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https://www.readbyqxmd.com/read/29343993/management-of-disseminated-intravascular-coagulation-current-insights-on-antithrombin-and-thrombomodulin-treatments
#1
REVIEW
Mineji Hayakawa
Sepsis and septic shock are frequently complicated by disseminated intravascular coagulation (DIC), which decreases the survival rate of patients with sepsis. In the past, large international randomized controlled trials (RCTs) using physiological anticoagulants for sepsis-induced DIC were not performed; however, RCTs have been conducted for sepsis and/or septic shock. In these trials, physiological anticoagulants did not show any beneficial effects compared with placebo for the treatment of sepsis and/or septic shock...
2018: Open Access Emergency Medicine: OAEM
https://www.readbyqxmd.com/read/29337920/acute-traumatic-endotheliopathy-in-isolated-severe-brain-injury-and-its-impact-on-clinical-outcome
#2
Venencia Albert, Arulselvi Subramanian, Deepak Agrawal, Hara Prasad Pati, Siddhartha Datta Gupta, Asok Kumar Mukhopadhyay
STUDY DESIGN: Prospective observational cohort. OBJECTIVE: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). METHODS: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre...
January 16, 2018: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29337048/pathologic-findings-of-symptomatic-carotid-artery-stenosis-several-decades-after-radiation-therapy-a-case-report
#3
Shuichi Tonomura, Keiji Shimada, Naoko Funatsu, Yoshiaki Kakehi, Hisao Shimizu, Nobuyuki Takahashi
Improved long-term survival of malignancy has drawn increased attention to late cerebrovascular toxicity after neck radiotherapy. Recently, neck radiotherapy has been found as a significant risk factor of carotid artery stenosis and ischemic stroke; however, long-term adverse effects of radiation in large arteries remain unknown. Here, we described an autopsied case with recurrent ischemic stroke associated with ipsilateral carotid artery stenosis several decades after neck radiation therapy. Pathologically, there were intima-media fibrosis, endothelial cell loss, and decreased expression of thrombomodulin in irradiated carotid artery stenosis...
January 11, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29331940/screening-and-functional-exploration-of-prothrombin-arg596-related-mutations-in-chinese-venous-thromboembolism-patients
#4
Xi Wu, Lei Li, Qiulan Ding, Xuefeng Wang, Fang Wu, Wenman Wu
AIMS: Dysfunctional prothrombin residue Arg596 associated mutation has been found to precipitate venous thromboembolism (VTE). In the current study we investigated the prevalence of Arg596 associated mutations in Chinese patients with VTE and explored the functional impact of Arg596Gln mutation on coagulation function in affected patients. METHODS: Prothrombin clotting activity was measured in 267 unrelated patients with unprovoked VTE. Patients with moderately decreased activities underwent further analysis of the F2 gene...
January 13, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29323190/angiopoietins-bind-thrombomodulin-and-inhibit-its-function-as-a-thrombin-cofactor
#5
Christopher Daly, Xiaozhong Qian, Carla Castanaro, Elizabeth Pasnikowski, Xiabo Jiang, Benjamin R Thomson, Susan E Quaggin, Nicholas Papadopoulos, Yang Wei, John S Rudge, Gavin Thurston, George D Yancopoulos, Samuel Davis
Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are ligands for Tie2, an endothelial-specific receptor tyrosine kinase that is an essential regulator of angiogenesis. Here we report the identification, via expression cloning, of thrombomodulin (TM) as another receptor for Ang1 and Ang2. Thrombomodulin is an endothelial cell surface molecule that plays an essential role as a coagulation inhibitor via its function as a cofactor in the thrombin-mediated activation of protein C, an anticoagulant protein, as well as thrombin-activatable fibrinolysis inhibitor (TAFI)...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29296786/icam-1-targeted-thrombomodulin-mitigates-tissue-factor-driven-inflammatory-thrombosis-in-a-human-endothelialized-microfluidic-model
#6
Colin F Greineder, Ian H Johnston, Carlos H Villa, Kandace Gollomp, Charles T Esmon, Douglas B Cines, Mortimer Poncz, Vladimir R Muzykantov
Diverse human illnesses are characterized by loss or inactivation of endothelial thrombomodulin (TM), predisposing to microvascular inflammation, activation of coagulation, and tissue ischemia. Single-chain antibody fragment (scFv)/TM) fusion proteins, previously protective against end-organ injury in murine models of inflammation, are attractive candidates to treat inflammatory thrombosis. However, animal models have inherent differences in TM and coagulation biology, are limited in their ability to resolve and control endothelial biology, and do not allow in-depth testing of "humanized" scFv/TM fusion proteins, which are necessary for translation to the clinical domain...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295851/proteomic-profiling-for-cardiovascular-biomarker-discovery-in-orthostatic-hypotension
#7
Madeleine Johansson, Fabrizio Ricci, Nay Aung, Richard Sutton, Olle Melander, Artur Fedorowski
Orthostatic hypotension (OH) has been linked with higher incidence of cardiovascular disease, but little is known about the mechanisms behind this association. We aimed to identify cardiovascular disease biomarkers associated with OH through a proteomic profiling approach. Seven hundred seventy-eight patients with unexplained syncope or orthostatic intolerance underwent head-up tilt test and supine blood samples. Of these, 220 met diagnostic criteria of OH, and 179 demonstrated normal hemodynamic response during head-up tilt test...
