Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation. The effect of two different doses of aprotinin on hemostasis in cardiopulmonary bypass surgery: similar transfusion requirements and blood loss. The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. Aprotinin decreases blood loss and homologous transfusions in patients undergoing major orthopedic surgery. