Search results for " Thrombin"
showing 10 items of 17 documents
Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II)
2010
SummaryThis trial compared the efficacy and safety of oral dabigatran, a direct thrombin inhibitor, versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. A total of 2,055 patients were randomised to 28–35 days treatment with oral dabigatran, 220 mg once-daily, starting with a half-dose 1–4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery. The primary efficacy outcome was a composite of total venous thromboembolism [VTE] (venographic or symptomatic) and death from all-causes. The main secondary composite outcome was major VTE (proximal deep-vein thrombosis or non-fatal pulmonary embol…
Argatroban for elective percutaneous coronary intervention: The ARG-E04 multi-center study
2011
The synthetic arginine-derived direct thrombin inhibitor argatroban is an attractive anticoagulant for percutaneous coronary intervention (PCI), because of its rapid onset and offset, and its hepatic elimination. Argatroban was approved for PCI in patients with heparin-induced thrombocytopenia (HIT). However, there are limited data about argatroban in non-HIT patients. The objective of this open-label, multiple-dose, controlled study was to examine the safety and efficacy of argatroban in patients undergoing elective PCI.Of 140 patients randomized to three argatroban dose groups (ARG250, ARG300, and ARG350 with 250, 300, or 350 μg/kg bolus, followed by 15, 20, or 25 μg/kg/min infusion) and …
Anticoagulation with argatroban for elective percutaneous coronary intervention: population pharmacokinetics and pharmacokinetic-pharmacodynamic rela…
2010
The synthetic direct thrombin inhibitor argatroban has a rapid onset and offset of anticoagulation. However, there are no data about the pharmacokinetic-pharmacodynamic (PK-PD) relationship of argatroban in patients undergoing contemporary percutaneous coronary intervention (PCI) and no data about other coagulation parameters than activated clotting time (ACT) in this setting. In the ARG-E04-trial, 140 patients were randomly assigned to argatroban (250, 300, or 350 μg/kg as bolus before PCI, followed by 15, 20, or 25 μg/kg/min infusion) or unfractionated heparin (70-100 IU/kg bolus). A 2-compartment model with first-order elimination adequately described the pharmacokinetic profile of argat…
Antivitamin K Drugs in Stroke Prevention
2014
Among the different subtypes of ischaemic strokes, almost 20 % are of cardiac origin. Different are the causes of cardioembolic stroke, but the most common is the atrial fibrillation, a supraventricular arrhythmia. Appropriate use of antiplatelet drugs and anticoagulants after transient ischaemic attack (TIA) or ischaemic stroke depends on whether the underlying cause is cardioembolic or of presumed arterial origin. Adequate antiplatelet therapy is recommended for secondary prevention after cerebral ischaemia of presumed arterial origin, whether for patients with TIA and ischaemic stroke of cardiac origin, mainly due to atrial fibrillation. Vitamin K antagonists (VKAs) are highly effective …
Signal transduction pathways involved in the mechanical responses to protease-activated receptors in rat colon.
2002
Recording simultaneously in vitro the changes of endoluminal pressure (index of circular muscle activity) and isometric tension (index of longitudinal muscle activity), we examined the mechanisms responsible for the apamin-sensitive relaxant and contractile responses induced by protease-activated receptor (PAR)-1 and PAR-2 activating peptides, SFLLRN-NH2 and SLIGRL-NH2, respectively, in rat colon. In the circular muscle, the inhibitory effects of SFLLRN-NH2 and SLIGRL-NH2 were significantly reduced by ryanodine, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, but unaffected by 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122), a phosph…
THE ROLE OF THROMBIN IN CENTRAL NERVOUS SYSTEM ACTIVITY AND STROKE
2018
Background. Thrombin is a key factor of hemostasis, mediating the conversion of fibrinogen into fibrin. Along with prothrombin, of which thrombin is the active derivative, it has been found locally expressed in the central nervous system. This article aims to describe the role of thrombin in the normal functioning of the central nervous system and stroke.Methods. In this mini-review, the specialized databases Medscape, PubMed, and Web of Science, from the years 2003-2018, were used to find relevant documents by using MeSH terms: ”thrombin” and ”stroke”.Results. Prothrombin and thrombin influence neural development, protection and regeneration, thrombin being a relatively strong regulating f…
Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged Athletes
2018
AbstractSince the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle-distance endurance running on blood coagulation parameters in middle-aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area…
Coagulation and fibrosis in chronic liver disease.
2008
In the hepatic tissue repair mechanism, hepatic stellate cells (HSCs) are recruited at the site of injury and their changes reflect paracrine stimulation by all neighbouring cell types, including sinusoidal endothelial cells, Kupffer cells, hepatocytes, platelets and leucocytes. Thrombin converts circulating fibrinogen to fibrin, promotes platelet aggregation, is a potent activator of endothelial cells, acts as a chemoattractant for inflammatory cells and is a mitogen and chemoattractant for fibroblasts and vascular smooth muscle cells. Most of the cellular effects elicited by thrombin are mediated via a family of widely expressed G-protein-coupled receptors termed protease activated recept…
Prothrombinase-Induced Clotting Time Assay for Determination of the Anticoagulant Effects of Unfractionated and Low-Molecular-Weight Heparins, Fondap…
2008
The prothrombinase-induced clotting time assay (PiCT, Pentapharm, Basel, Switzerland) is a clotting assay sensitive to factor Xa and factor IIa inhibitors. It is based on the addition of factor Xa and snake venom RVV-V (Russell viper venom factor V activator) specifically activating factor V and phospholipids to platelet-poor plasma. Following an incubation time, the mixture is recalcified and the clotting time is determined. An almost linear dose-response and high sensitivity of the assay for unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), r-hirudin, and argatroban was found. Fondaparinux showed a nonlinear dose-response. By using ex vivo samples, the following Pearson…
Interaction of inflammation, thrombosis, aspirin and enoxaparin in CNS experimental antiphospholipid syndrome
2008
Experimental antiphospholipid syndrome (eAPS) induced by immunization with beta(2)-glycoprotein I (beta(2)-GPI) causes behavioral hyperactivity. We assessed the role of thrombotic and inflammatory perivascular factors and standard APS therapies for CNS manifestations. Groups of mice (n=10 per group) were immunized once with beta(2)-GPI (eAPS) or adjuvant (controls) and treated daily from 1 month after immunization with either sham injections, aspirin (1.2 mg/kg) or enoxaparin (1 mg/kg) for 3 months. Serum antiphospholipid antibodies (aPL) and brain levels of tissue necrosis factor-alpha (TNF-alpha) and prostaglandin E (PGE) were then measured by ELISA and thrombin inhibitors by immunoblot. …