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Sepsis and coagulation

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https://www.readbyqxmd.com/read/28092405/thrombin-contributes-to-protective-immunity-in-pneumonia-derived-sepsis-via-fibrin-polymerization-and-platelet-neutrophil-interactions
#1
Theodora A M Claushuis, Sacha F de Stoppelaar, Ingrid Stroo, Joris J T H Roelofs, Roelof Ottenhoff, Tom van der Poll, Cornelis van 't Veer
BACKGROUND: Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental for outcome due to microvascular failure but can also enhance host defense. The role of thrombin herein has not been fully elucidated. OBJECTIVE: We aimed to investigate the contribution of thrombin to the host response during pneumonia derived sepsis. METHODS: Mice treated with the specific thrombin inhibitor Dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K...
January 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28079606/relationship-between-alternative-resuscitation-strategies-host-response-and-injury-biomarkers-and-outcome-in-septic-shock-analysis-of-the-protocol-based-care-for-early-septic-shock-study
#2
John A Kellum, Francis Pike, Donald M Yealy, David T Huang, Nathan I Shapiro, Derek C Angus
OBJECTIVES: The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. DESIGN: Secondary analysis of a large randomized clinical trial...
January 10, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28079604/prior-use-of-calcium-channel-blockers-is-associated-with-decreased-mortality-in-critically-ill-patients-with-sepsis-a-prospective-observational-study
#3
Maryse A Wiewel, Lonneke A van Vught, Brendon P Scicluna, Arie J Hoogendijk, Jos F Frencken, Aeilko H Zwinderman, Janneke Horn, Olaf L Cremer, Marc J Bonten, Marcus J Schultz, Tom van der Poll
OBJECTIVES: Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis. DESIGN: A prospective observational study. SETTING: The ICUs of two tertiary care hospitals in the Netherlands. PATIENTS: In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18...
January 10, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28078348/the-fifth-epidermal-growth-factor-like-region-of-thrombomodulin-alleviates-lps-induced-sepsis-through-interacting-with-g-protein-coupled-receptor-15
#4
Bin Pan, Xiangmin Wang, Shinsuke Kojima, Chie Nishioka, Akihito Yokoyama, Goichi Honda, Kailin Xu, Takayuki Ikezoe
Thrombomodulin (TM) exerts cytoprotection via the fifth region of epidermal growth factor (EGF)-like domain of TM (TME5) by interacting with G-protein coupled receptor 15 (GPR15) expressed on cell surface of vascular endothelial cells. TM is also implied to mediate anti-inflammatory functions by unknown mechanism. By applying a lipopolysaccharide (LPS)-induced murine sepsis model, we assessed the role of TME5 in septic inflammation and coagulation. We found that TME5 treatment protected mice in association with ameliorating inflammation and coagulopathy in LPS-induced sepsis...
January 12, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28073784/platelets-and-neutrophil-extracellular-traps-collaborate-to-promote-intravascular-coagulation-during-sepsis-in-mice
#5
Braedon McDonald, Rachelle P Davis, Seok-Joo Kim, Mandy Tse, Charles T Esmon, Elzbieta Kolaczkowska, Craig N Jenne
Neutrophil extracellular traps (NETs; webs of DNA coated in anti-microbial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multi-color confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28043040/rho-kinase-inhibitor-treatment-prevents-pulmonary-inflammation-and-coagulation-in-lipopolysaccharide-induced-lung-injury
#6
Renyu Ding, Dongmei Zhao, Xiaoxia Li, Baoyan Liu, Xiaochun Ma
INTRODUCTION: In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced acute lung injury (ALI) models. METHODS: In the in vivo study, mice were randomized to four different groups: Control, Y-27632 (Y), LPS, and LPS+Y-27632 (LPS+Y)...
December 24, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28029716/inactivation-of-human-coagulation-factor-x-by-a-protease-of-the-pathogen-capnocytophaga-canimorsus
#7
K Hack, F Renzi, E Hess, F Lauber, J Douxfils, J M Dogné, G R Cornelis
BACKGROUND: Capnocytophaga canimorsus is a Gram-negative bacterium, which belongs to the oral flora of dogs and causes fulminant sepsis in humans who have been bitten, licked or scratched. In patients, bleeding abnormalities, such as petechiae, purpura fulminans or disseminated intravascular coagulation (DIC) occur frequently. OBJECTIVE: We investigated whether C. canimorsus could actively contribute to these bleeding abnormalities. METHODS: Calibrated automated thrombogram and clotting time assays were performed to assess the anticoagulant activity of C...
