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Direct Thrombin Inhibitor

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1. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis. (PubMed)

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis. Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel (...) oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT.To assess the effectiveness of oral DTIs and oral factor Xa

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2015 Cochrane

2. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism. (PubMed)

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism. Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral (...) factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism.To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment

2015 Cochrane

3. Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation. (PubMed)

Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation. Chronic anticoagulation with vitamin K antagonists (VKAs) prevents ischaemic stroke and systemic embolism in people with non-valvular atrial fibrillation (AF) but dose adjustment, coagulation monitoring and bleeding limits its use. Direct thrombin inhibitors (DTIs) are under investigation as potential alternatives.To assess (1) the comparative

2014 Cochrane

4. Interruption in Use of the New Class of Direct Thrombin Inhibitors and Factor Xa Inhibitors is Not Indicated for the Anticoagulated Patient Undergoing Simple Dental Procedures

Interruption in Use of the New Class of Direct Thrombin Inhibitors and Factor Xa Inhibitors is Not Indicated for the Anticoagulated Patient Undergoing Simple Dental Procedures UTCAT2828, Found CAT view, CRITICALLY APPRAISED TOPICs University: | | ORAL HEALTH EVIDENCE-BASED PRACTICE PROGRAM View the CAT / Title Interruption in Use of the New Class of Direct Thrombin Inhibitors and Factor Xa Inhibitors is Not Indicated for the Anticoagulated Patient Undergoing Simple Dental Procedures Clinical (...) prior to suspension of the medication regimen prior to invasive surgery. Eliquis (apixaban) and Savaysa (edoxaban) are recently approved factor Xa inhibitors that have similar properties to Xarelto and Pradaxa but were not specifically discussed here. Specialty/Discipline (General Dentistry) (Oral Surgery) Keywords rivaroxaban, dabigatran, oral anticoagulants, xarelto, pradaxa ID# 2828 Date of submission: 03/27/2015 E-mail harrisonce@livemail.uthscsa.edu Author Craig Harrison Co-author(s) Co-author

2015 UTHSCSA Dental School CAT Library

5. The Direct Thrombin Inhibitors Dabigatran and Lepirudin Inhibit GPIbα-Mediated Platelet Aggregation. (PubMed)

The Direct Thrombin Inhibitors Dabigatran and Lepirudin Inhibit GPIbα-Mediated Platelet Aggregation. The direct thrombin inhibitor (DTI) dabigatran is a non-vitamin K antagonist oral anticoagulant for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. In addition to its anti-thrombotic efficacy, dabigatran has been suggested to exert some pro-thrombotic effect due to fostering the ligation of thrombin to its high affinity platelet receptor (...) occurring during echicetin-induced platelet aggregation), but did not inhibit adenosine diphosphate- or thromboxane A2-induced platelet aggregation. Thrombin was not generated in response to ristocetin/vWF or echicetin beads and therefore did not explain the inhibitory effect of the DTIs. Therapeutic concentration of lepirudin and dabigatran did not affect significantly platelet vasodilator-stimulated phosphoprotein S239 phosphorylation or cGMP and cyclic adenosine monophosphate levels. These data

2019 Thrombosis and haemostasis

6. Factor Xa Inhibitors and Direct Thrombin Inhibitors Versus Low-Molecular-Weight Heparin for Thromboprophylaxis After Total Hip or Total Knee Arthroplasty: A Systematic Review and Meta-Analysis. (PubMed)

Factor Xa Inhibitors and Direct Thrombin Inhibitors Versus Low-Molecular-Weight Heparin for Thromboprophylaxis After Total Hip or Total Knee Arthroplasty: A Systematic Review and Meta-Analysis. The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA).MEDLINE, Cochrane, EMBASE, and Google Scholar (...) databases were searched until June 30, 2017 for eligible randomized controlled studies.Thirty-two randomized controlled studies were included. LMWH provided better protection against VTE than placebo. In both TKA and THA patients, the rates of VTE were lower with factor Xa inhibitors than LMWH. In THA patients, the rate of deep vein thrombosis (DVT) was lower with factor Xa inhibitors than LMWH. In TKA patients, the rates of VTE and DVT were similar between LMWH and direct thrombin inhibitors. In THA

2018 Journal of Arthroplasty

7. Assessment of in vitro effects of direct thrombin inhibitors and activated factor X inhibitors through clot waveform analysis. (PubMed)

