Abstract:
:A high throughput 384-well plate assay of blood function in 60 microl reactions with the fluorogenic thrombin substrate, boc-VPR-MCA, allowed for real-time monitoring of coagulation under a diverse set of reaction conditions. Using recalcified, citrated whole blood diluted 3-fold with corn trypsin inhibitor (to block Factor XIIa), addition of 0 to 13.8 pM of tissue factor (TF) reduced the time of maximal rate of thrombin production T(max) from 45 min to 11 min. Over this range of TF,T(max) was reduced from 35 min to 6 min by co-addition of 10 nM convulxin to activate platelets via GPVI. The maximal rate of thrombin production at T(max) was not a function of exogenously-added TF,Va, or reVIIa, but increased 30% with added convulxin. Addition of 0.07 to 0.7 pM TF along with convulxin produced small, but detectable reductions in T(max). Addition of up to 0.67 nM reVIIa reduced T(max) by up to 53% in the range of 0.7 to 7 pM TF. Interestingly, platelet factor 4 (2.7 microM) caused a prolongation of T(max) from 45 min to 78 min at 0 TF, while protamine (1.8 microM) reduced T(max) to 30 min at 0 TF. Finally, combinatorial reaction studies with exogenously-added ADP, histamine, fMLP, indomethacin, anti-CD18, and fibrinogen revealed no unusual synergies amongst the agents, but demonstrated a striking procoagulant activity of added fibrinogen, due to protease contaminants in the "purified" fibrinogen. This high throughput approach allowed automated profiling of blood (50 reactions/ml of blood) to generate large data sets for testing cellular-proteomic kinetic models, screening drug interactions, and potentially monitoring subtle changes in the functional phenotype of a patient blood sample.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Lo K,Diamond SLdoi
10.1160/TH04-03-0154keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
874-82issue
4eissn
0340-6245issn
2567-689Xpii
04100874journal_volume
92pub_type
杂志文章abstract::The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 micrograms/kg/min continuous infusion) or hep...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Human antithrombin III was purified from fresh human plasma by affinity chromatography on heparin-Sepharose, affinity chromatography on concanavalin A Sepharose, gel filtration on Ultrogel AcA 34, ion exchange chromatography on DEAE A-50 Sephadex and preparative agarose gel electrophoresis. The hydrolytic activity of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-06-30 00:00:00
abstract::Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/THS10-11-0720
更新日期:2011-05-01 00:00:00
abstract::Atherosclerosis and its clinical manifestations (i.e. myocardial infarction, stroke) are major causes of mortality and morbidity in Western countries. Endothelial dysfunction is considered the first step in the cascade leading up to coronary events. Increasing evidence suggests that direct inhibition of thromboxane A2...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH10-03-0195
更新日期:2010-11-01 00:00:00
abstract::Thrombin incubated with 2,3-diphosphoglycerate (150 nmol 2,3-DPG/1 NIH thrombin unit) lost up to 70% of its clotting activity, whereas the esterase activity remained unchanged. No fibrinopeptide release by thrombin was observed in the presence of 2,3-DPG. The fibrin polymerization was normal. By chromatography on Ambe...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-10-01 00:00:00
abstract::The German Priority Research Program "Angiogenesis" (www.angiogenese.de) hosts a biannual meeting in the Kloster Seeon in Southern Germany. The 2nd Kloster Seeon Meeting "Angiogenesis: Molecular Mechanisms and Functional Interactions" was held in September 2002. It included sessions on hypoxia, the biology of endothel...
