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Wulf Dietrich - One of the best experts on this subject based on the ideXlab platform.
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Aprotinin and anaphylaxis analysis of 12 403 exposures to Aprotinin in cardiac surgery
The Annals of Thoracic Surgery, 2007Co-Authors: Wulf Dietrich, Anna Ebell, Raimund Busley, Annalaure BoulesteixAbstract:Background Hypersensitivity reactions to the nonspecific proteinase inhibitor Aprotinin may occur. The present study evaluates the incidence of hypersensitivity reactions to Aprotinin. Methods Data were prospectively collected as part of the institution's quality assurance program. The database was screened for anaphylactic reactions, especially those against Aprotinin. The definition of an allergic reaction was predefined. A severe reaction was definded as hemodynamic instability of more than 10 minutes despite high dosages of vasopressors and inotropic medication. Results Of 13,315 cardiac operations, 12,403 were done with Aprotinin, with 801 reexposures in 697 patients. Eleven reactions to Aprotinin (11 of 11,602; 0.09%, 95% confidence interval: 0.05% to 0.16%) were recorded after primary exposure, of which none was severe, while 12 reactions (12 of 801; 1.5%; 95% confidence interval: 0.86% to 2.6%) occurred after reexposure, of which 5 were severe. All severe reactions were in patients reexposed to Aprotinin within 6 months after previous exposure. There was no reaction observed in patients reexposed to Aprotinin within 3 days after the last exposure (n = 42). The incidence of hypersensitivity reactions was 4.1%, 1.9%, and 0.4% in the less than 6 months, 6 to 12 months, and more than 12 months reexposure intervals, respectively. Conclusions The risk of hypersensitivity reactions is low after primary exposure to Aprotinin. This risk after reexposure reaches a maximum between the fourth day and the 30th day after previous exposure and declines considerably after 6 months. Consequently, application of Aprotinin carries a high risk between the fourth and the 30th day after previous exposure, and cannot be recommended for the first 6 months, but is justifiable in previously Aprotinin-exposed patients with a high risk of bleeding after this interval.
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high dose Aprotinin in cardiac surgery is high dose high enough an analysis of 8281 cardiac surgical patients treated with Aprotinin
Anesthesia & Analgesia, 2006Co-Authors: Wulf Dietrich, Raimund Busley, Monika KrinerAbstract:In this retrospective analysis we tested the hypothesis that Aprotinin doses of more than 6 x 10(6) kallikrein inhibiting units (KIU) per patient may be more effective in reducing bleeding compared with the high-dose regimen of 5-6 x 10(6) KIU Aprotinin. The Aprotinin doses administered for 8281 adult cardiac surgical patients were correlated to body weight and time of operation and calculated in KIU per kg body weight and minute of operation. Linear and logistic regression models were designed to detect potential associations between dose and postoperative bleeding, transfusion, and other covariates. The 6-h chest tube drainage in the lowest quartile dosing group was 447 +/- 319 mL (mean +/- sd) compared with 360 +/- 290 mL in the highest quartile dosing group (P or=2 mg/dL postoperatively, 6.4% in the highest dosing group vs 10.0% in the lowest dosing group; P < 0.01) was lower with higher doses of Aprotinin. Thus, there was no association between Aprotinin dose and renal function. Our results support the hypothesis that a more individualized Aprotinin regimen with potentially higher doses may optimize the effectiveness of Aprotinin therapy in cardiac surgery.
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high dose Aprotinin reduces activation of hemostasis allogeneic blood requirement and duration of postoperative ventilation in pediatric cardiac surgery
The Annals of Thoracic Surgery, 2003Co-Authors: H Mossinger, Wulf Dietrich, Marianne Jochum, Siegmund Braun, Hans Meisner, J A RichterAbstract:Abstract Background Though multiple studies have affirmed the effectiveness of Aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. Methods In a double-blind, randomized, and placebo-controlled study, the efficacy of Aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of Aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 × 10 4 KIU/kg plus a bolus of 5 × 10 5 KIU (not weight adjusted) added to the pump prime. Results Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 ± 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 ± 2.9 nmol/L vs 14.5 ± 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 ± 0.6 ng/mL vs 2.3 ± 3.1 ng/mL; p p p 2 /FIO 2 172 [IQR 128] mm Hg vs 127 [74]; p p Conclusions High-dose Aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the Aprotinin group.
