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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 -
The Journal of Thoracic and... Jan 2013
Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Humans; Postoperative Hemorrhage
PubMed: 23062411
DOI: 10.1016/j.jtcvs.2012.09.026 -
BMJ (Clinical Research Ed.) Nov 1991
Topics: Aprotinin; Cardiac Surgical Procedures; Humans; Partial Thromboplastin Time; Whole Blood Coagulation Time
PubMed: 1722126
DOI: 10.1136/bmj.303.6814.1401-a -
Proceedings of the Royal Society of... Sep 1965
Topics: Adult; Aprotinin; Diagnosis, Differential; Humans; Male; Malignant Carcinoid Syndrome
PubMed: 5294163
DOI: 10.1177/003591576505800920 -
The Annals of Thoracic Surgery Apr 1998Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia.... (Review)
Review
Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia. Clinical and novel experimental strategies to reduce bleeding and the need for blood and blood-product transfusions are the focus of this review. Preoperative assessment of the patient will identify drug-induced, acquired, or inherited coagulation defects that may contribute to this problem. The main attention is directed to the perioperative period, and broad areas discussed include the preoperative use of erythropoietin to increase red blood cell mass, autologous donation either preoperatively or before bypass, autotransfusion/hemofiltration, and acceptance of relative anemia both during the operation and into the postoperative period. A further, often overlooked, management strategy in treating major coagulopathies is the consideration of the cost and half-lives of the coagulation factors in individual blood components. Prevention of bleeding has become possible both by manipulation of the control of coagulation and inflammatory processes and by the introduction of pharmacologic agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the management of excess bleeding. It is a serine protease inhibitor and has several possible mechanisms of action, including inhibition of the plasma enzyme systems activated by contact with the foreign surface of the bypass circuit and preservation of platelet function. Safety issues include the possibility of hypersensitivity and anaphylactic reaction on a second exposure. Concerns that aprotinin may induce a prothrombotic or coagulant state have no basis in theory or any good evidence in the current literature. A recent study specifically sought to identify the presence of disseminated microvascular platelet-fibrin thrombi present at autopsy in patients who had received aprotinin therapy. The study concluded that diffuse platelet-fibrin thrombi were not a direct complication of aprotinin therapy. Finally, modern molecular biology has led to the recent development of an inhibitor for factor IXa that competitively replaced IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa. This compound is under investigation in animal studies. These have so far shown efficacy in reducing blood loss after bypass in comparison with standard heparin anticoagulation.
Topics: Aprotinin; Blood Transfusion; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Hemorrhage; Hemostasis, Surgical; Hemostatics; Humans; Intraoperative Complications; Reoperation; Risk Factors
PubMed: 9563396
DOI: 10.1016/s0003-4975(98)00070-8 -
The Journal of Thoracic and... Dec 1995Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety... (Comparative Study)
Comparative Study
Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.
Topics: Aortic Dissection; Anticoagulants; Aortic Aneurysm; Aprotinin; Blood Transfusion; Case-Control Studies; Female; Heart Arrest, Induced; Hemostatics; Hospital Mortality; Humans; Hypothermia, Induced; Incidence; Male; Middle Aged; Postoperative Care; Postoperative Complications; Retrospective Studies
PubMed: 8523871
DOI: 10.1016/S0022-5223(95)70021-8 -
European Spine Journal : Official... Jun 2012A retrospective review of consecutive adult patients undergoing scoliosis correction surgery was performed to compare the effects of aprotinin and tranexamic acid in... (Comparative Study)
Comparative Study
PURPOSE
A retrospective review of consecutive adult patients undergoing scoliosis correction surgery was performed to compare the effects of aprotinin and tranexamic acid in blood conservation and to define a comprehensive blood conservation strategy for such surgery.
METHODS
Medical records of all patients who underwent scoliosis correction surgery in this unit between January 2003 and December 2008 were reviewed. The patients were divided into three cohorts: group 1 receiving no antifibrinolytics, group 2 aprotinin and group 3 tranexamic acid. Information was collected regarding number of vertebral levels fused, pre- and post-operative haemoglobin, intra-operative blood loss and peri-operative autologous and allogenic blood transfusion performed.