January 2, 2018: Hypertension
https://www.readbyqxmd.com/read/29287059/microfluidics-a-high-throughput-system-for-the-assessment-of-the-endotheliopathy-of-trauma-and-the-effect-of-timing-of-plasma-administration-on-ameliorating-shock-associated-endothelial-dysfunction
#8
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Early resuscitation after trauma-hemorrhagic shock (HS) with plasma rather than crystalloid may ameliorate systemic endothelial cell (EC) injury and dysfunction (endotheliopathy of trauma [EOT]). We postulated that endothelial lined microfluidic networks would be a useful platform to study the endothelial cell activation/injury under flow conditions to mimic HS. We then used the microfluidic system to further characterize the protective effects and optimal timing of plasma infusion on the development of "EOT" in our model...
December 28, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29285085/unfractionated-heparin-protects-the-protein-c-system-against-lipopolysaccharide-induced-damage-in-vivo-and-in-vitro
#9
Dongmei Zhao, Renyu Ding, Yina Liu, Xiaohan Yin, Zhidan Zhang, Xiaochun Ma
Activation of protein C is greatly enhanced by the presence of thrombomodulin (TM) and endothelial protein C receptor (EPCR) on the endothelial surface. Impairment of the anticoagulant protein C system occurs during endotoxemia and contributes to sepsis-associated hypercoagulability. Previous studies have demonstrated that unfractionated heparin (UFH) can attenuate coagulation in endotoxemic mice. However, whether UFH has an effect on the protein C system remains to be elucidated. The current study evaluated the therapeutic effect of UFH on the protein C system in a mouse model of lipopolysaccharide (LPS)-induced sepsis, and further investigated the effect of UFH on the expression of TM and EPCR in vitro using human umbilical vein endothelial cells (HUVECs)...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29279488/tafro-syndrome-with-disseminated-intravascular-coagulation-successfully-treated-with-tocilizumab-and-recombinant-thrombomodulin
#10
Yusuke Takayama, Tetsuya Kubota, Yoshitaka Ogino, Hiroshi Ohnishi, Kazuto Togitani, Akihito Yokoyama
TAFRO syndrome is a systemic inflammatory disorder that is characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. Although thrombocytopenia is one of the major features of TAFRO syndrome, complications of disseminated intravascular coagulation (DIC) are not common. The therapeutic strategy for TAFRO syndrome complicated by DIC has not been established. We herein describe a case of TAFRO syndrome with DIC that was successfully treated with tocilizumab (an anti-IL-6 receptor antibody) and recombinant thrombomodulin (rTM)...
December 27, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29261771/endotheliopathy-is-associated-with-higher-levels-of-cell-free-dna-following-major-trauma-a-prospective-observational-study
#11
David N Naumann, Jon Hazeldine, Robert J Dinsdale, Jon R Bishop, Mark J Midwinter, Paul Harrison, Sam D Hutchings, Janet M Lord
BACKGROUND: Cell free deoxyribonucleic acid (cfDNA) has been proposed as a biomarker of secondary complications following trauma. Raised thrombomodulin and syndecan-1 levels have been used to indicate endotheliopathy, and are associated with inflammation, coagulopathy, and mortality. The current study aimed to analyse the association between cfDNA and biomarkers of endotheliopathy in a cohort of trauma patients, and whether raised levels of cfDNA were associated with poorer clinical outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/29246581/combined-therapy-with-gas-gangrene-antitoxin-and-recombinant-human-soluble-thrombomodulin-for-clostridium-perfringens-sepsis-in-a-rat-model
#12
Toru Hifumi, Daisuke Nakano, Joe Chiba, Motohide Takahashi, Akihiko Yamamoto, Yoshihide Fujisawa, Kenya Kawakita, Yasuhiro Kuroda, Akira Nishiyama
Cases of Clostridium perfringens septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group)...