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anaphylactic reactions to Aprotinin reexposure in cardiac surgery relation to antiAprotinin immunoglobulin g and e antibodies
Anesthesiology, 2001Co-Authors: Wulf Dietrich, Paul Spath, Michael Zuhlsdorf, H Dalichau, P G Kirchhoff, Hermann Kuppe, Dieter U Preiss, Gabriele MayerAbstract:Background: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As Aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to Aprotinin and the relation to preformed antiAprotinin immunoglobulin (Ig)G and IgE antibodies. Methods: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to Aprotinin between 1995 and 1996. AntiAprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of Aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. Results: In 121 cases (71 adults, 46 children), a mean Aprotinin reexposure interval of 1,654 days (range, 16 ‐7,136 days) was observed. Preoperative antiAprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score 10; IgE, RAST score > 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51‐7.1%) experienced an anaphylactic reaction after Aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0 ‐3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. Conclusions: Quantitative detection of antiAprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiAprotinin IgG may identify patients at risk for developing an anaphylactic reaction to Aprotinin reexposure. Aprotinin (Trasylol, Bayer Vital, Leverkusen, Germany) reduces perioperative bleeding during cardiac surgery. 1,2 A polypeptide (58 amino acids; 6.5 kd) 3 serine proteinase inhibitor, Aprotinin is thought to reduce bleeding through inhibiting the contact phase activation of hemostasis, preventing fibrinolysis, 4 and reducing thrombin generation. 5
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prevalence of anaphylactic reactions to Aprotinin analysis of two hundred forty eight reexposures to Aprotinin in heart operations
The Journal of Thoracic and Cardiovascular Surgery, 1997Co-Authors: Wulf Dietrich, P Spath, A Ebell, J A RichterAbstract:The efficacy of Aprotinin to reduce intraoperative bleeding tendency in cardiac operations has been demonstrated in several studies. Aprotinin is a polybasic polypeptide and has antigenic properties. Anaphylactic reactions to Aprotinin have been described. The aim of the present study was to evaluate the prevalence of adverse reactions to reexposure to high-dose Aprotinin. The clinical outcome of all patients undergoing heart operations in our institution between 1988 and 1995 with at least two exposures to Aprotinin was investigated. There were 248 reexposures to Aprotinin in 240 patients: 101 adult and 147 pediatric cases. The total Aprotinin doses were 4.9 × 106 (interquartile range 2 × 106) KIU (adults) and 1.3 × 106 (interquartile range 1.2 × 106) KIU (pediatric patients). The time between the first and second Aprotinin exposures was 344 (interquartile range 1039) days. Seven adverse reactions to Aprotinin were found (2.8%). The severity of the reaction ranged from mild (no intervention) to severe (longer-lasting circulatory depression despite vasopressor therapy). All patients survived the event. Patients with an interval less than 6 months since the previous exposure had a statistically higher incidence of adverse reactions than patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two patients reacted to a test dose of 10,000 KIU Aprotinin. Pretreatment with antihistaminics was done in 60% of the patients. We recommend the following procedure for reexposure with high-dose Aprotinin: (1) delay of the first bolus injection of Aprotinin until the surgeon is ready to begin cardiopulmonary bypass, (2) test dose of 10,000 KIU Aprotinin in all patients with Aprotinin treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance of reexposure within the first 6 months after the previous exposure to Aprotinin. With these precautions a reexposure to Aprotinin in patients with a high risk of bleeding is justified, because the benefits of Aprotinin treatment outweigh the relative risk of a serious allergic reaction. (J Thorac Cardiovasc Surg 1997;113:194-201)
Francis G Spinale - One of the best experts on this subject based on the ideXlab platform.
