Abstract：
:Sepsis triggers a complex series of pathophysiologic events involving inflammatory responses and coagulation abnormalities. While circulating blood platelets are well-characterized for their contributions to coagulation, increasingly platelet-dependent effects on inflammation are being recognized. Here, we focus on the platelet membrane receptor, glycoprotein VI (GPVI), and its role in platelet microparticle (pMP) release. The GPVI receptor is a platelet-specific collagen membrane receptor that, upon ligand binding, facilitates the release of pMPs. As membrane-bound platelet fragments of less than 1 μm, pMPs are known to have both pro-inflammatory and pro-coagulant properties. Thus, pMPs are potentially impacting sepsis at multiple stages of the inflammatory response. Studies are presented documenting the impact of the most common GPVI haplotypes, GPVIa and GPVIb, on pMP levels and release in healthy individuals (n = 49). The GPVIa haplotype corresponds to an approximately twofold increase in circulating pMPs as a percentage of total microparticles in healthy individuals along with a heightened in vitro release of pMPs. Additionally, patients admitted to a paediatric intensive care unit (ICU) (n = 73) with an initial diagnosis of sepsis were recruited and their GPVI haplotypes determined. Septic patients of the GPVIa haplotype (n = 59) were statistically more likely to present with a diagnosis of severe sepsis or septic shock, as compared with GPVIb individuals (n = 14). Independent disease classification via PELOD-2 and Pediatric Risk of Mortality III scores confirmed individuals with the GPVIa haplotype were more likely to have significant organ failure. Thus, GPVI haplotypes influence pMP levels in the circulation and are predictive of sepsis severity when presenting to the ICU.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Asfari A,Dent JA,Corken A,Herington D,Kaliki V,Sra N,Hefley G,Pasala S,Prodhan P,Ware Jdoi
10.1055/s-0038-1676794subject
Has Abstractpub_date
2019-03-01 00:00:00pages
431-438issue
3eissn
0340-6245issn
2567-689Xjournal_volume
119pub_type
杂志文章abstract：:Platelet aggregation and adenine nucleotides in platelets have been studied in thirteen patients with myeloproliferative disorders. ADP induced aggregation was abnormal in two patients, but collagen induced aggregation was impaired in 11 patients. The concentrations of ATP and ADP in resting platelets in the patients ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1979-06-30 00:00:00
abstract：:The technique of crossed immunoelectrophoresis has been used to study the binding to purified antithrombin III (At III) of heparin and other mucopolysaccharides. The technique was unable to detect differences among samples of whole heparin from various manufacturers, but proved useful in studying the binding of hepari...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-02-29 00:00:00
abstract：:In order to explore the mechanisms leading to conformational changes of the vitronectin receptor alphavbeta3 following ligand or divalent cation binding, we have investigated the expression of epitopes known as ligand-induced binding sites (LIBS) on beta3 cytoplasmic tail mutants expressed in CHO cells. Truncation of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：BACKGROUND: Carotid atherosclerosis is an important cause of stroke. Intra-plaque haemorrhage (IPH) on magnetic resonance imaging (MRI) increases stroke risk. Development of IPH is only partly understood. Thrombin is an essential enzyme in haemostasis. Experimental animal studies have shown conflicting results on the r...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1055/s-0038-1666858
更新日期：2018-08-01 00:00:00
abstract：:Pathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins; Yops) into immune cells. Yops often exer...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2007-09-01 00:00:00
abstract：:We have investigated the role of two vasoactive substances, nitric oxide (NO)and endothelin (ET), in the pathophysiology of disseminated intravascular coagulation (DIC), using two types of DIC models. Experimental DIC was induced by sustained infusion of 0.1, 1, 10, or 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg t...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：:When adenosine diphosphate (ADP) is added to hirudinized platelet-rich plasma (PRP) in which the level of platelet cAMP has been pharmacologically elevated, there is an initial rapid fall in the level of cAMP brought about by inhibition of adenylate cyclase. This may be followed by a subsequent activation of adenylate...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-08-01 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：:The effect of the ADP receptor antagonists ATP and adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and the ADP-utilizing enzyme systems creatine phosphokinase/creatine phosphate (CPK/CP) and pyruvate kinase/phosphoenol pyruvate (PK/PEP) on platelet deposition onto type I collagen was examined. An in vitro ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-04-02 00:00:00
abstract：:It has been experimentally shown that endotoxin induces a significant increase in the blood levels of a plasminogen activator inhibitor (PAI). We evaluated the effect of different doses of heparin (5 to 20 IU kg-1 h-1), antithrombin III (10 to 40 U kg-1 h-1 and 240 U/kg as bolus) and of a combination of the two on: 1)...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-09-29 00:00:00