journal_title:Thrombosis and haemostasis
pub_type:
doi:
更新日期:2003-01-01 00:00:00
abstract::A double antibody competition radioimmunoassay was developed that allowed to detect specifically as little as 15 ng antithrombin III (AT III) per ml of the assayed material. In normal plasma examined by this assay, AT III concentration averaged 199 +/- 21 micrograms/ml. Complexes of AT III with thrombin or factor Xa c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-02-28 00:00:00
abstract::Causative mutations in the factor VIII gene of seven unrelated patients with severe haemophilia A were identified using the mutation screening procedure conformation sensitive gel electrophoresis (1) and characterised by direct sequencing. Female family members of all patients had requested either carrier status deter...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic fu...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Early treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH05-04-0286
更新日期:2006-02-01 00:00:00
abstract::Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Human fibrinogen was subjected to limited proteolytic attack by thrombin, batroxobin or Agkistrodon contortrix thrombin-like enzyme, yielding desAB-, desA- or desB-fibrin monomers, respectively. Turbidity curves demonstrated that, with all three enzymes, the polymerization process was strongly accelerated by increasin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-04-30 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::Tissue factor pathway inhibitor (TFPI) plays a crucial role in haemostasis by regulating TF-induced initiation of coagulation. Since it is expressed by endothelial and trophoblastic cells, TFPI is of particular importance at the placental level and might be involved in the occurrence of gestational vascular complicati...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-06-0399
更新日期:2011-01-01 00:00:00
abstract::The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained ...
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:1994-12-01 00:00:00
abstract::Inherited thrombophilia has been shown to be linked with fetal loss. We performed a case-control study on the association between thrombosis-related polymorphisms in the factor V (FV) gene (Leiden, Cambridge, Hong Kong; HR2 haplotype) and idiopathic recurrent pregnancy loss (RPL) in Tunisian women. A total of 348 wome...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::It is known that the fibrinolysis inhibitors in the human placenta are proteins which, in vitro, block urokinase plasminogen activation and are for this reason called urokinase inhibitors. In the present study it was found, for the first time, that a slow-molecular urokinase inhibitor also occurs in the human placenta...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-02-29 00:00:00
abstract::In 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, alpha-granule release (represented by beta-thromboglobulin [beta TG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-02-03 00:00:00
abstract::Existing clinical scores do not perform well in predicting bleeding in elderly patients with acute venous thromboembolism (VTE). We sought to derive an easy-to-use clinical score to help physicians identify elderly patients with VTE who are at high-risk of bleeding during extended anticoagulation (>3 months). Our deri...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH-17-03-0162
更新日期:2017-08-24 00:00:00
abstract::Activation and signaling of circulating blood and vessel wall cells, as well as their direct adhesive interactions, are critical for the regulation of vascular homeostasis related to vasomotor responses, inflammation, hemostasis, and wound repair. Under conditions of stress, inflammation, or infection the targeting an...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-08-01 00:00:00
abstract::We have identified a patient with a dysfunctional prothrombin that we have designated Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level of 13% and 20% compared to normal controls using two different assays with a normal prothrombin antigen level of 91% of normal controls. The genetic...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic fun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1660479
更新日期:2018-07-01 00:00:00
abstract::Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical development. The primary objective of the present study was to assess the pharmacodynamics (PD) and safety of enoxaparin 1 mg/kg followed 12 hours (h) post-dose by edoxaban 60 mg, which is the regimen being used in the phase III study of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH11-09-0676
更新日期:2012-07-01 00:00:00
abstract::ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and AD...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0683
更新日期:2004-12-01 00:00:00
abstract::Mechanisms mediating initial adsorption of coagulation proteins to live cells were investigated. Adsorption kinetics were examined under varying flow conditions using tracer-dilution techniques in perfused spherical monolayers of cells expressing tissue factor. At biologically relevant time and concentration ranges, r...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::It is conceivable that the extent and spatio-temperal expression of dozens or even a few hundred genes are significantly altered during the development and progression of atherosclerosis as compared to normal circumstances. Differential gene expression in vascular cells and in blood cells, due to gene-gene and gene-en...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::Prevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. T...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-08-31 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells and plays a central role in angiogenesis and vasculogenesis. Therefore, VEGF and its receptors VEGFR-1 and VEGFR-2 are prime targets for anti-angiogenic intervention which is thought to be one of the most promising approaches in cancer...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-02-0106
更新日期:2003-09-01 00:00:00
abstract::A genetically-transmissible factor (F) XII-inactivated allele has been produced in mice by targeted replacement of exons 3-8 of the FXII gene with the neomycin resistance gene. Interbreeding of these mice provided offspring homozygous for two inactivated FXII alleles (FXII(-/-)). Male and female FXII-deficient mice br...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-03-0128
更新日期:2006-06-01 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