View clinical trials related to Fibrinolysis.
Filter by:Background. Consensus is lacking regarding the use of tranexamic acid (TXA) in calcaneal fracture surgery. This study aims to investigate the hypothesis that local infiltration of TXA in the post-operation would maintain hemoglobin (Hb) level, reduce incision drainage volume and risk of infection in patients with displaced intra-articular calcaneal fractures. Methods. A total of 120 patients with displaced intra-articular calcaneal fractures who received extensible lateral L-shaped approach were included in this trial and equally randomized to receive one single dose of 1g TXA or 1g normal saline after closing incision. The demographic data and fracture characteristics, intra-operative indicators, laboratory tests and Visual Analogue Scale (VAS) scores, incision drainage volume, and incision-related complications were collected and compared between the two groups.
Up to 15% of operations in cardio-pulmonary by-pass are complicated by excessive postoperative blood loss, which negatively affects the outcomes. Recently, it has been demonstrated that fibrin clot susceptibility to lysis is a modulator of postoperative blood loss after cardiac surgery for aortic stenosis. Earlier, a preliminary study showed a negative association of postoperative blood loss after coronary artery by-pass grafting (CABG) with fibrin clot lysis time, reflecting susceptibility to fibrinolysis. In CABG, postoperative blood loss may depend on the operative technique with respect to left internal mammary artery (LIMA) harvesting. LIMA is taken down in virtually all CABG procedures, but harvesting technical details remain at surgeons discretion (skeletonization without opening the pleural cavity vs. pedicled graft with pleura wide open). The investigators decided to test the hypothesis that fibrin clot properties modulate the postoperative drainage following CABG strongly enough to attenuate the influence of surgical technique by randomizing the patients undergoing CABG with regard to LIMA harvesting technique.
Lysine analogs, like tranexamic acid (TXA) or epsilon aminocaproic acid (EACA), are antifibrinolytic agents routinely administered in children undergoing different surgeries associated with a high bleeding risk (e.g. cardiac, craniofacial, and orthopedic surgeries). Although there is a growing literature regarding the pharmacokinetic characteristics of these drugs in children, the plasmatic concentration required to completely inhibit fibrinolysis remains to be determined. In this in vitro study, the investigators will use an experimental model of fibrinolysis designed for rotational thromboelastometry (ROTEM®) to determine the minimal concentration inhibiting fibrinolysis for both TXA and EACA. In addition, this study will be used to create and validate a new experimental assay to measure fibrinolysis and the effect of antifibrinolytic agents.
This is a two-center, prospective, randomized, single-blind, investigator initiated, pharmacodynamic study of parallel design, carried out in 2 PCI-capable cardiology centers (Patras University Hospital and Konstantopoulio General Hospital of Athens). Patients with ST elevation myocardial infarction, having undergone fibrinolysis in the previous 3 to 48 hours, who present high residual PR (defined as PRU ≥208 ) on admission, pre coronary angiography, will be randomized after written informed consent, in a 1:1 ratio to either: Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD, until discharge. Or Clopidogrel 600mg loading dose (LD), followed by a 150mg once daily maintenance dose (MD) starting 12±6 hours post LD, until discharge. Platelet reactivity assessment will be performed at randomization (Hour 0) and at 2, 24 hours after randomization, as well as pre-discharge, using the VerifyNow assay, in platelet reactivity units (PRU). Documentation of major adverse cardiac events (death, myocardial infarction, stroke, ischemia driven revascularization procedure with PCI or CABG) and bleeding (according to BARC criteria) will be performed until patient's discharge.
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary bypass (CPB).1 CPB is associated with significant morbidity including hemodynamic instability, the transfusion of allogenic blood products, and inflammation. Blood product transfusion increases mortality after cardiac surgery. Enhanced fibrinolysis contributes to increased blood product transfusion requirements in the perioperative period. CPB activates the kallikrein-kinin system (KKS), leading to increased bradykinin concentrations. Bradykinin, acting through its B2 receptor, stimulates the release of nitric oxide, inflammatory cytokines and tissue-type plasminogen activator (t-PA). Based on data indicating that angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with coronary artery disease, many patients undergoing CPB are taking ACE inhibitors. While interruption of the renin-angiotensin system (RAS) reduces inflammation in response to CPB, ACE inhibitors also potentiate the effects of bradykinin and may augment B2-mediated change in fibrinolytic balance and inflammation. In contrast, angiotensin II type 1 receptor antagonism does not potentiate bradykinin and does not inhibit bradykinin metabolism. Studies in animals suggest that bradykinin receptor antagonism inhibits reperfusion-induced increases in vascular permeability and neutrophil recruitment.A randomized, placebo controlled clinical trial of a bradykinin B2 receptor antagonist demonstrated some effect on survival in patients with systemic inflammatory response syndrome and gram-negative sepsis. In addition, we and others have shown bradykinin B2 receptor antagonism reduces vascular t-PA release during ACE inhibition. The current proposal derives from data from our laboratory and others elucidating the role of the KKS in the inflammatory, hypotensive and fibrinolytic response to CPB. Specifically, we have found that CPB activates the KKS and that ACE inhibition and smoking further increases bradykinin concentrations. During CPB, bradykinin concentrations correlate inversely with mean arterial pressure and directly with t-PA. Moreover, we have found that bradykinin receptor antagonism attenuates protamine-related hypotension following CPB. The current proposal tests the central hypothesis that the fibrinolytic and inflammatory response to cardiopulmonary bypass differ during angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism.
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary bypass (CPB). CPB is associated with significant morbidity including the transfusion of allogenic blood products, inflammation and hemodynamic instability. In fact, approximately 20% of all blood products transfused are associated with coronary artery bypass grafting procedures. Transfusion of allogenic blood products is associated with well-documented morbidity and increased mortality after cardiac surgery. Enhanced fibrinolysis contributes to increased blood product transfusion in the perioperative period. The current proposal tests the central hypothesis that endogenous bradykinin contributes to the hemodynamic, fibrinolytic and inflammatory response to CPB and that bradykinin receptor antagonism will reduce hypotension, inflammation and transfusion requirements. In SPECIFIC AIM 1 we will test the hypothesis that the fibrinolytic and inflammatory response to CPB differ during ACE inhibition and angiotensin II type 1 receptor antagonism. In SPECIFIC AIM 2 we will test the hypothesis that bradykinin B2 receptor antagonism attenuates the hemodynamic, fibrinolytic, and inflammatory response to CPB. In SPECIFIC AIM 3 we will test the hypothesis that bradykinin B2 receptor antagonism reduces the risk of allogenic blood product transfusion in patients undergoing CPB. These studies promise to provide important information regarding the effects of drugs that interrupt the RAS and generate new strategies to reduce morbidity in patients undergoing CPB.