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early postoperative outcomes and blood product utilization in adult cardiac surgery the post Aprotinin era
Circulation, 2011Co-Authors: Stacia M Desantis, Walter E Uber, Matthew J Toole, John M Kratz, Margaret J Wheat, Martha R Stroud, John S Ikonomidis, Francis G SpinaleAbstract:Background— Aprotinin was a commonly used pharmacological agent for homeostasis in cardiac surgery but was discontinued, resulting in the extensive use of lysine analogues. This study tested the hypothesis that early postoperative adverse events and blood product utilization would affected in this post-Aprotinin era. Methods and Results— Adult patients (n=781) undergoing coronary artery bypass, valve replacement, or both from November 1, 2005, to October 31, 2008, at a single institution were included. Multiple logistic regression modeling and propensity scoring were performed on 29 preoperative and intraoperative variables in patients receiving Aprotinin (n=325) or lysine analogues (n=456). The propensity-adjusted relative risk (RR) for the intraoperative use of packed red blood cells (RR, 0.75; 95% confidence interval [CI], 0.57 to 0.99), fresh frozen plasma (RR, 0.37; 95% CI, 0.21 to 0.64), and cryoprecipitate (RR:0.06; 95% CI, 0.02 to 0.22) were lower in the Aprotinin versus lysine analog group (all P <0.05). The risk for mortality (RR, 0.53; 95% CI, 0.16 to 1.79) and neurological events (RR, 0.87; 95% CI, 0.35 to 2.18) remained similar between groups, whereas a trend for reduced risk for renal dysfunction was observed in the Aprotinin group. Conclusions— In the post-Aprotinin era, with the exclusive use of lysine analogues, the relative risk of early postoperative outcomes such as mortality and renal dysfunction have not improved, but the risk for the intraoperative use of blood products has increased. Thus, improvements in early postoperative outcomes have not been realized with the discontinued use of Aprotinin, but rather increased blood product use has occurred with the attendant costs and risks inherent with this strategy.
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abstract 12431 continuous localized monitoring of plasmin activity identifies differential and regional effects of the serine protease inhibitor Aprotinin relevance to antifibrinolytic therapy
Circulation, 2010Co-Authors: Daryl L Reust, Jennifer A Dixon, Richard A Mckinney, Risha K Patel, William T Rivers, Rupak Mukherjee, Robert E Stroud, Scott Reeves, James H Abernathy, Francis G SpinaleAbstract:Background: Antifibrinolytic therapy, such as the use of the serine protease inhibitor Aprotinin, was a mainstay for hemostasis following cardiac surgery. However, Aprotinin was empirically dosed, ...
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Aprotinin in cardiac surgery a review of conventional and novel mechanisms of action
Anesthesia & Analgesia, 2007Co-Authors: Matthew D Mcevoy, Scott Reeves, J G Reves, Francis G SpinaleAbstract:Induction of the coagulation and inflammatory cascades can cause multiorgan dysfunction after cardiopulmonary bypass (CPB). In light of these observations, strategies that can stabilize the coagulation process as well as attenuate the inflammatory response during and after cardiac surgery are important. Aprotinin has effects on hemostasis. In addition, Aprotinin may exert multiple biologically relevant effects in the context of cardiac surgery and CPB. For example, it decreases neutrophil and macrophage activation and chemotaxis, attenuates release and activation of proinflammatory cytokines, and reduces oxidative stress. Despite these perceived benefits, the routine use of Aprotinin in cardiac surgery with CPB has been called into question. In this review, we examined this controversial drug by discussing the classical and novel pathways in which Aprotinin may be operative in the context of cardiac surgery.
Jeffrey A Hubbell - One of the best experts on this subject based on the ideXlab platform.
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human kunitz type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials
Biomaterials, 2017Co-Authors: Priscilla S Briquez, Peter Frey, Kristen M Lorentz, Hans M Larsson, Jeffrey A HubbellAbstract:Abstract Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of Aprotinin. Here, we aimed to develop a human-derived substitute to Aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than Aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as Aprotinin's is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro , outperforming Aprotinin. In vivo , our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which Aprotinin did not show efficacy, thus qualifying it as a competitive substitute of Aprotinin in fibrin sealants.
