Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the antithrombotic therapies evaluated to date, the synthetic peptide bivalirudin is unique in its ability to reduce both ischemic and bleeding complications associated with percutaneous coronary intervention (PCI). Bivalirudin is a small peptide consisting of 20 amino acid residues that binds thrombin in a direct, reversible, and bivalent fashion. The agent is approved for use in the United States and New Zealand as an anticoagulant in patients with unstable angina undergoing PCI and may also prove beneficial in patients with acute coronary syndromes (ACS), acute myocardial infarction (AMI) and in patients undergoing coronary artery bypass graft (CABG) procedures. This article examines bivalirudin in more detail.
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PMID:Bivalirudin, a bivalent, thrombin specific anticoagulant as an alternative to heparin in interventional procedures as an alternative to heparin in interventional procedures. 1221 63

An 81-year-old man with previous syncopal episodes, progressive shortness of breath, pulmonary edema, severe calcific aortic stenosis, and a history of heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin, a thrombin-specific anticoagulant, was used in place of heparin. The patient received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was readily obtained resulting in an uneventful cardiopulmonary bypass. Activated clotting time (ACT) values steadily declined after discontinuation of the bivalirudin infusion. Bivalirudin is a practical alternative to heparin during cardiac surgical procedures.
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PMID:Favorable outcome with bivalirudin anticoagulation during cardiopulmonary bypass. 1253 26

We describe two cases of intracoronary vascular brachytherapy where bivalirudin (Angiomax), employed as an anticoagulant, led to abrupt vessel closure or threatened abrupt closure. Use of bivalirudin (Angiomax) during intracoronary brachytherapy may predispose to the formation of intracoronary thrombus, related to the reversible binding kinetics of the bivalirudin to thrombin, and resulting in recovery of thrombin functional activity during periods of prolonged stasis that occur during intracoronary brachytherapy. Intracoronary abciximab administration may be a useful strategy in resolving the acute closure, since abciximab administered early during the formation of thrombus has been shown to facilitate clot lysis.
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PMID:Bivalirudin (Angiomax) use during intracoronary brachytherapy may predispose to acute closure. 1265 25

Thrombin-specific inhibitors directly diminish thrombin-induced coagulation and cellular activities without the side effects of heparin. Hirudin is the most potent natural thrombin-specific inhibitor. Recombinant hirudins (such as desirudin) have been shown to be effective in the treatment of heparin-induced thrombocytopenia (HIT) and in the prevention of thrombotic complications after hip or knee surgery. The application of recombinant hirudin has been limited mainly by hemorrhagic complications. Synthetic thrombin-specific inhibitors, including oligopeptides, tripeptides and non-peptide low molecular weight (LMW) thrombin inhibitors, have been designed according to their interactions with the active sites of thrombin. Bivalirudin (an anti-thrombin oligopeptide) has been approved for preventing thrombosis in unstable angina patients following angioplasty in adjunct to aspirin. Argotroban (a tripeptide thrombin inhibitor) has been used for the treatment of HIT, peripheral and cerebral thrombotic diseases. The benefit of using thrombin-specific inhibitors alone in acute myocardial infarction or unstable angina remains uncertain. A number of LMW thrombin-specific inhibitors have been developed. Some of them can be administrated orally, and cause less increase in bleeding time than other thrombin inhibitors. The efficacy, safety, stability and oral bioavailability of the thrombin inhibitors may be considerably improved through structural optimization. Most of the LMW thrombin inhibitors are currently being tested in animal models or at early stages of clinical trials. In this review, we will present an overview of recent advances in thrombin-specific inhibitors.
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PMID:Development and current applications of thrombin-specific inhibitors. 1276 63

With advances in therapy of acute coronary syndromes, repetitive exposure to heparin has become commonplace. Consequently, the incidence of heparin-induced thrombocytopenia has risen. Limited strategies for management exist, and new thrombin inhibitors may provide safe alternatives to heparin. Two patients with documented heparin-induced thrombocytopenia underwent revascularization using a new thrombin inhibitor (Bivalirudin [Angiomax, Medicines Co, Cambridge, MA]) for anticoagulation. Both patients had uneventful perioperative hospitalizations. Thrombin inhibition with Bivalirudin (Angiomax) may provide a safe reliable alternative to heparin use in cardiac surgery [corrected].
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PMID:Bivalirudin use in off-pump myocardial revascularization in patients with heparin-induced thrombocytopenia [corrected]. 1284 58

