Platelet-sparing properties of aprotinin: A scoping review on mechanisms and clinical effects. Cardiac surgery involving cardiopulmonary bypass (CPB) is associated with the risk of acquired coagulopathy, including dysregulated fibrinolysis, which can result in life-threatening bleeding complications. Aprotinin, an antifibrinolytic agent, has been recommended for the prevention of these complications. Its effectiveness has been attributed to its ability to nonspecifically inhibit various serine proteases involved in the coagulation and fibrinolysis cascade. Additionally, aprotinin may protect platelets from CPB-induced dysfunction through a platelet-sparing effect, further enhancing its efficacy. The biochemical pathways underlying aprotinin's platelet-sparing effect remain unclear
Use of Aprotinin versus Tranexamic Acid in Cardiac Surgery Patients with High-Risk for Excessive Bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study. Following the reintroduction of aprotinin into the European market, the French Society of Cardiovascular and Thoracic Anaesthesiologists recommended its prophylactic use at half-dose for high-risk cardiac surgery patients. We examined whether the use of aprotinin instead of tranexamic acid could significantly reduce severe perioperative bleeding. This multicentre, retrospective, historical study included cardiac surgery patients treated with aprotinin or tranexamic acid between December 2017 and September 2020. The primary efficacy end point was the severe or massive perioperative bleeding (class
Ulinastatin in combination with aprotinin improves systemic inflammation in patients undergoing cardiac surgery with cardiopulmonary bypass. To investigate the impact of ulinastatin combined with protease inhibitors on serum inflammatory factors in patients undergoing cardiac surgery with cardiopulmonary bypass. A retrospective analysis was conducted on 86 patients who underwent cardiac surgery
Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19 SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system. This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length
Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study. Thromboinflammation plays a central role in severe COVID-19. The kallikrein pathway activates both inflammatory pathways and contact-mediated coagulation. We investigated if modulation of the thromboinflammatory response improves outcomes in hospitalized COVID-19 patients. In this multicenter open-label randomized clinical trial (EudraCT 2020-001739-28), patients hospitalized with COVID-19 were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention. The intervention consisted of aprotinin (2,000,000 IE IV four times daily) combined with low molecular weight heparin (LMWH; SC 50 IU/kg twice daily on the ward, 75 IU/kg
Safety and efficacy of aprotinin versus tranexamic acid for reducing absolute blood loss and transfusion in pediatric patients undergoing craniosynostosis surgery: a randomized, double-blind, three-arm controlled trial. Craniosynostosis surgery is associated with considerable blood loss and need for transfusion. Considering the lower estimated blood volume (EBV) of children compared to adults , excessive blood loss may quickly lead to hypovolemic shock. Therefore, reducing blood loss is important in craniosynostosis surgery. This study was conducted to evaluate the efficacy of aprotinin or tranexamic acid (TXA) in blood loss reduction in these patients. In the current randomized controlled trial, 90 eligible pediatric patients with craniosynostosis were randomly divided into three groups
Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery. Aprotinin has been used to reduce blood loss and blood product transfusions in patients at high risk of major blood loss during cardiac surgery. Approval by the European Medicines Agency (EMA) for its current indication is limited to patients at high risk of major blood loss undergoing isolated coronary artery bypass graft surgery (iCABG). To report current real-world data on the use and certain endpoints related to the safety of aprotinin in adult patients. The Nordic aprotinin patient registry (NAPaR) received data from 83 European centres in a noninterventional, postauthorisation safety study (PASS) performed at the request of the EMA
Safety of Perioperative Aprotinin Administration During Isolated Coronary Artery Bypass Graft Surgery: Insights From the ART (Arterial Revascularization Trial) There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART. Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about
Pulmonary vascular resistance index during coronary artery bypass surgery with aprotinin. Low pulmonary vascular resistance index (PVRI) reflects favorable redundant pulmonary circulation following coronary artery bypass grafting with cardiopulmonary bypass surgery (CPB). This randomized study investigated whether aprotinin given in different modalities impacts PVRI after coronary artery bypass grafting. A total of 40 patients undergoing coronary artery bypass grafting were randomized to four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index
Aprotinin Impacts 8-Isoprostane after Coronary Artery Bypass Grafting. The lungs participate in the modulation of the circulating inflammatory factors induced by coronary artery bypass grafting. We investigated whether aprotinin-which has been suggested to interact with inflammation-influences lung passage of key inflammatory factors after coronary artery bypass grafting. A total of 40 patients undergoing coronary artery bypass grafting were randomized into four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Pulmonary artery and radial artery blood samples were collected for the evaluation of calculated lung passage (pulmonary artery/radial artery) of the pro-inflammatory factors interleukin 6 and interleukin 8, 8-isoprostane
