Abstract:
INTRODUCTION:The activation of coagulation is recognized as a universal event in severe sepsis. Both antithrombin and thrombomodulin play pivotal roles as suppressors of coagulation. Since the levels of both anticoagulants decrease significantly, we hypothesized that a combination therapy would be beneficial. METHODS:A sepsis model was established using the intravenous infusion of lipopolysaccharide (LPS). Either 125 IU/kg of antithrombin, 0.25mg/kg of recombinant thrombomodulin, or a combination of both agents was injected immediately after LPS infusion (n=7 each), while only a physiological saline was injected in the control group (n=7). Blood samples were obtained at eight hours after LPS infusion, and organ damage markers and the plasma levels of damage-associated molecular patterns (DAMPs), such as histone H3 and cell-free DNA (cf-DNA), were measured. In another series, the leukocytes harvested from normal rats were cultured in plasma obtained from each group (n=7). Eight hours later, the leukocytes were stained with green fluorescent protein, Annexin V and 7-AAD, and the proportion of alive+apoptic/necrotic cells was calculated. RESULTS:Organ damage markers such as ALT and BUN were maintained best in the combination group (P<0.05). The circulating levels of histone H3 and cf-DNA were both significantly lower in the combination therapy group (P<0.01, 0.05, respectively). The proportion of alive+apoptic/necrotic cells was significantly higher in the combination therapy group (P<0.05). CONCLUSION:The coadministration of antithrombin and recombinant thrombomodulin can modulate cell death and decrease the circulating levels of histone H3 and cf-DNA, leading to protection against organ damage in a rat model of sepsis.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Iba T,Miki T,Hashiguchi N,Tabe Y,Nagaoka Idoi
10.1016/j.thromres.2014.04.015subject
Has Abstractpub_date
2014-07-01 00:00:00pages
169-73issue
1eissn
0049-3848issn
1879-2472pii
S0049-3848(14)00229-1journal_volume
134pub_type
杂志文章abstract::The need for anticoagulation in dialysis patients is common and the incidence of venous thromboembolism (VTE) and atrial fibrillation in this population is high. While direct data are lacking on the management of anticoagulation in dialysis patients, careful weighing of risks and benefits on the basis of evidence from...
journal_title:Thrombosis research
pub_type: 杂志文章,实务指引
doi:10.1016/j.thromres.2005.03.031
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVES:Dabigatran etexilate is widely used for stroke prevention in the patients with atrial fibrillation. The anticoagulation activity of dabigatran is not necessary monitored in routine clinical practice. We aimed to study the effect of dabigatran on thrombin generation (TG) and coagulation assays in rabbit and h...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.03.012
更新日期:2018-05-01 00:00:00
abstract::The prevention of venous thromboembolism (VTE) in women with cancer requires special consideration. The presence of cancer results in both non-surgical and surgical patients having increased risk of VTE. This usually leads to a modification of the recommended preventive therapy, affecting the type, dose and length of ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(11)70003-2
更新日期:2011-02-01 00:00:00
abstract::Activation of human platelets by PAF was augmented by C-reactive protein, an acute phase plasma protein. The concentration of PAF required for irreversible activation (secondary aggregation of platelet and release of serotonin) was decreased to 1/10 in the presence of C-reactive protein (CRP). The presence of CRP stim...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90361-0
更新日期:1986-03-01 00:00:00
abstract:INTRODUCTION:To validate the diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) at an early stage of trauma and to evaluate the hypothesis that the JAAM criteria can diagnose DIC with a higher sensitivity than the International Society ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.06.036
更新日期:2009-12-01 00:00:00
abstract::In spite of numerous studies on the involvement of fibrinogen in transendothelial migration of leukocytes and thereby inflammation, there is still no clear understanding of which fibrin(ogen) species can stimulate leukocyte transmigration. Although we have previously proposed that interaction of fibrin with the VLDL r...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.11.007
更新日期:2018-02-01 00:00:00
abstract::Recombinant forms of human antithrombin (AT) were expressed in COS-1 cells, and their interaction with human thrombin characterized by comparing the reactivity of two engineered mutant forms of AT with the wild-type recombinant. Both mutant forms contained single amino acid substitutions of Asp (G392D) or Pro (G392P) ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90240-2
更新日期:1994-08-01 00:00:00
abstract::Bovine hide collagen dispersions were swollen in the pH range 1.6-7.0, treated with glutaraldehyde, and dialyzed to neutral pH. The intensity with which these collagens reacted with human platelets in plasma was studied by aggregometry and scanning electron microscopy. Collagen swollen at a pH below 4.25 +/- 0.30 and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90463-5
更新日期:1989-07-01 00:00:00
abstract::This study focused on the clinical outcomes in multiple myeloma (MM) patients with venous thromboembolism (VTE) who received low-molecular-weight heparin (dalteparin) therapy. Changes in D-dimer levels before and after VTE were also evaluated. Among 549 patients treated with various chemotherapeutic agents, a total of...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.09.021
更新日期:2015-11-01 00:00:00
abstract::We report an inbred family with two cases of homozygous protein C deficiency and review 11 other such cases. Both patients presented in the second half of their first year of life with recurrent rapidly disappearing ecchymotic skin lesions, disseminated intravascular coagulation, and venous thrombosis. Successful trea...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/0049-3848(89)90202-8
更新日期:1989-03-01 00:00:00
abstract:INTRODUCTION:The A-subunit of blood coagulation factor XIII is a pro-transglutaminase, which cross-links α- and γ-fibrin-chains in its activated form. Selective inhibitors against FXIII-A may be desirable drugs to prevent the development of thromboses. Animal models are generally used for proof of principle and for tox...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.02.008