December 28, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28024455/the-neisseria-meningitidis-lpxl1-mutant-induces-less-tissue-factor-expression-and-activity-in-primary-human-monocytes-and-monocyte-derived-microvesicles-than-the-wild-type-meningococcus
#8
Marit Hellum, Anne-Marie S Trøseid, Jens P Berg, Petter Brandtzaeg, Reidun Øvstebø, Carola E Henriksson
Neisseria meningitidis (N. meningitidis) may cause sepsis and meningitis. N. meningitidis with a mutated lpxL1 gene has five, instead of six, acyl chains in the lipid A moiety. Compared with patients infected with the wild type (wt) meningococcus, patients infected with the lpxL1 mutant have a mild meningococcal disease with less systemic inflammation and less coagulopathy. Circulating tissue factor (TF), the main initiator of coagulation, has a central role in the development of coagulation disturbances during sepsis...
January 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27997925/immunothrombosis-in-acute-respiratory-distress-syndrome-cross-talks-between-inflammation-and-coagulation
#9
Frantzeska Frantzeskaki, Apostolos Armaganidis, Stylianos E Orfanos
Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation impairment. The syndrome is most commonly a manifestation of sepsis-induced organ dysfunction, characterized by disruption of endothelial barrier integrity and diffuse lung damage. Imbalance between coagulation and inflammation is a predominant characteristic of ARDS, leading to extreme inflammatory response and diffuse fibrin deposition in vascular capillary bed and alveoli...
December 21, 2016: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/27993201/antithrombin-iii-improved-neutrophil-extracellular-traps-in-lung-after-the-onset%C3%A2-of%C3%A2-endotoxemia
#10
Michiko Ishikawa, Hayato Yamashita, Nobuki Oka, Takahiro Ueda, Keisuke Kohama, Atsunori Nakao, Joji Kotani
BACKGROUND: Coagulation and inflammation are closely linked during acute inflammatory conditions, such as sepsis. Antithrombin (AT) is an anticoagulant that also has anti-inflammatory activities. The effects of therapeutically administering AT III after the onset of endotoxemia or sepsis were not clear. Here, we studied the effects of administering AT III after inducing lethal endotoxemia in mice. METHODS: Mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce endotoxemia...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27989251/priapism-as-the-presenting-complaint-in-fatal-group-a-streptococcal-induced-disseminated-intravascular-coagulation
#11
Richard J Baverstock, Colleen Carey
A 60-year-old male presented to an emergency department (ED) with priapism following a sore throat illness. He did not have typical findings of sepsis. The patient then developed severe headache, mental status changes, and hypertension, then suffered a cardiopulmonary arrest. Autopsy showed group A streptococcal (GAS) sepsis, disseminated intravascular coagulation (DIC), and a septic thrombosis to the penile vein. This is the first known case of priapism being the presenting symptom of DIC.
December 19, 2016: CJEM
https://www.readbyqxmd.com/read/27978589/gene-variations-in-the-protein-c-and-fibrinolytic-pathway-relevance-for-severity-and-outcome-in-pediatric-sepsis
#12
Navin P Boeddha, Marieke Emonts, Marjon H Cnossen, Moniek P de Maat, Frank W Leebeek, Gertjan J Driessen, Jan A Hazelzet
The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis...
December 15, 2016: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/27977318/nebulized-recombinant-human-tissue-factor-pathway-inhibitor-attenuates-coagulation-and-exerts-modest-anti-inflammatory-effects-in-rat-models-of-lung-injury
#13
Florry E van den Boogaard, Jorrit J Hofstra, Xanthe Brands, Marcel M Levi, Joris J T H Roelofs, Sebastiaan A J Zaat, Cornelis Van't Veer, Tom van der Poll, Marcus J Schultz
BACKGROUND: Critically ill patients are at a constant risk of direct (e.g., by pneumonia) or indirect lung injury (e.g., by sepsis). Excessive alveolar fibrin deposition is a prominent feature of lung injury, undermining pulmonary integrity and function. METHODS: We examined the effect of local administration of recombinant human tissue factor pathway inhibitor (rh-TFPI), a natural anticoagulant, in two well-established models of lung injury in rats. Rats received intratracheal instillation of Pseudomonas aeruginosa, causing direct lung injury, or they received an intravenous injection of Escherichia coli lipopolysaccharide (LPS), causing indirect lung injury...
