Abstract:
:Our aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid" (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of "rapid" metabolisers on 75 mg of clopidogrel within 30-208 (PRU) of P2Y12 inhibition is non-inferior to "slow" metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of "rapid" and "slow" metabolisers within 30-208 PRU of P2Y12 inhibition was 71% and 56.9%, respectively, an absolute difference of +14.1% (95% CI, -0.05% to 28.28%) with a non-inferiority margin greater than the predefined margin of -10%. Among patients out of target, all but one "slow" metabolisers displayed low-on prasugrel platelet reactivity while the majority of "rapid" metabolisers (68%) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30-208 PRU of P2Y12 inhibition was 83.6% and 79.3% in "rapid" and "slow" metabolisers, respectively (+4.3%, 95% CI -7.3% to 15.9%). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Collet JP,Kerneis M,Hulot JS,O'Connor SA,Silvain J,Mansencal N,Brugier D,Abtan J,Barthélémy O,Vignalou JB,Payot L,Rousseau H,Vicaut E,Montalescot G,GAMMA Investigators.doi
10.1160/TH15-05-0394subject
Has Abstractpub_date
2016-01-01 00:00:00pages
382-91issue
2eissn
0340-6245issn
2567-689Xpii
15-05-0394journal_volume
115pub_type
杂志文章,多中心研究abstract::Inflammation and thrombosis, two processes influencing each other, are involved in the pathogenesis of cerebrovascular disease. We showed that in patients with acute ischaemic stroke circulating platelets are activated and exhausted. To identify whether activated haemostasis might be cause or effect, we investigated t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-09-0620
更新日期:2010-06-01 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::Lipid oxidation products and in particular oxidized phospholipids (OxPL) are increasingly recognized as inducers of chronic inflammation characteristic of atherosclerosis. OxPL stimulate production of chemokines and adhesion of monocytes to endothelial cells. However, accumulating data suggest that, in addition to the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND: Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0039-1693740
更新日期:2019-11-01 00:00:00
abstract::Reactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand's disease (vWd). One quinine-dependent antibody (Q.Ab) caused platelet aggregation and [14C] serotonin release with only 7 of 12 normal donors,...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-02-28 00:00:00
abstract::Human endothelial cells isolated from umbilical cords were solubilized in Triton X-100 and examined by crossed immunoelectrophoresis using rabbit antiserum against endothelial cells. Endogenous labelling of the endothelial cell proteins with 14C-mannose followed by crossed immunoelectrophoresis and autoradiography rev...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-04-12 00:00:00
abstract::In a preliminary study, we have demonstrated that tissue factor (TF) is immunohistochemically stained in monocytes from patients with disseminated intravascular coagulation (DIC) but not from healthy volunteers, and that leukocytes from DIC patients induce enhanced activated factor X (FXa) generation in the presence o...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::CD36, also known as GPIIIb or GPIV, is a main protein of the platelet membrane. Accumulating evidence implicates CD36 in the pathogenesis of atherosclerosis. CD36 binds to cholesteryl-hemisuccinate coupled to agarose. This binding may be of physiologic relevance since CD36 has a long extracellular hydrophobic region a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Hirudin is a potent thrombin inhibitor derived from the leech Hirudo medicinalis salivary gland which has considerable potential for therapeutic use in thrombotic disease. The major risk attendant its use is hemorrhage. This study investigates the hypothesis that the prohemostatic effects of DDAVP infusion can curtail...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Filtration through asbestos filter (Seitz) of human plasma modified the prothrombin molecule as previously shown. Factor II could no longer be activated by physiological activators (Ca++ + phospholipid + V and Xa) but reacted readily with staphylocoagulase. The separation and purification of the modified prothrombin a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-02-15 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Glu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound satura...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-10-28 00:00:00
abstract::S. aureus produces and secretes a protein, extracellular fibrinogen binding protein (Efb), which contributes to virulence in wound infection. We have shown here that Efb is a potent inhibitor of platelet aggregation. Efb can bind specifically to platelets by two mechanisms; 1) to fibrinogen naturally bound to the surf...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-05-0287
更新日期:2004-04-01 00:00:00
abstract::The effects of mental stress (a colour word conflict test, CWT) and adrenaline infusions (0.1 and 0.4 nmol kg-1 min-1) on t-PA activity, t-PA antigen, PAI-1 activity and PAI-1 antigen were studied in 18 healthy male volunteers. Furthermore, the effects of metoprolol (200 mg/day during 1 week) or placebo (double-blind ...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1990-06-28 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::We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-10-31 00:00:00
abstract::The effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-06-30 00:00:00
abstract::Although venous thromboembolism (VTE) is a leading cause of maternal mortality, there is a paucity of real-world clinical data on clinical presentation and management of VTE during pregnancy and postpartum period. Using data from the international RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry, pre...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1714211
更新日期:2020-10-01 00:00:00
abstract::Interactions between proteins and heparin(-like) structures involve electrostatic forces and structural features. Based on charge distributions in the linear sequence of protein C inhibitor (PCI), two positively charged regions of PCI were proposed as possible candidates for this interaction. The first region, the A+ ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::The fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assign...
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:1996-12-01 00:00:00
abstract::Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
abstract::Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weight...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-11-0795
更新日期:2013-03-01 00:00:00
abstract::Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether t...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:10.1160/TH08-03-0172
更新日期:2008-07-01 00:00:00
abstract::Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::Central venous access devices are often essential for the administration of chemotherapy to patients with malignancy, but its use has been associated with a number of complications, mainly thrombosis. The true incidence of upper extremity deep vein thrombosis (DVT) in this setting is difficult to estimate since there ...
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:1996-02-01 00:00:00
abstract::Prasugrel, through its active metabolite, reduces atherothrombosis and its clinical manifestations by inhibiting platelet activation and aggregation. Platelets also contribute to inflammation through interaction with different classes of leukocytes. We investigated whether the inhibitory effect of prasugrel on platele...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-12-0867
更新日期:2012-06-01 00:00:00
abstract::Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1676520
更新日期:2019-01-01 00:00:00
abstract::Increased fibrinogen concentration is a well known phenomenon following acute ischemic stroke. However, the natural course of this hyperfibrinogenemia is uncertain. We aimed to clarify whether it is of a transient or more persistent nature in patients who harbor an underlying morbid biology of atherothrombo-inflammati...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0484
更新日期:2008-01-01 00:00:00
abstract::Plasma levels of D-dimer have been found useful as a marker of deep venous thrombosis in those patients in whom thrombosis is suspected, but their usefulness in postoperative screening is less clear. We have investigated the relationship of D-dimer to deep venous thrombosis in 90 patients after total hip and knee arth...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Serum amyloid P component (SAP), and its acute phase homologue C-reactive protein (CRP), prolonged activated partial thromboplastin times (APTT) in cell free plasma when assayed at physiological concentrations in the presence of heparin. SAP also inhibited clot formation initiated through the extrinsic and terminal ph...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-06-30 00:00:00