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engineered Aprotinin for improved stability of fibrin biomaterials
Biomaterials, 2011Co-Authors: Kristen Marie Lorentz, Stephan Kontos, Peter Frey, Jeffrey A HubbellAbstract:Fibrin has been long used clinically for hemostasis and sealing, yet extension of use in other applications has been limited due to its relatively rapid resorption in vivo, even with addition of Aprotinin or other protease inhibitors. We report an engineered Aprotinin variant that can be immobilized within fibrin and thus provide extended longevity. When recombinantly fused to a transglutaminase substrate domain from α(2)-plasmin inhibitor (α(2)PI(1-8)), the resulting variant, Aprotinin-α(2)PI(1-8), was covalently crosslinked into fibrin matrices during normal thrombin/factor XIIIa-mediated polymerization. Challenge with physiological plasmin concentrations revealed that Aprotinin-α(2)PI(1-8)-containing matrices retained 78% of their mass after 3 wk, whereas matrices containing wild type (WT) Aprotinin degraded completely within 1 wk. Plasmin challenge of commercial sealants Omrixil and Tisseel, supplemented with Aprotinin-α(2)PI(1-8) or WT Aprotinin, showed extended longevity as well. When seeded with human dermal fibroblasts, Aprotinin-α(2)PI(1-8)-supplemented matrices supported cell growth for at least 33% longer than those containing WT Aprotinin. Subcutaneously implanted matrices containing Aprotinin-α(2)PI(1-8) were detectable in mice for more than twice as long as those containing WT Aprotinin. We conclude that our engineered recombinant Aprotinin variant can confer extended longevity to fibrin matrices more effectively than WT Aprotinin in vitro and in vivo.
J A Richter - One of the best experts on this subject based on the ideXlab platform.
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high dose Aprotinin reduces activation of hemostasis allogeneic blood requirement and duration of postoperative ventilation in pediatric cardiac surgery
The Annals of Thoracic Surgery, 2003Co-Authors: H Mossinger, Wulf Dietrich, Marianne Jochum, Siegmund Braun, Hans Meisner, J A RichterAbstract:Abstract Background Though multiple studies have affirmed the effectiveness of Aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. Methods In a double-blind, randomized, and placebo-controlled study, the efficacy of Aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of Aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 × 10 4 KIU/kg plus a bolus of 5 × 10 5 KIU (not weight adjusted) added to the pump prime. Results Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 ± 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 ± 2.9 nmol/L vs 14.5 ± 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 ± 0.6 ng/mL vs 2.3 ± 3.1 ng/mL; p p p 2 /FIO 2 172 [IQR 128] mm Hg vs 127 [74]; p p Conclusions High-dose Aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the Aprotinin group.