Assessment of in vitro effects of direct thrombin inhibitors and activated factor X inhibitors through clot waveform analysis. Clot waveform analysis (CWA) has been reported to extend the interpretation of clotting time measurement. The parameters obtained from successive derivatives of the clotting reaction curves reflect the rates of activation of individual coagulation factors, theoretically dissecting the cascade pathway. This study aims to assess the in vitro effects of direct thrombin (...) versus FXa inhibitors.The APTT-CWA demonstrated evidence for the blockade of thrombin-positive feedback by DTIs and FXa inhibitors and that for the differences in anticoagulant cooperativity between them. The results demonstrate the usability of CWA for assessment of anticoagulation and provide insights into direct anticoagulants.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

2018 Journal of Clinical Pathology

8. Comparison of antithrombin‐dependent and direct inhibitors of factor Xa or thrombin on the kinetics and qualitative characteristics of blood clots (PubMed)

Comparison of antithrombin‐dependent and direct inhibitors of factor Xa or thrombin on the kinetics and qualitative characteristics of blood clots Venous thromboembolism (VTE) is associated with significant morbidity and mortality.We investigated the impact of direct and AT-dependent FXa or thrombin inhibitors on thrombus formation.Whole blood thromboelastometry and thrombin generation were assessed after triggering the TF pathway. Clinically relevant concentrations of rivaroxaban (...) was significantly affected only by tinzaparin that also reduced the MCF. The association of rivaroxaban and dabigatran did not affect the MCF, although it amplified the effect on CFT and α-angle.All agents delayed thrombus formation. However, the compounds differed substantially with respect to fibrin polymerization rate and clot firmness. Comparison of the data obtained by thrombin generation assessment with those obtained by the thromboelastometric study shows that the delay in clot formation is principally

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2018 Research and Practice in Thrombosis and Haemostasis

9. Diagnostic Accuracy of a Novel Chromogenic Direct Thrombin Inhibitor Assay: Clinical Experiences for Dabigatran Monitoring. (PubMed)

Diagnostic Accuracy of a Novel Chromogenic Direct Thrombin Inhibitor Assay: Clinical Experiences for Dabigatran Monitoring. Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists (VKA) for clinical indications requiring long-term oral anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran—the only direct thrombin inhibitor amongst them—does not require therapeutic drug monitoring. However, in case of treatment complications (e.g (...) patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with HTI using ultra performance liquid chromatography—tandem mass spectrometry as the reference method for measuring dabigatran plasma concentrations. Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p < 0.0001) as well as a low intra- and inter-assay variation of <5%. Compared with HTI

2017 Thrombosis and haemostasis

10. Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors. (PubMed)

Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors. Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring (...) anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT

2017 Seminars In Thrombosis And Hemostasis

11. Evidence for Idarucizumab (Praxbind) in the Reversal Of the Direct Thrombin Inhibitor Dabigatran: Review Following the RE-VERSE AD Full Cohort Analysis (PubMed)

Evidence for Idarucizumab (Praxbind) in the Reversal Of the Direct Thrombin Inhibitor Dabigatran: Review Following the RE-VERSE AD Full Cohort Analysis Idarucizumab is the first reversal agent approved for the direct thrombin inhibitor dabigatran. The authors summarize the findings from the clinical trial series and describe case reports, post-marketing data, and ongoing studies.

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2017 Pharmacy and Therapeutics

12. Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies (PubMed)

Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies Thrombin acts as a key enzyme in the blood coagulation cascade and represents a potential drug target for the treatment of several cardiovascular diseases. The aim of this study was to identify small-molecule direct thrombin inhibitors from herbs used in traditional Chinese medicine (TCM). A pharmacophore model and molecular docking were utilized (...) to virtually screen a library of chemicals contained in compositions of traditional Chinese herbs, and these analyses were followed by in vitro bioassay validation and binding studies. Berberine (BBR) was first confirmed as a thrombin inhibitor using an enzymatic assay. The BBR IC50 value for thrombin inhibition was 2.92 μM. Direct binding studies using surface plasmon resonance demonstrated that BBR directly interacted with thrombin with a KD value of 16.39 μM. Competitive binding assay indicated that BBR

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2017 Scientific reports

13. Development of bioanalytical assays for variegin, a peptide-based bivalent direct thrombin inhibitor (PubMed)

Development of bioanalytical assays for variegin, a peptide-based bivalent direct thrombin inhibitor Variegin is an anticoagulant peptide that will be tested in porcine models of percutaneous coronary intervention. We developed three bioanalytical assays for variegin quantitation and utilized these methods to evaluate pharmacokinetics of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8 (...) -5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half-lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic assays were 52.3 ± 4.4, 50.4 ± 5.9 and 67.7 ± 6.3 min, respectively.We developed three bioanalytical assays for a novel direct thrombin inhibitor, variegin. The thrombin time assay is optimized for variegin quantitation during future porcine studies and clinical trials.