Aprotinin vs. tranexamic acid in isolated coronary artery bypass surgery: A large multicentre observational study. Aprotinin appears to be more efficacious than lysine analogues to reduce bleeding and transfusion of blood products in high-transfusion-risk cardiac surgical patients. However, in isolated coronary artery bypass graft (CABG) surgery, the results from head-to-head trials remain less conclusive. Our objective was to compare the efficacies and safety of aprotinin and tranexamic acid (TXA) in patients undergoing isolated on-pump CABG. A multicentre before-and-after study pooling individual data from published trials and unpublished data from three other databases. Four tertiary care teaching hospitals (Haut-Lévêque Hospital in Bordeaux, Pitié-Salpêtrière Hospital and Bichat-Claude
Aprotinin prevents proteolytic epithelial sodium channel (ENaC) activation and volume retention in nephrotic syndrome. Volume retention in nephrotic syndrome has been linked to activation of the epithelial sodium channel (ENaC) by proteolysis of its γ-subunit following urinary excretion of serine proteases such as plasmin. Here we tested whether pharmacological inhibition of urinary serine protease activity might protect from ENaC activation and volume retention in nephrotic syndrome. Urine from both nephrotic mice (induced by doxorubicin injection) and nephrotic patients exhibited high aprotinin-sensitive serine protease activity. Treatment of nephrotic mice with the serine protease inhibitor aprotinin by means of subcutaneous sustained-release pellets normalized urinary serine protease
An Aprotinin Containing Fibrin Sealant Does Not Reduce Blood Loss in Total Hip Arthroplasty. Fibrin sealants are topical agents used to reduce perioperative blood loss; however, their efficacy in total hip arthroplasty (THA) remains uncertain. The purpose of this study was to determine if a fibrin sealant containing aprotinin as an antifibrinolytic agent, TISSEEL (Baxter, Deerfield, IL), reduces
Efficacy and safety of aprotinin versus placebo during spinal surgery a systematic review and metanalysis of comparative studies PROSPERO International prospective register of systematic reviews 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. The registrant confirms
Low Dose Aprotinin in High-Risk Isolated Coronary Artery Bypass Graft Patients: A Systematic Review and Meta-Analysis PROSPERO International prospective register of systematic reviews 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. The registrant confirms
S2'-subsite variations between human and mouse enzymes (plasmin, factor XIa, kallikrein) elucidate inhibition differences by TFPI-2 domain1-wildtype, Leu17Arg-mutant and aprotinin. Essentials Current antifibrinolytics - aminocaproic acid and tranexamic acid-can cause seizures or renal injury. KD1 -K , aprotinin and tranexamic acid were tested in a modified mouse tail-amputation model. S2 arginine (improved specificity towards plasmin). KD1 -K strongly inhibited human plasmin (hPm), with no inhibition of human kallikrein (hKLK) or factor XIa (hXIa). Furthermore, KD1 -K reduced blood loss comparable to aprotinin in a mouse liver-laceration model of organ hemorrhage. However, effectiveness of these antifibrinolytic agents in a model of hemorrhage mimicking extremity trauma
Aprotinin extends mechanical integrity time of cell-seeded fibrin sutures Cell therapy has the potential to treat different pathologies, including myocardial infarctions (heart attacks), although cell engraftment remains elusive with most delivery methods. Biological sutures composed of fibrin have been shown to effectively deliver human mesenchymal stem cell (MSC) to infarcted hearts. However , human MSCs rapidly degrade fibrin making cell seeding and delivery time sensitive. To delay the degradation process, we propose using Aprotinin, a proteolytic enzyme inhibitor that has been shown to slow fibrinolysis. Human MSCs seeded on fibrin sutures and incubated with Aprotinin demonstrated similar cell viability, examined using a LIVE/DEAD stain, to controls. No differences in proliferation
99mTcâ€aprotinin – optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis Technetium-99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using (99m) Tc-pertechnetate. The labelling was achieved within 25 min
Impact of Aprotinin - A Proteolytic Enzyme on Postsurgical Symptoms in Patients Undergoing Third Molar Surgeries Dealing with postoperative pain and inflammation remains an arena for never ending research. Different agents have been the subject of many studies to prevent the occurrence of unpleasant postoperative sequel. Extraction of third molars is often associated with significant deterioration in oral health related quality of life (physical, social and psychological) in immediate postoperative period. The complaints of pain, swelling and limitation of mouth opening, which ensue as a result of acute inflammatory response, are frequent consequences of postsurgical procedures involving extraction of impacted 3(rd) molars. Aprotinin, a naturally occurring protease inhibitor was assessed
Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in children. Coagulopathy is a major issue in children undergoing high-risk pediatric cardiac surgery. Use of anti-fibrinolytics is well documented in adults, but recently there are questions raised about safety and effectiveness of their use on routine use. Tranexamic acid is a potent anti-fibrinolytic, but its role is not fully understood in children. This study aims to study the benefits tranexamic acid in controlling postoperative bleeding in pediatric cardiac surgical patients. Fifty consecutive children who underwent cardiac surgery were randomized prospectively to receive either aprotinin (Group A; n = 24) or tranexamic acid (Group B; n = 26) from September 2009 to February 2010 were studied. Primary end points