Abstract:
:ACS patients undergoing percutaneous coronary intervention (PCI) when treated with bivalirudin and clopidogrel had increased frequency of early stent thrombosis. 24 patients referred for intervention with planned bivalirudin therapy, not previously treated with a P2Y12 inhibitor and not receiving heparins or αIIbβ3 inhibitors were randomized to treatment with either clopidogrel (600 mg) or prasugrel (60 mg). Platelet aggregation (PA) was measured by light transmission aggregometry (LTA) of platelet-rich plasma in response to ADP, PAR1/PAR4 thrombin receptor agonists and collagen at baseline and at 1, 2, 4 and 16 h following the cessation of bivalirudin infusion. Prasugrel-mediated inhibition of PA was significantly greater than that of clopidogrel at all time points for ADP as well as PAR1. There was an unanticipated, significantly greater protection of PAR4-mediated platelet aggregation only detected with prasugrel and not observed with clopidogrel. We further examined the effect of the hyperreactive PAR4 Thr120 variant in the protease-activated receptor 4 (PAR4), single nucleotide polymorphism (SNP) rs773902 on aggregation protection. The PAR4 protective effect with prasugrel was lost in individuals carrying the PAR4 Thr120 variant, and not in Ala120 homozygote. PAR1, ADP and collagen inhibition was not significantly affected in the hyperreactive PAR4 Thr120 variant. We documented that the P2Y12 ADP receptor-mediated regulation of the strength of the high-affinity conformation of αIIbβ3 as detected by PAC-1 ab, and in control of platelet adhesiveness through Rap1 GTPase protein activation. Importantly, the PAR4 Thr120 variant resulted in the increased rate and magnitude of Rap1 activation. Human platelet PAR4 mediated-activation of αIIbβ3 was phospholipase C beta (PLCβ)-dependent and unlike mouse platelet PI3K-independent. These data identify a PAR4-dependent inhibitory mechanism for the prasugrel-mediated platelet inhibition, not seen with clopidogrel that could explain the reduction in stent thrombosis documented in clinical trials with prasugrel.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Kimmelstiel C,Stevenson R,Nguyen N,Van Doren L,Zhang P,Perkins J,Kapur NK,Weintraub A,Castaneda V,Kuliopulos A,Covic Ldoi
10.1016/j.thromres.2019.01.017subject
Has Abstractpub_date
2019-05-01 00:00:00pages
59-69eissn
0049-3848issn
1879-2472pii
S0049-3848(19)30026-Xjournal_volume
177pub_type
杂志文章abstract::Forty women undergoing surgery under general anaesthesia for hyperplasia mammae were randomized to treatment with low dose heparin (5000 IU twice daily) or not. Preoperatively, and repeated on the 3. postoperative day, assays of euglobulin clot lysis time (ELT) after venous stasis, tissue plasminogen activator (t-PA) ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(87)90318-5
更新日期:1987-03-01 00:00:00
abstract::Eicosapentaenoic acid (EPA) has been reported to have a potent anti-aggregatory activity and to be efficiently metabolized by 12-lipoxygenase, not by cyclooxygenase in platelets. In vitro effect of 12-lipoxygenase metabolites of EPA on platelet function was studied and compared with those of arachidonic acid (AA). The...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90248-3
更新日期:1986-02-01 00:00:00
abstract::Activated platelets secrete different chemokines, among others CCL5, thereby triggering inflammatory cell recruitment into the vessel wall. Here, we investigated how CCL5 deficiency influences vascular remodeling processes. Experiments were performed in apolipoprotein E and CCL5 double deficient (ApoE(-/-)×CCL5(-/-)) ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2016.06.013
更新日期:2016-08-01 00:00:00
abstract::The perfusion technique to measure the relative adhesive and thrombogenic indices of vascular prostheses by a quantitative scanning electron microscopy has been described. To normalize the experiments with different samples of plasma we compared the adhesive and thrombogenic properties of the analyzed prostheses with ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90038-5
更新日期:1983-02-01 00:00:00
abstract::The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 1...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90297-x
更新日期:1985-12-01 00:00:00
abstract:INTRODUCTION:Cell surface thiol isomerase enzymes, principally protein disulphide isomerase (PDI), have emerged as important regulators of platelet function and tissue factor activation via their action on allosteric disulphide bonds. Allosteric disulphides are present in other haemostasis-related proteins, and we have...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.01.034