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2017 Bioanalysis

14. Direct Thrombin Inhibitors Prevent Left Atrial Remodeling Associated With Heart Failure in Rats (PubMed)

Direct Thrombin Inhibitors Prevent Left Atrial Remodeling Associated With Heart Failure in Rats The present study tested the hypothesis that thrombin participates in formation of left atrial remodeling and that direct oral anticoagulants, such as direct thrombin inhibitors (DTIs), can prevent its progression. In a rat model of heart failure associated with left atrial dilation, we found that chronic treatment with DTIs reduces the atrial remodeling and the duration of atrial fibrillation (AF

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2016 JACC: Basic to Translational Science

15. The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation (PubMed)

The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect at the polymer-blood interface. Previous work has (...) demonstrated the potential use of argatroban, a direct thrombin inhibitor, as a nonthrombogenic material for extracorporeal devices. The work reported here focuses on the characterization of argatroban linked to a polyurethane-silicone polymer, CarboSil®. Chemical immobilization, the amount of argatroban, incubation times, and saturation point were evaluated to achieve maximal antithrombin activity at the polymer surface. Cross-linked polymer coatings reacted with 10 and 30 µmole of argatroban were

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2016 Journal of materials chemistry. B, Materials for biology and medicine

16. Direct Thrombin Inhibitor

Direct Thrombin Inhibitor Direct Thrombin Inhibitor Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Direct Thrombin Inhibitor Direct (...) Thrombin Inhibitor Aka: Direct Thrombin Inhibitor , Antithrombin , Hirudin , Lepirudin , Refludan , Bivalirudin , Angiomax , Desirudin , Ipravask , Argatroban , Acova From Related Chapters II. Indications Thrombus prophylaxis, treatment or and III. Dosing: Hirudins (bivalent peptide derivatives from Salivary Gland of medicinal leaches) Lepirudan (Refludan) See other references for dosing Bivalirudin (Angiomax) Used in if contraindicated Coadminister with Initial: 0.75 mg/kg IV bolus Later: 1.75 mg/kg

2018 FP Notebook

17. Direct Thrombin Inhibitor Resistance and Possible Mechanisms (PubMed)

Direct Thrombin Inhibitor Resistance and Possible Mechanisms Objective: To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary: The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate (...) for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT. Indications for bivalirudin were anticoagulation in intra-aortic balloon pump, treatment of deep vein thrombosis, and heparin-induced thrombocytopenia with thrombosis. Target aPTT was achieved between 25.5 and 134 hours after initiation despite appropriate titration intervals per protocol. Discussion: Bivalirudin is a direct thrombin inhibitor frequently used off-label for the medical

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2016 Hospital pharmacy

18. Risk guided use of the direct thrombin inhibitor bivalirudin: insights from recent trials and analyses (PubMed)

Risk guided use of the direct thrombin inhibitor bivalirudin: insights from recent trials and analyses 27747056 2018 11 13 2072-1439 8 9 2016 Sep Journal of thoracic disease J Thorac Dis Risk guided use of the direct thrombin inhibitor bivalirudin: insights from recent trials and analyses. E1034-E1040 Hillegass William B WB Heart South Cardiovascular Group, Brookwood Shelby Baptist Medical Center, Department of Biostatistics, University of Alabama at Birmingham, Alabaster and Birmingham

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2016 Journal of thoracic disease

19. Oral direct thrombin inhibitors versus factor Xa inhibitors in atrial fibrillation patients undergoing ablation: a meta-analysis

Oral direct thrombin inhibitors versus factor Xa inhibitors in atrial fibrillation patients undergoing ablation: a meta-analysis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne

2019 PROSPERO

20. Identification of a Thrombomodulin Interaction Site on Thrombin Activatable Fibrinolysis Inhibitor that Mediates Accelerated Activation by Thrombin. (PubMed)

Identification of a Thrombomodulin Interaction Site on Thrombin Activatable Fibrinolysis Inhibitor that Mediates Accelerated Activation by Thrombin. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a human plasma zymogen that provides a molecular connection between coagulation and fibrinolysis. TAFI is activated through proteolytic cleavage by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin (TM) or plasmin. Evidence from several studies suggests that TM (...) and TAFI make direct contact at sites remote from the activating cleavage site to facilitate acceleration of thrombin-mediated TAFI activation. The elements of TAFI structure that allow accelerated activation of thrombin by TM are incompletely defined.To identify TM interaction regions on TAFI that mediate acceleration of activation by thrombin and therefore indicate TM binding sites on TAFI.We mutated selected surface-exposed charged residues on TAFI to alanine in order to identify sites that mediate

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2016 Journal of Thrombosis and Haemostasis

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