December 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29234431/protective-effects-of-total-flavones-of-elaeagnus-rhamnoides-l-a-nelson-against-vascular-endothelial-injury-in-blood-stasis-model-rats
#13
Zhicheng Wei, Fang Zuo, Wenqian Wang, Li Wang, Dong Tong, Yong Zeng, Ping Wang, Xianli Meng, Yi Zhang
The aim was to evaluate the protective effects of total flavones of Elaeagnus rhamnoides (L.) A. Nelson (TFE) against vascular endothelial injury in blood stasis model rats and explore the potential mechanisms preliminarily. The model of blood stasis rat model with vascular endothelial injury was induced by subcutaneous injection of adrenaline combined with ice-water bath. Whole blood viscosity (WBV), histological examination, and prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234042/cfdna-correlates-with-endothelial-damage-after-cardiac-surgery-with-prolonged-cardiopulmonary-bypass-and-amplifies-netosis-in-an-intracellular-tlr9-independent-manner
#14
Adnana Paunel-Görgülü, Max Wacker, Mouhamed El Aita, Shoreshfan Hassan, Georg Schlachtenberger, Antje Deppe, Yeong-Hoon Choi, Elmar Kuhn, Thorsten O Mehler, Thorsten Wahlers
Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222696/thrombomodulin-favors-leukocyte-microvesicle-fibrinolytic-activity-reduces-netosis-and-prevents-septic-shock-induced-coagulopathy-in-rats
#15
Julie Helms, Raphaël Clere-Jehl, Elsa Bianchini, Pierrick Le Borgne, Mélanie Burban, Fatiha Zobairi, Jean-Luc Diehl, Lelia Grunebaum, Florence Toti, Ferhat Meziani, Delphine Borgel
BACKGROUND: Septic shock-induced disseminated intravascular coagulation is responsible for increased occurrence of multiple organ dysfunction and mortality. Immunothrombosis-induced coagulopathy may contribute to hypercoagulability. We aimed at determining whether recombinant human thrombomodulin (rhTM) could control exaggerated immunothrombosis by studying procoagulant responses, fibrinolysis activity borne by microvesicles (MVs) and NETosis in septic shock. METHODS: In a septic shock model after a cecal ligation and puncture-induced peritonitis (H0), rats were treated with rhTM or a placebo at H18, resuscitated and monitored during 4 h...
December 8, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/29218082/functional-characterization-of-cxcr4-in-mediating-the-expression-of-protein-c-system-in-experimental-ulcerative-colitis
#16
Xuhong Lin, Huichao Wang, Yuxia Li, Jingnan Yang, Ruilin Yang, Dandan Wei, Junjie Zhang, Desheng Yang, Bin Wang, Xuequn Ren, Guanchang Cheng
The present study aimed to explore the role of CXCR4 and protein C system (PCS) in the experimental ulcerative colitis (UC). The expression of CXCR3, CCR10, and CXCR4 in dextran sulfate sodium (DSS)-induced colitis mouse model was measured by immunohistochemistry and western blot analysis. In vitro studies with microvascular endothelial cells (MVECs) were performed. The expression of endothelial protein C receptor (EPCR) and thrombomodulin (TM) were detected by RT-PCR and western blot analysis. Activities of protein C (PC), protein S (PS), activated PC (APC) were evaluated in cells pre-treated with JNK inhibitor SP600125 and c-Jun silencing...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29212955/myeloperoxidase-derived-2-chlorofatty-acids-contribute-to-human-sepsis-mortality-via-acute-respiratory-distress-syndrome
#17
Nuala J Meyer, John P Reilly, Rui Feng, Jason D Christie, Stanley L Hazen, Carolyn J Albert, Jacob D Franke, Celine L Hartman, Jane McHowat, David A Ford
Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis. In sequential consenting patients with sepsis, free 2-ClFA levels were significantly associated with ARDS, and with 30-day mortality, for each log increase in free 2-chlorostearic acid...
December 7, 2017: JCI Insight
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
#18
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/29198692/successful-recombinant-thrombomodulin-treatment-for-thrombotic-microangiopathy-after-liver-transplantation-a-case-report
#19
T Motomura, T Yoshizumi, M Ohira, Y Mano, T Toshima, S Itoh, N Harada, N Harimoto, T Ikegami, Y Soejima, Y Maehara
Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29197958/immunohaemostasis-a-new-view-on-haemostasis-during-sepsis
#20
REVIEW
Xavier Delabranche, Julie Helms, Ferhat Meziani
Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the "principal suspects" of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets...
December 2, 2017: Annals of Intensive Care
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