December 15, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/27941592/pathological-role-and-diagnostic-value-of-endogenous-host-defense-peptides-in-adult-and-neonatal-sepsis-a-systematic-review
#14
Jeffery Ho, Lin Zhang, Xiaodong Liu, Sunny H Wong, Maggie H T Wang, Benson W M Lau, Shirley P C Ngai, Hung Chan, Gordon Choi, Czarina C H Leung, Wai T Wong, Sharon Tsang, Tony Gin, Jun Yu, Matthew T V Chan, William K K Wu
BACKGROUND: Sepsis is a systemic host response to an infection leading to organ failure. This is associated with dynamic expression of endogenous host defense peptides. Dysregulation of these peptides is associated with septic morbidity and mortality. METHODS: We performed a systematic search of articles indexed in Pubmed, ISI Web of Knowledge, EmBase and Scopus database from inception to October 2016. Both preclinical and clinical studies investigating the role of host defense peptides in pathogenesis and as biomarkers for sepsis were included...
December 9, 2016: Shock
https://www.readbyqxmd.com/read/27939130/the-natural-history-of-pneumonic-tularemia-in-female-fischer-344-rats-after-inhalational-exposure-to-aerosolized-francisella-tularensis-subspecies-tularensis-strain-schu-s4
#15
Julie A Hutt, Julie A Lovchik, Alexander Dekonenko, Andrew C Hahn, Terry H Wu
The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4...
December 8, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27927771/propagation-of-thrombosis-by-neutrophils-and-extracellular-nucleosome-networks
#16
Susanne Pfeiler, Konstantin Stark, Steffen Massberg, Bernd Engelmann
Neutrophils, early mediators of innate immune defense, are recruited to developing thrombi in different types of thrombosis. They amplify intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation. Neutrophil-dependent prothrombotic mechanisms are supported by the externalization of decondensed nucleosomes and granule proteins that together form neutrophil extracellular traps...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27922551/sphingosine-1-phosphate-s1p-a-potential-biomarker-and-therapeutic-target-for-endothelial-dysfunction-and-sepsis
#17
Martin S Winkler, Axel Nierhaus, Annika Poppe, Gillis Greiwe, Markus Gräler, Guenter Daum
Sepsis is an acute life-threatening multiple organ failure caused by a dysregulated host response to infection. Endothelial dysfunction, particularly barrier disruption leading to increased vascular permeability, edema and insufficient tissue oxygenation is critical to sepsis pathogenesis. Sphingosine-1-phosphate (S1P) is a signaling lipid that regulates important pathophysiological processes including vascular endothelial cell permeability, inflammation and coagulation. It is present at high concentrations in blood and lymph and at very low concentrations in tissues due to the activity of the S1P-degrading enzyme S1P-lyase in tissue cells...
December 2, 2016: Shock
https://www.readbyqxmd.com/read/27899386/thyroid-abscess-in-case-of-pre-b-acute-lymphoblastic-leukaemia-a-rare-presentation
#18
Siddhesh Arun Kalantri, Saikat Datta, Dhritiman Maitra, Maitreyee Bhattacharyya
Thyroid abscess is a very rare clinical condition. It usually occurs in immunocompromised individuals or those with underlying malignancy. We report a case of multiple thyroid abscesses in the patient with Pre B acute lymphoblastic leukaemia which developed secondary to hematogenous spread from pyomyositis of right calf muscle. The patient developed sepsis-associated disseminated intravascular coagulation, which got resolved after thyroidectomy. He became afebrile after surgical intervention. Unfortunately, all the cultures were negative...
November 29, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27886531/coagulation-and-sepsis
#19
REVIEW
Marcel Levi, Tom van der Poll
Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail...
January 2017: Thrombosis Research
https://www.readbyqxmd.com/read/27881097/ischaemic-stroke-and-clostridium-septicum-sepsis-and-meningitis-in-a-patient-with-occult-colon-carcinoma-a-case-report-and-review-of-the-literature
#20
Kosmas Macha, Antje Giede-Jeppe, Hannes Lücking, Roland Coras, Hagen B Huttner, Jürgen Held
BACKGROUND: Clostridium septicum is a rare cause of meningitis and brain abscess in children and adults. Gas production by the pathogen can lead to pneumocephalus and the overall mortality rate of Clostridium septicum CNS infection is as high as 74%. The most common entry site of the pathogen is the gastrointestinal tract. CASE PRESENTATION: We describe a 74-year-old man who presented with a left-sided cerebral infarction in the middle cerebral artery territory...
November 24, 2016: BMC Neurology
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