The chemistry and pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, dosing and administration, and pharmacoeconomics of bivalirudin are reviewed; clinical trials of bivalirudin's application in percutaneous coronary intervention (PCI) are also discussed. Bivalirudin is a direct thrombin inhibitor approved for use in PCI. It reversibly binds to thrombin's catalytic site and substrate recognition site and blocks both circulating and fibrin-bound thrombin. Peak concentrations occur in less than 5 minutes after bolus-dose administration, and its half-life is approximately 25 minutes. It is primarily eliminated renally, and dosage reduction may be required in patients with severe renal dysfunction. Two clinical trials have demonstrated that bivalirudin is at least as effective as unfractionated heparin (UFH) in preventing ischemic complications in PCI. Other trials have shown that bivalirudin has beneficial ischemic and hemorrhagic outcomes in a more modern PCI setting (i.e., intracoronary stent placement, clopidogrel, and glycoprotein IIb/IIIa-receptor inhibitors). Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors was noninferior to UFH with planned glycoprotein IIb/IIIa inhibitors and superior to UFH alone with respect to ischemic and hemorrhagic endopoints in PCI. Major bleeding with bivalirudin has occurred in approximately 3% of patients in clinical trials, and it is not known to have any interactions with the cytochrome P-450 isoenzyme system. The acquisition cost of bivalirudin in one study was less than the combination of UFH and glycoprotein IIb/IIIa inhibitors. Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors appears to be an acceptable alternative to the standard of care and is superior to UFH alone in PCI.
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PMID:Bivalirudin in percutaneous coronary intervention. 1452 Oct 34

Thrombin is a pivotal molecule in acute myocardial infarction (MI) because of its extensive procoagulant and prothrombotic actions. Antithrombin therapy is an important component of the pharmacotherapy for acute MI. The standard agent used in clinical practice, unfractionated heparin (UFH), is associated with the disadvantages of variable anticoagulant effect, inability to inhibit clot-bound thrombin, neutralization by platelet factor 4, and the propensity to cause thrombocytopenic complications. Novel thrombin inhibitors have been developed to overcome these disadvantages. Although possessing the property of inhibiting both fluid-phase and clot-bound thrombin, the direct thrombin inhibitor hirudin has been shown to give marginal benefits over UFH as adjunct to fibrinolysis in ST-elevation MI. Bivalirudin, another direct thrombin inhibitor, is able to reduce reinfarction in patients treated with streptokinase and is a new anticoagulant treatment option in this setting. The pharmacokinetic characteristics of better availability, longer half-life, and dose-independent clearance together with the ability of inhibiting both thrombin generation and activity make the low-molecular-weight heparins (LMWHs) an attractive alternative to UFH. The favorable benefit/risk profile of the LMWHs as adjunct to different generations of fibrinolytic agents is setting the stage for larger clinical trials to confirm their role as the antithrombin agent of choice for STEMI.
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PMID:Advances in antithrombin therapy for ST-elevation myocardial infarction. 1464 54

Bivalirudin is being used more frequently as an anticoagulant in the cardiac catheterization laboratory. Newer devices, used to measure activated clotting time (ACT), have not been thoroughly tested for use with bivalirudin. One such device, the i-STAT ACT, measures the generation of activated thrombin to determine the level of anticoagulation. Our study demonstrated a high level of agreement between the i-STAT ACT and the Hemochron ACT in patients anticoagulated with bivalirudin. In addition, the i-STAT was shown to have an extremely high degree of reproducibility.
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PMID:Validation of the i-STAT handheld activated clotting time for use with bivalirudin. 1513 17

Coronary artery thrombosis is usually triggered by platelet-rich thrombus superimposed on a spontaneously or mechanically disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Unfractionated heparin and aspirin have served as cornerstones in the prevention and treatment of intracoronary thrombus, but unfractionated heparin has several limitations that necessitate the use of adjunctive therapies, such as glycoprotein IIb/IIIa receptor inhibitors and clopidogrel, in order to reduce the risk of ischemic events. These combination therapies, however, typically increase the risk for bleeding complications, as well as the cost and complexity of treatment. Bivalirudin (Angiomax, The Medicines Company), a thrombin-specific anticoagulant, does not share heparin's limitations. Bivalirudin appears to provide clinical advantages over unfractionated heparin therapy in acute coronary syndrome patients and those undergoing percutaneous coronary intervention, without increasing cost or complexity of treatment for most patients.
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PMID:Bivalirudin: an anticoagulant option for percutaneous coronary intervention. 1515 64

Thromboembolic complications are increasing in children, and the use of anticoagulation has seen a dramatic increase despite the lack of randomized clinical trials. The most widely used agents in children are heparin and warfarin, however these agents have limitations that are exaggerated in children. This has led to the use of newer agents with improved pharmacologic properties such as low-molecular-weight heparin, however, the use of novel agents such as direct thrombin inhibitors has been limited to case reports. These agents, however, have potential advantages over heparin, low-molecular-weight heparin and warfarin. Current clinical trials are in progress to define the proper dose of two such agents--argatroban (Argatroban, GlaxoSmithKline) and bivalirudin (Angiomax, The Medicines Company). The selective Factor Xa inhibitor fondaparinux (Arixtra, Sanofi-Synthelabo) has not been used in children; however, there are situations in which this agent may be advantageous. This review will discuss the currently available agents, with an emphasis on those that are novel and their potential uses in children.
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PMID:Current and future antithrombotic agents in children. 1522 12


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