更新日期:2015-04-01 00:00:00
abstract::This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anes...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0049-3848(01)00316-4
更新日期:2001-08-01 00:00:00
abstract::Human fibrinogen exposed to 46.5 degrees C was subjected to gel permeation chromatography. The protein eluted in two distinct peaks. The first peak appeared in the void volume containing soluble fibrinogen aggregates, while the other peak represented monomeric fibrinogen. In contrast to the monomeric peak material, th...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00063-1
更新日期:1996-04-15 00:00:00
abstract::HC II functional assays are generally preferred with respect to immunochemical assays. Nevertheless functional assays can be biased by the antithrombin III (AT III)-heparin complex activity; in fact trace amounts of heparin generally contaminate dermatan sulfate (DS) commercial preparations used as HC II reaction acti...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90248-9
更新日期:1992-01-15 00:00:00
abstract::Binding of 3H-labeled 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor; PAF) to the intact, washed canine platelet has been defined and characterized as being specific and receptor-mediated. Under the conditions described, specific binding to 2 X 10(7) canine platelets reached saturation with...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(88)90339-8
更新日期:1988-06-15 00:00:00
abstract::The influence of transmembrane Na+ and Ca2+ gradients on cytosolic pH (pHi) and free Ca2+ concentration ([Ca2+]i) have been examined in unstimulated human platelets with the aid of BCECF and Fura-2 fluorescent dyes. The removal of external Na+ (Na+o) acidified the cytosol in a pHo-dependent manner which was insensitiv...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90233-z
更新日期:1992-01-15 00:00:00
abstract::D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample t...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.10.020
更新日期:2007-01-01 00:00:00
abstract::Endothelial cells from human umbilical vein were incubated in vitro with thrombin in the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or dermatan sulfate (DS) to clarify the effect of these glycosaminoglycans on thrombin-stimulated prostaglandin I2 (PGI2) production. Althoug...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90065-k
更新日期:1990-02-15 00:00:00
abstract:BACKGROUND:To investigate the impact of atrial fibrillation/flutter (AF) on adverse in-hospital outcomes in hospitalized surgical patients. METHODS:The nationwide German inpatient sample of the years 2005-2018 was used for this analysis. Surgical patients were stratified by AF and compared. Logistic regression models ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.10.015
更新日期:2020-12-01 00:00:00
abstract::Activation of washed platelets in the presence of EDTA with either 1 U/ml of alpha-thrombin or 2 microM calcium ionophore (A23187) caused the release of one-third to one-half of the platelet factor VIII/von Willebrand factor (FVIII/vWF) into the supernatant. When calcium was present in excess, only 10% of the platelet...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90282-2
更新日期:1984-09-01 00:00:00
abstract::Three methods commonly used for isolation of blood platelets from plasma were compared. Platelets were isolated by: 1) a washing method; 2) a method of metrizamide-gradient centrifugation; 3) a modified method of gel-filtration. The last method employed BSA-Sepharose gel instead of routinely used Sepharose gel saturat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00282-6
更新日期:2000-09-01 00:00:00
abstract::Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either n...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90132-1
更新日期:1989-06-15 00:00:00
abstract::The daily production of billions of platelets must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Complex mechanisms control platelet production and clearance in physiological and pathological conditions. This review will focus on the mechanisms of platelet senescence with specific ...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(16)30370-X
更新日期:2016-05-01 00:00:00
abstract::The fibrinogen molecule consists of two sets of Aalpha, Bbeta, and gamma chains assembled into a bilateral disulfide linked (Aalpha, Bbeta, gamma)2 structure. Cleavage of the two A-fibrinopeptides (FPA, Aalpha1-16) from normal Aalpha chains with arginine at position 16 (RFPA) by thrombin or the venom enzyme atroxin tr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00383-2
