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International Journal of Molecular... Jul 2023Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical "magic shotgun". Until 2007, APR was widely used as an antithrombotic and... (Review)
Review
Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical "magic shotgun". Until 2007, APR was widely used as an antithrombotic and anti-inflammatory drug in cardiac and noncardiac surgeries for reduction of bleeding and thus limiting the need for blood transfusion. The ability of APR to inhibit proteolytic activation of some viruses leads to its use as an antiviral drug for the prevention and treatment of acute respiratory virus infections. However, due to incompetent interpretation of several clinical trials followed by incredible controversy in the literature, the usage of APR was nearly stopped for a decade worldwide. In 2015-2020, after re-analysis of these clinical trials' data the restrictions in APR usage were lifted worldwide. This review discusses antiviral mechanisms of APR action and summarizes current knowledge and prospective regarding the use of APR treatment for diseases caused by RNA-containing viruses, including influenza and SARS-CoV-2 viruses, or as a part of combination antiviral treatment.
Topics: Humans; Aprotinin; SARS-CoV-2; Prospective Studies; COVID-19; Antiviral Agents; Respiration Disorders
PubMed: 37446350
DOI: 10.3390/ijms241311173 -
European Spine Journal : Official... Oct 2004Aprotinin is a potent pharmacological agent that reduces bleeding and limits blood transfusion requirements in current surgical practice. Many studies have been... (Review)
Review
Aprotinin is a potent pharmacological agent that reduces bleeding and limits blood transfusion requirements in current surgical practice. Many studies have been conducted in orthopedic surgery. In several trials performed in total hip replacement (THR) and total knee replacement (TKN) patients, aprotinin only moderately decreased blood-loss-replacement requirements. Conversely, when aprotinin was used in patients at high risk for bleeding (cancer, sepsis, redone surgery), it developed a potent hemostatic activity and decreased blood transfusion significantly. No increase in deep vein thrombosis and pulmonary embolism was observed. The only major side effect could be the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk major orthopedic operations. The decision to use aprotinin should be guided by a risk/benefit analysis.
Topics: Aprotinin; Blood Loss, Surgical; Double-Blind Method; Hemostatics; Humans; Orthopedic Procedures; Randomized Controlled Trials as Topic; Risk Assessment; Spinal Fusion; Thrombosis; Treatment Outcome
PubMed: 15235943
DOI: 10.1007/s00586-004-0744-y -
Anaesthesia Jan 2015There is a considerable difference between the mechanism of action of the lysine analogues, tranexamic acid and epsilon-aminocaproic acid, and the serine protease... (Review)
Review
There is a considerable difference between the mechanism of action of the lysine analogues, tranexamic acid and epsilon-aminocaproic acid, and the serine protease inhibitor aprotinin. Aprotinin acts to inactivate free plasmin, but with little effect on bound plasmin, whereas the lysine analogues are designed to prevent excessive plasmin formation by fitting into plasminogen's lysine-binding site to prevent the binding of plasminogen to fibrin. Aprotinin is associated with a reduction in bleeding and transfusion requirements following major surgery, and has a dose-response profile, compared with no dose-response effect in the one study investigating tranexamic acid in cardiac surgical patients. Following its withdrawal in 2007, which is explained in detail in this review, the regulators have now licensed aprotinin for myocardial revascularisation only, which is relatively low-risk for bleeding.
Topics: Animals; Aprotinin; Hemorrhage; Hemostatics; Humans; Tranexamic Acid
PubMed: 25440394
DOI: 10.1111/anae.12907 -
The Journal of Thoracic and... Mar 2008
Topics: Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Hemostatics; Humans; Postoperative Hemorrhage; Prognosis; Risk Assessment; Survival Analysis; Treatment Outcome
PubMed: 18329458
DOI: 10.1016/j.jtcvs.2007.12.025 -
BMJ (Clinical Research Ed.) Sep 1991
Topics: Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Hemorrhage; Humans; Postoperative Complications
PubMed: 1717088
DOI: 10.1136/bmj.303.6804.660 -
British Journal of Anaesthesia May 2013
Review
Topics: Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Drug and Narcotic Control; Evidence-Based Medicine; Hemostasis, Surgical; Hemostatics; Humans; Practice Guidelines as Topic
PubMed: 23599511
DOI: 10.1093/bja/aet008 -
European Journal of Cardio-thoracic... Nov 2009
Topics: Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Hemostasis, Surgical; Hemostatics; Humans
PubMed: 19595607
DOI: 10.1016/j.ejcts.2009.05.015 -
British Journal of Anaesthesia Dec 1994
Topics: Aprotinin; Blood Coagulation; Blood Platelets; Endothelium, Vascular; Hemostasis; Humans; Randomized Controlled Trials as Topic; Thrombosis
PubMed: 7533511
DOI: 10.1093/bja/73.6.734 -
The New England Journal of Medicine Nov 2006
Topics: Antifibrinolytic Agents; Aprotinin; Cardiac Surgical Procedures; Data Interpretation, Statistical; Drug Approval; Humans; Research Design; United States; United States Food and Drug Administration
PubMed: 17124026
DOI: 10.1056/NEJMe068271 -
Intensive Care Medicine Jan 2014
Topics: Aprotinin; Cardiac Surgical Procedures; Female; Hemostatics; Hospital Mortality; Humans; Male
PubMed: 24154674
DOI: 10.1007/s00134-013-3130-6