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Venous thromboembolism is a common cause of morbidity and mortality. Although cirrhosis has classically been considered as an acquired bleeding diathesis, there is increasing evidence that rejects the traditional belief that these patients are naturally protected against venous thromboembolism. However, an...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.thromres.2013.08.001
更新日期:2013-10-01 00:00:00
abstract:INTRODUCTION:Data regarding the clinical relevance of pulmonary infarction (PI) in patients with pulmonary embolism (PE) are lacking. The aim of this study was to investigate the clinical features of PE patients with PI and the prognostic role of PI for PE patients. MATERIALS AND METHODS:Based on computed tomography s...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.03.012
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVE:In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. Thus, clot stability might be a critical issue in the development of multiple organ dysfunction syndrome. Activated FXIII (FXIIIa) forms stable fibrin clots by covalently cross-linking fibrin monomers. Theref...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.thromres.2006.02.003
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The usefulness of coagulation tests performed before epidural analgesia for surgery or to alleviate labour pain is controversial. The aims of this study were: (1) to evaluate the prevalence of abnormal tests in a large cohort of healthy pregnant women and their association with epidural hematoma; (2) to asse...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.02.023
更新日期:2011-07-01 00:00:00
abstract::Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 9...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90118-v
更新日期:1990-09-15 00:00:00
abstract::Blackfoot disease is a unique endemic and chronic progressive arteriosclerotic vascular disease in southwest area of Taiwan. In this study, we determined the plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), urokinase plasminogen activator (uPA), and von Willebrand factor (vWF...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90188-t
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND:The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2016.05.019
更新日期:2016-07-01 00:00:00
abstract:INTRODUCTION:Ultrasound can accelerate clot dissolution in vitro and in vivo. We used an ex vivo canine shunt to investigate low frequency ultrasound effects on platelet-rich stent thrombosis. METHODS AND RESULTS:Nitinol stents were expanded to 2 mm in diameter in two perfusion chambers in a parallel shunt and exposed...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2003.10.023
更新日期:2003-01-01 00:00:00
abstract::Epsilon-amino-caproic acid (EACA) induces a clinically-useful anti-haemorrhagic, mildly thrombotic state while ellagic acid (EA) induces a severe hypercoagulable one. Reversal of these states may on occasion be necessary. The effectiveness of the antiplatelet drugs, aspirin and dipyridamole (ASA/D), in reducing thromb...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00098-9
更新日期:1996-06-15 00:00:00
abstract:INTRODUCTION:Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. MATERIALS AND METHODS:All adult patients that received off-label rFVIIa from 2005-2012 were inclu...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.02.026
更新日期:2014-05-01 00:00:00
abstract:UNLABELLED:We undertook a survey of French university hospital hematological laboratories to ascertain the clinical characteristics of patients with suspected HIT, the laboratory tests performed, and the therapeutic strategy adopted in current practice. METHODS:A standardized medical records database for patients with...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.02.003
更新日期:2010-06-01 00:00:00
abstract:INTRODUCTION:There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.07.039
更新日期:2014-11-01 00:00:00
abstract::The mechanistic paradigm underlying venous thrombosis at atypical locations stems from the observation that most events occur as a result of pathology of the organ system drained by the involved venous segment. Cerebral venous sinus thrombosis stands apart as an exception to this general rule. Although brain and sinus...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2010.04.015
更新日期:2010-08-01 00:00:00
abstract:INTRODUCTION:Warfarin is the most widely used oral anticoagulant. It has been suggested that anticoagulation effect of warfarin is significantly associated with the polymorphism of certain genes, including Cytochrome P450 complex subunit 2C9 (CYP2C9), Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), Gamma-Glutam...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.thromres.2009.10.017
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:Dabigatran etexilate is an oral direct thrombin inhibitor. Although routine anticoagulation monitoring with dabigatran is not usually required, a simple and precise laboratory test to measure dabigatran concentrations in patient plasma may be useful in certain clinical circumstances, such as emergency situ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.12.021
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVE:Exposure of the subendothelium to flowing blood following rupture of atherosclerotic lesions or during balloon angioplasty initiates platelet adhesion to the vascular wall. Because activated platelets release proinflammatory mediators (e.g., interleukin (IL)-1beta) and secrete growth factors, platelet adhesio...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(03)00342-6
更新日期:2003-06-01 00:00:00
abstract::Bovine myelin basic protein (BP) induced a shape change and endogenous phosphorylation of a 45,000 (45K) molecular weight protein of intact human platelets. This effect occurred rapidly over an effective concentration range of 5-100 microM BP. BP peptides encompassing residues 1-42, 43-88, and 89-169 from the BP molec...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90090-1
更新日期:1982-03-15 00:00:00
abstract::Several inflammatory particles (zymosan, two forms of asbestos, carrageenan) and the soluble inflammatory agent dextran sulphate induced a dose- and time-dependent increase in thromboplastin activity of cultured human monocytes. Two weakly inflammatory particles (latex and anatase) had little effect. The increase larg...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90227-x
更新日期:1983-05-15 00:00:00
abstract::Coronary artery disease (CAD) continues to be the most frequent cause of death among women in the United States. Although elevated levels of clotting factors have been associated with CAD, few of these studies have been performed in women. Elevated levels of Factor XI have previously been associated with venous thromb...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(02)00190-1
更新日期:2002-07-15 00:00:00