Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Feb 2015
Randomized Controlled TrialProfound endothelial damage predicts impending organ failure and death in sepsis.
Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. ⋯ Profound damage to the endothelium independently predicts risk of multiple organ failure and death in septic patients. Our findings also suggest that the detrimental effect of profound endothelial damage on risk of death operates via mechanisms other than causing organ failures per se. Therefore, damage to the endothelium appears centrally involved in the pathogenesis of death in sepsis and could be a target for intervention.
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Semin. Thromb. Hemost. · Feb 2014
Randomized Controlled Trial Multicenter StudyDevelopment of a tool to identify patients' preference for vitamin K antagonist or direct oral anticoagulant therapy.
Direct oral anticoagulants (DOACs) were developed for the treatment of thromboembolic diseases to overcome limitations of vitamin K antagonists (VKA). International guidelines on atrial fibrillation acknowledge patients' for antiembolic therapy with VKA or DOAC as relevant decision criteria. The objective assessment of patients' preference social interactions and psychological factors are hard to measure albeit representing important contributors. ⋯ Indication for anticoagulation were atrial fibrillation (n = 106), pulmonary embolism (n = 24), deep vein thrombosis (n = 40), artificial heart valve replacement (n = 8), or other diseases (n = 2). Based on the results of the analysis, a score will be suggested to identify the preference of patients for anticoagulation with VKA or DOAC. This tool may be useful for practitioners and health-care professionals to support patient adherence to therapy, and thereby increase treatment effectiveness.
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Semin. Thromb. Hemost. · Jun 2004
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialBivalirudin in PCI: an overview of the REPLACE-2 trial.
The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. ⋯ There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.
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Semin. Thromb. Hemost. · Jun 2004
Review Randomized Controlled Trial Clinical TrialRecombinant platelet factor 4 for heparin neutralization.
Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the alpha granules of platelets for later release. Although the complete physiologic role of PF4 is unknown, it is highly effective for the neutralization of heparin anticoagulation. ⋯ Serial measurements of rPF4 levels showed a monophasic elimination pattern with a serum half-life of 25.5 +/- 13.5 minutes that was independent of dose administered. A randomized and blinded trial comparing rPF4 to protamine confirmed the safety and effectiveness of rPF4. Although rPF4 was initially being evaluated as a clinical alternative to protamine, it is not currently being developed for general clinical use.
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Semin. Thromb. Hemost. · Jun 2004
Randomized Controlled Trial Clinical TrialBivalirudin, blood loss, and graft patency in coronary artery bypass surgery.
A safe and effective alternative is needed for patients in whom unfractionated heparin (UFH) or protamine is contraindicated (e.g., those with heparin-induced thrombocytopenia or allergy to protamine). Furthermore, choice of anticoagulant may influence graft patency in coronary surgery and may therefore be important even when there is no contraindication to UFH. Direct thrombin inhibitors have several potential advantages over UFH, demonstrated in acute coronary syndromes. ⋯ Median graft flow was significantly higher in the bivalirudin group. We concluded that anticoagulation for OPCAB surgery with bivalirudin was feasible without a clinically important increase in perioperative blood loss. A larger study is needed to investigate the impact of improved graft patency on other clinical outcomes after cardiac surgery.