abstract：:Lysosomal Associated Membrane Protein-2 (LAMP-2) is an inherent component of lysosomal granule membranes in diverse cell types, including platelets. We examined platelets for evidence of LAMP-2 in dense granule membranes as CD63 has previously been shown to be present in both lysosomal and dense granule membranes. Imm...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:An alternative method of uniting small diameter vessels to obtain tissue union while limiting the thrombogenic effect of suture placement at a vessel anastomosis involves the use of a thrombin based fibrin glue as a surgical sealant. This investigation addresses whether the in vitro application of a thrombin based glu...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：:Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B2 (11-DH-TXB2) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:The alphaIIbeta3 receptor (GPIIb/IIIa) is the only platelet-specific integrin receptor and the most abundant adhesion/aggregation receptor on the surface of human platelets. Since mice are increasingly being used as models of human disease, we analyzed the structure and function of murine platelet alphaIIbeta3, utiliz...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:The aim of the present study was to evaluate the relative performance of five screening methods for APC resistance caused by the factor V:Q506 mutation: the original method Coatest APC Resistance Chromogenix, a modified method using the same reagents but a predilution 1+4 of the plasma in a factor V deficient plasma f...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:Human platelets have unique and reproducible mRNA profiles, with evidence for distinct profiles in haematopoietic stem cell disorders associated with thrombocytosis. Platelet transcript profiling is traditionally studied by microarray analysis, quantitative reverse transcription-PCR or serial analysis of gene expressi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-11-01 00:00:00
abstract：:Advanced electronic alerts (eAlerts) and computerised physician order entry (CPOE) increase adequate thromboprophylaxis orders among hospitalised medical patients. It remains unclear whether eAlerts maintain their efficacy over time, after withdrawal of continuing medical education (CME) on eAlerts and on thromboproph...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-04-0220
更新日期：2011-10-01 00:00:00
abstract：:Some correlations between plasma and platelet fatty acids (FA) were evaluated "ex vivo" in 94 normal subjects. The highest relationships between total FA from plasma and platelets were found for 18:1 (r = 0.74) and 18:2 (r = 0.67). Low correlations were obtained for free fatty acids (FFA). The most significant correla...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-12-29 00:00:00
abstract：:The endocannabinoid anandamide (AEA) has many neurovascular activities. However, it is not yet clear how AEA can be metabolized at the neurovascular interface, and how it can move through the vascular and the cerebral compartments. The results reported in this article show that isolated bovine brain microvessels, an e...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-01-01 00:00:00
abstract：:Moderate or severe paravalvular regurgitation after transcatheter aortic valve implantation (TAVI) is frequently associated with a loss of high-molecular-weight multimers of von Willebrand factor (VWF) and a reduced VWF collagen-binding capacity. It is unclear whether this phenomenon can also be observed in patients w...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：10.1160/17-07-0506
更新日期：2018-01-01 00:00:00
abstract：:Despite years of research and efforts to translate stroke research to clinical therapy, ischaemic stroke remains a major cause of death, disability, and diminished quality of life. Primary and secondary preventive measures combined with improved quality of care have made significant progress. However, no novel drug fo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH14-05-0448
更新日期：2014-11-01 00:00:00
abstract：:Prothrombin complex concentrates (PCC) are known to carry a risk of thromboembolism. We have chosen to reassess the problem of detecting in vivo signs of activation of the clotting mechanism by assaying fibrinopeptide A (FpA) after PCC administration in hemophilic patients during bleeding episodes. FpA was significant...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-10-31 00:00:00
abstract：:Fibrin polymerisation is mediated by interactions between knobs 'A' and 'B' exposed by thrombin cleavage, and holes 'a' and 'b'. We demonstrated markedly delayed thrombin-catalysed fibrin polymerisation, through B:b interactions alone, of recombinant γD364H -fibrinogen with impaired hole 'a'. To determine whether reco...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH12-09-0684
更新日期：2013-02-01 00:00:00
abstract：:The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged im...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH09-10-0685
更新日期：2010-09-01 00:00:00
abstract：:Antiphospholipid syndrome (APS) is an acquired thrombophilia with an uncertain role in the development of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess the association of APS with the clinical phenotype of CTEPH. We retrospectively reviewed data of CTEPH patients referred to our center. Cli...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0039-1692428
更新日期：2019-09-01 00:00:00
abstract：:Electrospray ionisation mass spectrometry was used to probe the structure of the new N-linked oligosaccharide in fibrinogen Kaiserslautern (gamma 380 Lys-->Asn). The mass increase of 2177 Da in the new beta chain indicated the attachment of a fully sialylated biantennary oligosaccharide on the new Asn residue; the exp...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Novel P2Y12 inhibitors are in development to overcome the occurrence of atherothrombotic events associated with poor responsiveness to the widely used P2Y12 inhibitor clopidogrel. Cangrelor is an intravenously administered P2Y12 inhibitor that does not need metabolic conversion to an active metabolite for its antiplat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-06-0367
更新日期：2010-02-01 00:00:00
abstract：:It was the objective of this study to determine whether reduced cleavage of von Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a consequence of reduced shear stress or postoperative changes in VWF cleavage protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by acquired...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-12-0803
更新日期：2012-07-01 00:00:00
abstract：:Microvascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly i...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-08-30 00:00:00
abstract：:We investigated the molecular basis for factor VII (FVII) deficiency in Israel and found that 13 patients were homozygous and 10 heterozygous for a C to T substitution at nucleotide 10648 of the FVII gene. This predicted an Ala244Val change and was associated with decreased FVII activity and antigen level. Of the 36 A...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