RESULTS
Aprotinin was used in 28 patients (38%), tranexamic acid in 26 (36%), while 19 (26%) received no antifibrinolytics. 21 patients had anterior surgery, 34 patients had posterior surgery and 18 had combined anterior and posterior procedures. Mean blood loss in the patients who received aprotinin and tranexamic acid was 710 and 738 ml, respectively. This was significantly less than the patients receiving no antifibrinolytics (972 ml, p = 0.037). Blood transfusion was required in only two patients undergoing anterior correction surgery.
CONCLUSION
Aprotinin and tranexamic acid reduce blood loss in adult spinal deformity correction surgery. With aprotinin being unavailable for clinical use, we recommend the use of tranexamic acid along with other blood conservation measures for adult spinal deformity correction surgery.
Topics: Adolescent; Adult; Aged; Aprotinin; Blood Loss, Surgical; Female; Hemostasis, Surgical; Hemostatics; Humans; Male; Middle Aged; Retrospective Studies; Scoliosis; Spinal Fusion; Tranexamic Acid; Young Adult
PubMed: 22402839
DOI: 10.1007/s00586-012-2205-3 -
Annals of Cardiac Anaesthesia 2020Cardiac surgery is usually associated with significant blood loss, which often necessitates blood transfusion. In order to decrease the risks associated with the latter,... (Review)
Review
Cardiac surgery is usually associated with significant blood loss, which often necessitates blood transfusion. In order to decrease the risks associated with the latter, pharmacological as well as nonpharmacological strategies have been used to reduce blood loss. Among the pharmacological approaches, antifibrinolytic drugs are the mainstay. Aprotinin, which was the first ubiquitously used drug, fell into disrepute only to re-emerge after much debate. The decline of aprotinin paved the way for the lysine analogs. However, we must be aware with the side effects of these drugs as well as the dose modification required in special situations. Nonsaccharide glycosaminoglycans have been under investigation to overcome the drawbacks of the lysine analogs. It remains to be seen whether these drugs can replace the traditional antifibrinolytics.
Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Glycosaminoglycans; Hemostatics; Humans
PubMed: 32275035
DOI: 10.4103/aca.ACA_205_18 -
Medicinal Research Reviews Nov 2014Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical... (Review)
Review
Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical in preventing adverse consequences arising from plasmin overactivity, e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and ε-aminocaproic acid, two small molecule plasmin inhibitors, are currently used in the clinic. Several molecules have been designed utilizing covalent, but reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type. Allosteric inhibitors of plasmin have also been designed including small molecule lysine analogs that bind to plasmin's kringle domain(s) and sulfated glycosaminoglycan mimetics that bind to plasmin's catalytic domain. Plasmin inhibitors have also been explored for resolving other disease states including cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This review highlights functional and structural aspects of plasmin inhibitors with the goal of advancing their design.
Topics: Antifibrinolytic Agents; Aprotinin; Benzamidines; Dipeptides; Drug Design; Fibrinolysin; Fibrinolysis; Guanidines; Humans; Phenylalanine; Serine Proteinase Inhibitors
PubMed: 24659483
DOI: 10.1002/med.21315 -
Liver Transplantation : Official... Jan 2005This article reviews the current status and controversies of the 3 commonly used antifibrinolytics-epsilon-aminocaproic acid, tranexamic acid and aprotinin-during liver... (Review)
Review
This article reviews the current status and controversies of the 3 commonly used antifibrinolytics-epsilon-aminocaproic acid, tranexamic acid and aprotinin-during liver transplantation. There is no general consensus on how, when or which antifibrinolytics should be used in liver transplantation. Although these drugs appear to reduce blood loss and decrease transfusion requirements during liver transplantation, their use is not supported uniformly in clinical trials. Aprotinin has been studied more extensively in clinical trials and appear to offer more advantages compared to two other antifibrinolytics. Because of the diverse population of liver transplant recipients and the potential adverse effects of antifibrinolytics, especially life-threatening thromboembolism, careful patient selection and close monitoring is prudent. Further studies addressing the risks and benefits of antifibrinolytics in the setting of liver transplantation are warranted.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Humans; Liver Transplantation; Thromboembolism; Tranexamic Acid
PubMed: 15690531
DOI: 10.1002/lt.20275