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Angela Jerath, Qi Joy Yang, K Sandy Pang, Nikita Looby, Nathaly Reyes-Garces, Tijana Vasiljevic, Barbara Bojko, Janusz Pawliszyn, Duminda Wijeysundera, W Scott Beattie, Terrence M Yau, Marcin Wąsowicz
BACKGROUND: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations...
January 5, 2018: Anesthesia and Analgesia
Clara B Marschner, Bo Wiinberg, Inge Tarnow, Bo Markussen, Line Kühnel, Louise Bochsen, Annemarie T Kristensen
OBJECTIVE: To investigate parameters causing canine thromboelastographic hypercoagulability and to investigate whether thromboelastography (TEG) with Cytochalasin D (Cyt D) added is related to parameters of platelet activity. DESIGN: Prospective observational study on hemostatic and inflammatory parameters. Data were collected between November 2012 and July 2013. SETTING: University teaching hospital. ANIMALS: Twenty-eight dogs suffering from diseases predisposing to thrombosis and 19 clinically healthy dogs...
January 2018: Journal of Veterinary Emergency and Critical Care
Max Roy, Manuel Burggraf, Sven Lendemans, Herbert de Groot, Ricarda Rohrig
BACKGROUND: The plasmin/plasminogen inhibitor tranexamic acid (TXA) is mainly used in elective surgeries with a higher blood loss to avoid uncontrolled bleeding. Recently, TXA has also been shown to reduce mortality in trauma patients. It is assumed that its beneficial effects are principally caused by its antifibrinolytic properties. We hypothesize that TXA also improves survival in a modified Wigger's model of hemorrhagic shock by a mechanism other than antifibrinolysis. MATERIALS AND METHODS: Male Wistar rats were intermittently bled until the mean arterial blood pressure was dropped to 25-30 mm Hg (severe shock)...
February 2017: Journal of Surgical Research
Tingting Han, Guangping Zhang, Dong Yan, Hong Yang, Tonghui Ma, Zuguang Ye
Plasminogen activator inhibitor-1 (PAI-1) is a key negative regulator of the fibrinolytic system. Elevated levels of PAI-1 are associated with thrombosis and cardiovascular and metabolic diseases. Inhibition of PAI-1 activity represents a new strategy for antithrombotic and antifibrinolysis therapies. In this study, we systematically investigated the inhibitory effect of shikonin on PAI-1 activity. In the chromogenic substrate-based urokinase (uPA)/PAI-1 assay, we found that shikonin inhibited human PAI-1 activity with IC50 values of 30...
September 2016: Fitoterapia
Stephen M McHugh, Lavinia Kolarczyk, Robert S Lang, Lawrence M Wei, Marquez Jose, Kathirvel Subramaniam
BACKGROUND AND AIMS: Tranexamic acid (TA) is used for prophylactic antifibrinolysis in coronary artery bypass surgeries to reduce bleeding. We evaluated the efficacy of two different doses of TA for prophylactic antifibrinolysis in patients undergoing primary coronary artery bypass grafting (CABG) surgery in this retrospective cohort study at a tertiary care referral centre. METHODS: One-hundred eighty-four patients who underwent primary CABG with cardiopulmonary bypass (CPB) via sternotomy between January 2009 and June 2011 were evaluated...
February 2016: Indian Journal of Anaesthesia
Lin Xu, Wen-Kui Yu, Zhi-Liang Lin, Shan-Jun Tan, Xiao-Wu Bai, Kai Ding, Ning Li
Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic-vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. Male Sprague-Dawley rats were randomly assigned to sham, ATC control (ATCC) and ATC with sympathectomy by 6-hydroxydopamine (ATCS) group...
March 2015: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Liu Zhaohui, Guo Wanshou, Zhang Qidong, Zhu Guangduo
BACKGROUND: Blood management is critical in total knee arthroplasty (TKA). In bilateral, single stage TKA, blood loss seems more prominent. We believe it is important to control all potential bleeding within the wound tissue. PURPOSE: The purpose of the study was to evaluate a series of topical procedures used to reduce blood loss and transfusion in single-stage bilateral cemented total knee arthroplasty: antifibrinolysis with tranexamic acid, vasoconstriction with epinephrine, sealing of the bone section intraoperatively, and closure of the drainage tube within the first 4 h postoperatively...
November 2014: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
Wu Cong, Zhao Zhongxin, Li Tiangui, Yu Zhang, He Min, You Chao
AIM: To provide a quick evaluation of rebleeding risk based on the on-admission patient information and to guide the management of patients for better outcome. MATERIAL AND METHODS: A retrospective review of 630 consecutive cases of subarachnoid hemorrhage (SAH) at a major medical center was conducted, of which 458 were included for analysis. Sixty three cases of in-hospital pre-intervention rebleeding were identified. Chi-square or Mann-Whitney tests were used to screen for possible risk factors and values of the associated risk factors were assessed by logistic multivariate regression...
2012: Turkish Neurosurgery
Frederic T Billings, Mias Pretorius, Jonathan S Schildcrout, Nathaniel D Mercaldo, John G Byrne, T Alp Ikizler, Nancy J Brown
Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26...
July 2012: Journal of the American Society of Nephrology: JASN
Jonathan H Foley, Karl-Uwe Petersen, Catherine J Rea, Lori Harpell, Sandra Powell, David Lillicrap, Michael E Nesheim, Benny Sørensen
Solulin is a soluble form of thrombomodulin that is resistant to proteolysis and oxidation. It has been shown to increase the clot lysis time in factor VIII (fVIII)-deficient plasma by an activated thrombin-activatable fibrinolysis inhibitor (TAFIa)-dependent mechanism. In the present study, blood was drawn from humans and dogs with hemophilia, and thromboelastography was used to measure tissue factor-initiated fibrin formation and tissue-plasminogen activator-induced fibrinolysis. The kinetics of TAFI and protein C activation by the thrombin-Solulin complex were determined to describe the relative extent of anticoagulation and antifibrinolysis...
April 12, 2012: Blood
Daniel Dirkmann, Klaus Görlinger, Caroline Gisbertz, Fabian Dusse, Jürgen Peters
BACKGROUND: Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis...
June 2012: Anesthesia and Analgesia
H Chen, L Zhou, L Meng, M Liu, J Tan, L Gao, J Zhang
AIM: The aim of this study is to assess the changes in coagulation, thrombosis, anticoagulation, and fibrinolysis during early pregnancy. METHODS: One hundred and five pregnant women with monozygotic pregnancies between 10 and 12 weeks gestation were randomly enrolled as the study group, and another 82 non-pregnant women were selected as the control group. Coagulation parameters and prothrombotic state parameters were measured. RESULTS: Fg, F1 + 2, thrombin-antithrombin complex, GMP140, D-dimer, and plasminogen activator inhibitor 2 were statistically different between the study and the control groups (p < 0...
December 2011: Irish Journal of Medical Science
Tadayoshi Kosugi, Mariko Nakamura, Masanori Sunagawa
In the early phase of research, plasminogen activator inhibitor (PAI) was regarded as a negative regulator of fibrinolytic system, but the later study clarified that the changes in PAI level is closely related to risk factors of various pathologic processes of the lifestyle-related diseases. It is accepted that PAI-1 is a risk factor of the cardiovascular event in lifestyle-related diseases by recent researches analyzing the detailed function of PAI-1. In this review paper, we described the transition of pathophysiological significance of PAI based on many research papers especially from ours, which clarified the mechanism on protein expression of PAI, especially PAI-1...
April 2010: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Shogo Koshikawa, Toshio Nishikimi, Chikako Inaba, Kazumi Akimoto, Hiroaki Matsuoka
BACKGROUND: In this study, we tested the hypothesis that long-term Rho-kinase inhibition would reverse nitro-L-arginine methyl ester-exacerbated nephrosclerosis in spontaneously hypertensive rats and attempted to elucidate the mechanism involved. METHODS: Five groups (each n = 8) were studied: untreated spontaneously hypertensive rats; nitro-L-arginine methyl ester (50 mg/l in drinking water, for 3 weeks)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester with fasudil (10 mg/kg/day)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester for 3 weeks followed by fasudil for 3 weeks-treated spontaneously hypertensive rats (same doses), and nitro-L-arginine methyl ester for 3 weeks followed by untreated for 3 weeks...