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prevalence of anaphylactic reactions to Aprotinin analysis of two hundred forty eight reexposures to Aprotinin in heart operations
The Journal of Thoracic and Cardiovascular Surgery, 1997Co-Authors: Wulf Dietrich, P Spath, A Ebell, J A RichterAbstract:The efficacy of Aprotinin to reduce intraoperative bleeding tendency in cardiac operations has been demonstrated in several studies. Aprotinin is a polybasic polypeptide and has antigenic properties. Anaphylactic reactions to Aprotinin have been described. The aim of the present study was to evaluate the prevalence of adverse reactions to reexposure to high-dose Aprotinin. The clinical outcome of all patients undergoing heart operations in our institution between 1988 and 1995 with at least two exposures to Aprotinin was investigated. There were 248 reexposures to Aprotinin in 240 patients: 101 adult and 147 pediatric cases. The total Aprotinin doses were 4.9 × 106 (interquartile range 2 × 106) KIU (adults) and 1.3 × 106 (interquartile range 1.2 × 106) KIU (pediatric patients). The time between the first and second Aprotinin exposures was 344 (interquartile range 1039) days. Seven adverse reactions to Aprotinin were found (2.8%). The severity of the reaction ranged from mild (no intervention) to severe (longer-lasting circulatory depression despite vasopressor therapy). All patients survived the event. Patients with an interval less than 6 months since the previous exposure had a statistically higher incidence of adverse reactions than patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two patients reacted to a test dose of 10,000 KIU Aprotinin. Pretreatment with antihistaminics was done in 60% of the patients. We recommend the following procedure for reexposure with high-dose Aprotinin: (1) delay of the first bolus injection of Aprotinin until the surgeon is ready to begin cardiopulmonary bypass, (2) test dose of 10,000 KIU Aprotinin in all patients with Aprotinin treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance of reexposure within the first 6 months after the previous exposure to Aprotinin. With these precautions a reexposure to Aprotinin in patients with a high risk of bleeding is justified, because the benefits of Aprotinin treatment outweigh the relative risk of a serious allergic reaction. (J Thorac Cardiovasc Surg 1997;113:194-201)
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influence of high dose Aprotinin on anticoagulation heparin requirement and celite and kaolin activated clotting time in heparin pretreated patients undergoing open heart surgery a double blind placebo controlled study
Anesthesiology, 1995Co-Authors: Wulf Dietrich, Michael Spannagl, Marianne Jochum, Siegmund Braun, Gerd Dilthey, J A RichterAbstract:BACKGROUND: Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of Aprotinin. The current study was designed to test the efficacy of Aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of Aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity. METHODS: In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose Aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), Aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded. RESULTS: Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05). CONCLUSIONS: Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of Aprotinin, because the prolonged CACT in the Aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of Aprotinin.
Scott Reeves - One of the best experts on this subject based on the ideXlab platform.
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differential effects of Aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery
The Journal of Thoracic and Cardiovascular Surgery, 2012Co-Authors: Eric M Graham, Andrew M Atz, Jenna Gillis, Stacia M Desantis, Lauren A Haney, Rachael L Deardorff, Walter E Uber, Scott Reeves, Francis X Mcgowan, Scott M BradleyAbstract:Objective Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that Aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. Methods This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either Aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. Results Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving Aprotinin compared with tranexamic acid ( P P P = .02), and inotropic requirements at 24 and 36 hours ( P P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the Aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. Conclusions Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that Aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes.
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abstract 12431 continuous localized monitoring of plasmin activity identifies differential and regional effects of the serine protease inhibitor Aprotinin relevance to antifibrinolytic therapy
Circulation, 2010Co-Authors: Daryl L Reust, Jennifer A Dixon, Richard A Mckinney, Risha K Patel, William T Rivers, Rupak Mukherjee, Robert E Stroud, Scott Reeves, James H Abernathy, Francis G SpinaleAbstract:Background: Antifibrinolytic therapy, such as the use of the serine protease inhibitor Aprotinin, was a mainstay for hemostasis following cardiac surgery. However, Aprotinin was empirically dosed, ...
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Aprotinin in cardiac surgery a review of conventional and novel mechanisms of action
Anesthesia & Analgesia, 2007Co-Authors: Matthew D Mcevoy, Scott Reeves, J G Reves, Francis G SpinaleAbstract:Induction of the coagulation and inflammatory cascades can cause multiorgan dysfunction after cardiopulmonary bypass (CPB). In light of these observations, strategies that can stabilize the coagulation process as well as attenuate the inflammatory response during and after cardiac surgery are important. Aprotinin has effects on hemostasis. In addition, Aprotinin may exert multiple biologically relevant effects in the context of cardiac surgery and CPB. For example, it decreases neutrophil and macrophage activation and chemotaxis, attenuates release and activation of proinflammatory cytokines, and reduces oxidative stress. Despite these perceived benefits, the routine use of Aprotinin in cardiac surgery with CPB has been called into question. In this review, we examined this controversial drug by discussing the classical and novel pathways in which Aprotinin may be operative in the context of cardiac surgery.