Abstract：
BACKGROUND: Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LEThrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, was completed. OBJECTIVE: This article assesses the benefits and harms of rhTM therapy in sepsis-induced coagulopathy by updating our previous systematic review. METHODS: We performed a systematic review and meta-analysis of rhTM therapy for sepsis-induced coagulopathy in randomized controlled trials. All-cause 28-day mortality as efficacy and serious bleeding complications as the adverse effect were measured as primary outcomes. We assessed the certainty of a body of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We analysed five trials enrolling 1,762 patients. Approximately 13% reduction in the risk of mortality was observed in the rhTM group, but the difference was not significant (relative risk, 0.87; 95% confidence interval, 0.74-1.03; p = 0.10; I2 = 0%). Risk of serious bleeding complications did not increase with rhTM administration. We judged the certainty of evidence as moderate for mortality and low for serious bleeding. Trial sequential analysis indicated that only 42.0% of the required information size is actually available at this stage to reject or accept low risk-of-bias trials examining the anticipated effect for all-cause mortality. CONCLUSION: Even in this updated review including the latest SCARLET trial, we currently cannot make any declarative judgments about the beneficial effects of rhTM in sepsis-induced coagulopathy, although some favourable effects were suggested.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Yamakawa K,Murao S,Aihara Mdoi
10.1055/s-0038-1676345subject
Has Abstractpub_date
2019-01-01 00:00:00pages
56-65issue
1eissn
0340-6245issn
2567-689Xjournal_volume
119pub_type
杂志文章,meta分析abstract：:LMWH preparations have been proven to be safe and effective in the out-patient management of acute DVT. Although LMWHs are more expensive than unfractionated heparin, the lack of need for laboratory monitoring of LMWHs and their potential for out-patient treatment more than offsets the drug related cost difference and...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:The object was to assess the variability in displayed International Normalised Ratio (INR) between monitors of the same manufacture using whole blood samples from the same subjects. Two brands of monitor, CoaguChek Mini and the TAS PT-NC were tested. 14 instruments of each brand were tested on the same day at the same...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：:Thrombospondin, a trimeric glycoprotein contained in the platelet alpha-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-04-08 00:00:00
abstract：:As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：1991-02-12 00:00:00
abstract：:A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 pat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-06-30 00:00:00
abstract：:We previously reported that antithrombin (AT) reduced ischemia/reperfusion (I/R)-induced liver injury in rats by increasing endothelial production of prostacyclin (PGI2). However, the mechanism(s) underlying this phenomenon remains to be fully elucidated. We also demonstrated that activation of capsaicin-sensitive sen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-02-0106
更新日期：2005-01-01 00:00:00
abstract：:Site directed mutagenesis was used to construct a t-PA variant that contains an additional glycosylation site in the first kringle domain (T103N) combined with a tetra-alanine substitution in the protease domain (KHRR 296-299 AAAA). This combination variant has a plasma clearance rate that is 4.5-fold slower in rats a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-08-02 00:00:00
abstract：:To add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical t...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-06-01 00:00:00
abstract：:Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plas...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-10-0874
更新日期：2015-06-01 00:00:00
abstract：:Treatment with the direct thrombin inhibitor argatroban (ARG) is often followed by vitamin K-antagonist treatment (VKA). Phenprocoumon (PC) and acenocoumarol (AC) are frequently used in Europe. The standard monitoring test for VKA, pro-thrombin time (PT), is prolonged by direct thrombin inhibitors. Therefore the Inter...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1160/TH03-12-0794
更新日期：2004-06-01 00:00:00
abstract：INTRODUCTION:Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1639585
更新日期：2018-05-01 00:00:00
abstract：:The administration of recombinant activated factor VII (rFVIIa) by continuous infusion has provided a safe and convenient alternative to bolus injections in haemophiliacs with inhibitors, but it has only been reported in a single case with congenital factor VII (FVII) deficiency. The results of 12 consecutive surgical...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1160/TH05-05-0342
更新日期：2005-12-01 00:00:00
