-thrombin-generation-in-multiple-sclerosis
#13
Nicole Ziliotto, Marcello Baroni, Sofia Straudi, Fabio Manfredini, Rosella Mari, Erica Menegatti, Rebecca Voltan, Paola Secchiero, Paolo Zamboni, Nino Basaglia, Giovanna Marchetti, Francesco Bernardi
Background: Factor XII (FXII) activation initiates the intrinsic (contact) coagulation pathway. It has been recently suggested that FXII could act as an autoimmunity mediator in multiple sclerosis (MS). FXII depositions nearby dentritic cells were detected in the central nervous system of MS patients and increased FXII activity has been reported in plasma of relapsing remitting and secondary progressive MS patients. FXII inhibition has been proposed to treat MS. Objective: To investigate in MS patients multiple FXII-related variables, including the circulating amount of protein, its pro-coagulant function, and their variation over time...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29731655/immune-regulating-effects-of-exercise-on-cigarette-smoke-induced-inflammation
#14
REVIEW
Ashkan Madani, Katharina Alack, Manuel Jonas Richter, Karsten Krüger
Long-term cigarette smoking (LTCS) represents an important risk factor for cardiac infarction and stroke and the central risk factor for the development of a bronchial carcinoma, smoking-associated interstitial lung fibrosis, and chronic obstructive pulmonary disease. The pathophysiologic development of these diseases is suggested to be promoted by chronic and progressive inflammation. Cigarette smoking induces repetitive inflammatory insults followed by a chronic and progressive activation of the immune system...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29731490/sulfasalazine-treatment-can-cause-a-positive-effect-on-lps-induced-endotoxic-rats
#15
Burak Dik, Gonca Sonmez, Hatice Eser Faki, Emre Bahcivan
The aim of this study, was to determine the effect of sulfasalazine for different periods of time reduces disseminated intravascular coagulation, inflammation and organ damages by inhibiting the nuclear factor kappa beta pathway. The study was performed with 30 Wistar albino rats and the groups were established as Control group, LPS group; endotoxemia was induced with LPS, SL5 group: sulfasalazine (300 mg/kg, single dose daily) was administered for 5 days before the LPS-induced endotoxemia, and LS group: sulfasalazine (300 mg/kg, single dose) was administered similtenously with LPS...
May 2, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29728803/acquired-thrombotic-thrombocytopenic-purpura-with-isolated-cfhr3-1-deletion-rapid-remission-following-complement-blockade
#16
Martin Bitzan, Rawan M Hammad, Arnaud Bonnefoy, Watfa Shahwan Al Dhaheri, Catherine Vézina, Georges-Étienne Rivard
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is caused by the abundance of uncleaved ultralarge von Willebrand factor multimers (ULvWF) due to acquired (autoantibody-mediated) or congenital vWF protease ADAMTS13 deficiency. Current treatment recommendations include plasma exchange therapy and immunosuppression for the acquired form and (fresh) frozen plasma for congenital TTP. CASE-DIAGNOSIS/TREATMENT: A previously healthy, 3-year-old boy presented with acute microangiopathic hemolytic anemia, thrombocytopenia, erythrocyturia and mild proteinuria, but normal renal function, and elevated circulating sC5b-9 levels indicating complement activation...
May 4, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29727892/hemostasis-during-extreme-exertion
#17
Cécile Hélène Kicken, Adam Miszta, Hilde Kelchtermans, Bas De Laat
Exercise is protective against cardiovascular disease, but can also provoke sudden cardiac death, a phenomenon referred to as "the exercise paradox." Extreme exertion is known to induce a rebalanced hemostatic state by causing hypercoagulability and concomitantly enhanced fibrinolysis. Over the past decade, novel techniques for quantifying hemostasis have been introduced, which may provide new insights into this process. This review summarizes recent literature on the effect of extreme exertion of both short and long duration on coagulation, fibrinolysis, and recovery of hemostatic balance...
May 4, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29727450/rift-valley-fever-viral-load-correlates-with-the-human-inflammatory-response-and-coagulation-pathway-abnormalities-in-humans-with-hemorrhagic-manifestations
#18
Annabelle de St Maurice, Jessica Harmon, Luke Nyakarahuka, Stephen Balinandi, Alex Tumusiime, Jackson Kyondo, Sophia Mulei, Annemarion Namutebi, Barbara Knust, Trevor Shoemaker, Stuart T Nichol, Anita K McElroy, Christina F Spiropoulou
Rift Valley fever virus is an arbovirus that affects both livestock and humans throughout Africa and in the Middle East. Despite its endemicity throughout Africa, it is a rare event to identify an infected individual during the acute phase of the disease and an even rarer event to collect serial blood samples from the affected patient. Severely affected patients can present with hemorrhagic manifestations of disease. In this study we identified three Ugandan men with RVFV disease that was accompanied by hemorrhagic manifestations...
May 4, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29727017/recent-advances-in-the-discovery-and-development-of-factor-xi-xia-inhibitors
#19
REVIEW
Rami A Al-Horani, Daniel K Afosah
Factor XIa (FXIa) is a serine protease homodimer that belongs to the intrinsic coagulation pathway. FXIa primarily catalyzes factor IX activation to factor IXa, which subsequently activates factor X to factor Xa in the common coagulation pathway. Growing evidence suggests that FXIa plays an important role in thrombosis with a relatively limited contribution to hemostasis. Therefore, inhibitors targeting factor XI (FXI)/FXIa system have emerged as a paradigm-shifting strategy so as to develop a new generation of anticoagulants to effectively prevent and/or treat thromboembolic diseases without the life-threatening risk of internal bleeding...
May 4, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29723281/immunity-to-lulohya-and-lundep-the-salivary-spreading-factors-from-lutzomyia-longipalpis-protects-against-leishmania-major-infection
#20
Ines Martin-Martin, Andrezza Campos Chagas, Anderson B Guimaraes-Costa, Laura Amo, Fabiano Oliveira, Ian N Moore, Thiago S DeSouza-Vieira, Elda E Sanchez, Montamas Suntravat, Jesus G Valenzuela, Jose M C Ribeiro, Eric Calvo
Salivary components from disease vectors help arthropods to acquire blood and have been shown to enhance pathogen transmission in different model systems. Here we show that two salivary enzymes from Lutzomyia longipalpis have a synergist effect that facilitates a more efficient blood meal intake and diffusion of other sialome components. We have previously shown that Lundep, a highly active endonuclease, enhances parasite infection and prevent blood clotting by inhibiting the intrinsic pathway of coagulation...
May 3, 2018: PLoS Pathogens
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