September 2008: Journal of Hypertension
J B Walker, T M Binette, M Mackova, G R Lambkin, L Mitchell, L Bajzar
BACKGROUND: Carboxypeptidase N (CPN) is a constitutively active basic carboxypeptidase sharing specificity with activated thrombin-activable fibrinolysis inhibitor (TAFIa). Generally, CPN is regarded as being non-antifibrinolytic. However, this assumption has not been thoroughly investigated, particularly with respect to long-term antifibrinolysis. In addition, a recent report has shown that plasmin cleavage increases the catalytic activity of CPN. Therefore, we investigated the antifibrinolytic properties of CPN and plasmin-cleaved CPN (CPNc)...
May 2008: Journal of Thrombosis and Haemostasis: JTH
Toshio Nishikimi, Shogo Koshikawa, Yayoi Ishikawa, Kazumi Akimoto, Chikako Inaba, Kimihiko Ishimura, Hidehiko Ono, Hiroaki Matsuoka
OBJECTIVES: We examined whether the Rho/Rho-kinase pathway is involved in the pathogenesis of nephrosclerosis in severely hypertensive rats and assessed the effects of long-term treatment with a Rho-kinase inhibitor, fasudil, on kidney function, histological findings, gene expressions, and survival. We also attempted to elucidate the mechanisms involved. METHODS: We studied the following four groups: control Wistar-Kyoto rats (WKY), untreated salt-loaded spontaneously hypertensive stroke-prone rats (SHR-SP), low-dose fasudil (15 mg/kg per day)-treated SHR-SP, and high-dose fasudil (30 mg/kg per day)-treated SHR-SP...
May 2007: Journal of Hypertension
J B Walker, L Bajzar
BACKGROUND: The antifibrinolytic effect of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) and carboxypeptidase B (CPB) displays threshold behavior. When CPB was used to simulate conditions mimicking continuous TAFIa activity, it affected the lysis of plasma clots differently to clots formed from a minimal fibrinolytic system comprising fibrinogen, plasminogen and alpha(2)-antiplasmin. Whereas CPB saturably prolonged clot lysis in the purified system, the effect of CPB did not appear saturable in plasma clots...
June 2007: Journal of Thrombosis and Haemostasis: JTH
Nicholas L Smith, Lucia A Hindorff, Susan R Heckbert, Rozenn N Lemaitre, Kristin D Marciante, Kenneth Rice, Thomas Lumley, Joshua C Bis, Kerri L Wiggins, Frits R Rosendaal, Bruce M Psaty
CONTEXT: Although the roles of clotting proteins and enzymes that activate or inhibit fibrin production and lysis are well characterized, the underlying contribution of genetic variation in these constituents to risk of venous thrombosis (VT) has not been fully investigated. OBJECTIVE: To describe the association of common genetic variation in 24 coagulation, anticoagulation, fibrinolysis, and antifibrinolysis candidate genes with risk of incident nonfatal VT in postmenopausal women...
February 7, 2007: JAMA: the Journal of the American Medical Association
Toshio Nishikimi, Yosuke Mori, Kimihiko Ishimura, Yayoi Ishikawa, Shogo Koshikawa, Kazumi Akimoto, Naoto Minamino, Kenji Kangawa, Hiroaki Matsuoka
BACKGROUND: We and other investigators have reported that short- and long-term treatment with adrenomedullin has beneficial effects in heart failure. This study examined the effects of long-term treatment with a vasopeptidase inhibitor plus adrenomedullin in a model of heart failure in rats and assessed potential mechanisms of action. METHODS: Dahl salt-sensitive rats aged 11 weeks were randomly divided into three groups: an omapatrilat group, an omapatrilat plus adrenomedullin group, and an untreated group...
October 2006: American Journal of Hypertension
Dai-Yin Peng, Qing-Yun Liu, Min Dai, Xiao-Mei Zi, Xian-Xiang Xu
OBJECTIVE: To research the hemostatic effect of total saponins of Yinfenglun. METHOD: Bleeding time and volume were deteminded in mice after tails being cut. Clotting times were researched on mice, rats and dogs. Hemostatic mechanism total saponins of Yinfenglun were studied on plasma recalcified time, PT, KPTT and ELT. RESULT: TSY at different doses could markedly shorten bleeding time, reduce bleeding volume in mice. TSY also could shorten clotting time of mouse, rat and dog...
June 2005: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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