abstract：:Cellular adhesion molecules also known as selectins promote recruitment of inflammatory cells into the arterial wall where they interact with lipid particles leading subsequently to plaque formation. The intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the endothelial-leuk...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-12-1014
更新日期：2015-08-31 00:00:00
abstract：:Elderly patients have previously been shown to have an increased plasma concentration of tissue plasminogen activator (t-PA) antigen (t-PA Ag). Since the concentration of t-PA Ag depends on both free t-PA and t-PA complexed with inhibitors, mainly plasminogen activator inhibitor (PA inhibitor), we have investigated th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-06-30 00:00:00
abstract：:Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-11-15 00:00:00
abstract：:Overexpression of plasminogen activator inhibitor-1 (SERPINE1, PAI-1), the major physiological inhibitor of pericellular plasmin generation, is a significant causative factor in the progression of vascular disorders (e.g. arteriosclerosis, thrombosis, perivascular fibrosis) as well as a biomarker and a predictor of ca...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2008-12-01 00:00:00
abstract：:The vast majority of thrombin (>95%) is generated after clotting is completed, suggesting that thrombin formation serves purposes beyond coagulation, such as tissue repair after vessel injury. Two types of vascular thrombin binding sites exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their express...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-09-0627
更新日期：2010-05-01 00:00:00
abstract：:Forty-two patients with total occlusion of a coronary vessel were treated with intracoronary fibrinolytic agents. Four therapeutic protocols were compared: group I received streptokinase (SK) as a continuous infusion; group II and III received SK as a bolus at different doses and group IV received lysplasminogen (Pg) ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1983-12-30 00:00:00
abstract：:Cysteinyl leukotrienes (i.e. LTC4, LTD4), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory process or atherosclerosis. We studied the effect of LTC4, LTD4, and LTE4 on the in vitro proliferation of rat VSMC, measured ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:In trauma patients, resuscitation treatment of intravascular volume may cause haemodilution including blood cell- and plasma-dilution. After plasma-dilution, fibrinogen is the first factor that decreases to critically low concentrations. Fibrin formed in lowered levels is susceptible to fibrinolysis, a natural forerun...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH13-06-0497
更新日期：2014-03-03 00:00:00
abstract：:Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), ant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH10-02-0091
更新日期：2010-08-01 00:00:00
abstract：:Microangiopathy and disseminated platelet aggregation have been reported in thrombotic thrombocytopenic purpura (TTP) and pregnancy-induced hypertension (PIH). Since unusually large von Willebrand factor (vWF) multimers have been implicated in the evolvement of TTP, we analyzed factor VIII/vWF parameters in patients w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-09-29 00:00:00
abstract：:Previously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a sim...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:Post-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis. To evaluate this hypothesi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-12-15 00:00:00
abstract：BACKGROUND: Evaluation of thromboembolic risk is essential in anticoagulated atrial fibrillation (AF) patients. The CHA2DS2-VASc score is largely validated and recommended by most guidelines. The GARFIELD-AF Stroke score has been proposed as an alternative risk score. METHODS: We analyzed warfarin-treated patients fro...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/a-1333-4448
更新日期：2020-12-09 00:00:00
abstract：:Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-02-0119
更新日期：2016-09-27 00:00:00
abstract：:Long noncoding ribonucleic acids (lncRNAs) have been defined as transcripts which are > 200 ribonucleotides in size and are not translated into protein. Recent work has shown that many lncRNAs do have specific molecular functions and biological effects, and are involved in a growing number of diseases, including ather...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0039-1692680
更新日期：2019-08-01 00:00:00
abstract：:Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in bin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-03-0135
更新日期：2006-09-01 00:00:00
abstract：BACKGROUND:Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VII:C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. METHODS AND RESULTS:We studied 208 cases of stroke whose pathological type was defined by cr...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:The functional activity and active site of plasmin in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen described in a previous paper. The functional activity of newborn plasminogen measured on chromogenic substrate w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