更新日期:2001-01-15 00:00:00
abstract::A Ca++-ionophore, ionomycin, increased the volume of human platelets suspended in a Ca++-containing buffer. This change in cell volume was dependent upon ionomycin and extracellular Ca++ concentrations, suggesting that the volume change occurs when the intracellular Ca++ reaches a certain level (greater than uM as det...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90197-k
更新日期:1990-01-01 00:00:00
abstract:INTRODUCTION:The use of oral anticoagulant therapy is increasing in children. Managing anticoagulant therapy in children presents unique challenges, including poor venous access. The advent of point-of-care (POC) monitoring of anticoagulant therapy offers a potential solution to this challenge. This paper reviews the p...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析
doi:10.1016/j.thromres.2005.03.008
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Thrombin or tryptase cleavage of protease-activated receptors (PAR) on human coronary artery endothelial cells (HCAEC) results in activation of a membrane-associated, calcium-independent phospholipase A2 (iPLA2) that selectively hydrolyzes plasmalogen phospholipids. Atherosclerotic plaque rupture results i...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.11.007
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVE:To explore the functional exercises of deep breathing and lower limb motions for the prevention of venous thrombosis in patients undergoing major surgery for gynecologic malignancy. METHODS:All eligible patients admitted to the gynecologic oncology unit were randomized into the study and control groups. A co...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2019.04.013
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Anticoagulated patients are often seen unnecessarily in the emergency department (ED) for epistaxis, leading to increased healthcare costs. Patients are often unaware of preventative and management techniques for handling epistaxis in the home. METHODS:In 2016, the Michigan Anticoagulation Quality Improveme...
journal_title:Thrombosis research
pub_type: 信件
doi:10.1016/j.thromres.2021.01.007
更新日期:2021-01-16 00:00:00
abstract:BACKGROUND:Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.06.027
更新日期:2017-09-01 00:00:00
abstract::The effect of suloctidil (600 mg/day) on platelet survival time (PST) and plasma and urine betathromboglobulin (BTG) was studied in a double-blind, placebo-controlled six-week crossover trial in 13 patients with shortened PST (less than 110 hrs, exponential model). Mean PST after suloctidil (110.6 hrs) was significant...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/0049-3848(84)90231-7
更新日期:1984-08-15 00:00:00
abstract::Two types of LMW heparin were prepared by gel filtration of standard heparin (LMW fraction) and by degradation of heparin by nitrous acid (LMW fragment), respectively. The effects on factor Xa inhibition (XaI), APTT, platelet aggregation and AT III level of these preparations were studied after subcutaneous administra...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90091-9
更新日期:1983-11-15 00:00:00
abstract::The pharmacodynamic and pharmacokinetic properties of endpoint-attached N'alkylamine derivatives of low molecular mass heparin (LMMH), low molecular mass heparin (LMMH), low molecular mass heparin-tyramine (LMMH-tyr) and low molecular mass heparin-tyramine-fluorescein-5-isothiocyanate (LMMH-tyr-fitc) were investigated...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(95)00172-n
更新日期:1995-11-01 00:00:00
abstract::The Calibrated Automated Thrombogram (CAT), a plate-based assay that measures thrombin generation and inhibition in plasma samples, is modified to measure the procoagulant activity of phospholipid associated with plasma microparticles (MP). The assay uses a tissue factor trigger without addition of 4 μM exogenous phos...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.10.018
更新日期:2011-01-01 00:00:00
abstract::An in vitro test system was developed to examine the effects of red blood cells (RBC) on shear-induced platelet adhesion (SIPAD) and platelet aggregation (SIPAG). Suspensions of human platelets labeled with Mepacrine and suspended in citrated plasma were exposed to single, continuous or repetitive (120-300x) one secon...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(98)00160-1
更新日期:1998-12-15 00:00:00