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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 -
World Journal of Gastroenterology Mar 2008To study the effect of aprotinin used in orthotopic liver transplantation (OLT) on the intraoperative requirement for blood products and on the incidence of laparotomy... (Meta-Analysis)
Meta-Analysis Review
AIM
To study the effect of aprotinin used in orthotopic liver transplantation (OLT) on the intraoperative requirement for blood products and on the incidence of laparotomy for bleeding, thrombotic events and mortality.
METHODS
A systematic review of the literature in the electronic database Medline and the Clinic Trials Registry Database was performed. Literature that did not fit our study were excluded. Patients in the reviewed studies were divided into two groups; one group used aprotinin (aprotinin group) while the other did not (control group). The data in the literature that fit our requirements were recorded. Weighted mean differences (WMD) in the requirements for blood products between the aprotinin group and the control group were tested using a fixed effect model. A Z test was performed to examine their reliability; the Fleiss method of fixed effect model was used to analyze data on postoperative events, and odds ratios (ORs) were tested and merged.
RESULTS
Seven citations were examined in our study. Among them, a requirement for blood products was reported in 4 studies including 321 patients, while postoperative events were reported in 5 studies including 477 patients. The requirement for red blood cells and fresh frozen plasma in the aprotinin group was statistically lower than that in the control group (WMD=-1.80 units, 95% CI, -3.38 to -0.22; WMD=-3.99 units, 95% CI, -6.47 to -1.50, respectively). However, no significant difference was indicated in the incidence of laparotomy for bleeding, thrombotic events and mortality between the two groups. Analysis on blood loss, anaphylactic reactions and renal function was not performed in this study due to a lack of sufficient information.
CONCLUSION
Aprotinin can reduce the intraoperative requirement for blood products in OLT, and has no significant effect on the incidence of laparotomy for bleeding, thrombotic events and mortality.
Topics: Aprotinin; Blood Loss, Surgical; Blood Transfusion; Hemostatics; Humans; Intraoperative Care; Liver Transplantation; Prognosis; Treatment Outcome
PubMed: 18322960
DOI: 10.3748/wjg.14.1425 -
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 -
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 -
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 -
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 -
British Journal of Anaesthesia Jan 2000
Topics: Aprotinin; Cardiac Surgical Procedures; Hemostatics; Humans; Kidney; Perioperative Care; Serine Proteinase Inhibitors
PubMed: 10740538
DOI: 10.1093/oxfordjournals.bja.a013377 -
Advances in Clinical and Experimental... Feb 2019Aprotinin is a nonspecific serine protease inhibitor, which can inhibit plasminogen-plasmin system and matrix metalloproteinases. Aprotinin has been investigated as an...
BACKGROUND
Aprotinin is a nonspecific serine protease inhibitor, which can inhibit plasminogen-plasmin system and matrix metalloproteinases. Aprotinin has been investigated as an antitumor agent. However, its antineoplastic effects on breast cancer (BC) have not been investigated yet.
OBJECTIVES
The objective of this study was to assess the inhibitory effects of aprotinin on human BC cell lines. We assessed the effects of aprotinin on local invasion and survival of human BC cell lines MDA-MB-231, SK-BR-3 and MCF-7 in vitro.
MATERIAL AND METHODS
CHEMICON cell invasion assay kit was used to assess local invasion, and (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay was used to determine the antiproliferative activity of aprotinin. Human dermal fibroblast (HDF-1) cell line was used as control normal cells.
RESULTS
Cancer cell lines showed more invasion characteristics compared to HDF-1. Aprotinin significantly decreased the invasiveness of MDA-MB-231 in concentrations of 1 trypsin inhibitor unit (TIU)/mL, 1.3 TIU/mL and 1.7 TIU/mL in comparison with the untreated group (analysis of variance (ANOVA) p < 0.001). Treatment of SK-BR-3 with 1.3 TIU/mL aprotinin caused no significant reduction in invasiveness (p = 0.06). Treatment with different concentrations of aprotinin significantly decreased the surviving fraction and inhibited the growth of all cell lines tested in this study (analysis of variance (ANOVA) p < 0.001). Compared to cancer cell lines, normal HDF-1 cell line showed less sensitivity to antiproliferative effects of aprotinin, both in low and high doses.
CONCLUSIONS
Aprotinin significantly inhibited the growth of human breast cancer cell lines MDA-MB-231, SK-BR-3 and MCF-7, and normal fibroblast cell line HDF-1. The growth inhibitory effect was more dominant in cancer cell lines. Inhibition of local invasion by aprotinin was significant only in the case of MDA-MB-231. Future molecular studies could shed further lights on mechanisms underlying antineoplastic effects of aprotinin and its potential therapeutic effects.
Topics: Antineoplastic Agents; Aprotinin; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasm Invasiveness; Serine Proteinase Inhibitors
PubMed: 30411549
DOI: 10.17219/acem/89770 -
Anesthesiology Jul 2015
Review
Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Clinical Trials as Topic; Humans
PubMed: 25950230
DOI: 10.1097/ALN.0000000000000688 -
PloS One 2015Neonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing...
BACKGROUND
Neonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing the requirement for a blood transfusion following a cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim of this study was to compare the efficacy and adverse effects of aprotinin and tranexamic acid in neonates undergoing open-heart surgery at a single centre.
METHODS
Between October 2003 and March 2008, perioperative data of 552 consecutive neonatal patients undergoing open-heart surgery in Children's Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275 patients received aprotinin with or without tranexamic acid (Group C). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained identical. Postoperative complications and in-hospital mortality were the primary study endpoints.
RESULTS
Body weight and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores were statistically comparable among the three groups. No statistically significant differences were observed between the duration of hospitalization, chest tube drainage, reexploration for bleeding, and kidney function impairment. In Group C, less blood was transfused within 24 hours than in GroupB. Operative mortality was similar among the three groups.
CONCLUSION
No further risk and kidney injury were observed in the use of aprotinin in neonatal cardiac surgery, aprotinin demonstrated a reduced requirement for blood transfusion compared with tranexamic acid. Our data provide reasonable evidence that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic modalities in neonatal patients undergoing cardiac surgery.
Topics: Antifibrinolytic Agents; Aprotinin; Cardiac Surgical Procedures; Female; Humans; Infant, Newborn; Kaplan-Meier Estimate; Male; Retrospective Studies; Tranexamic Acid
PubMed: 25954976
DOI: 10.1371/journal.pone.0126514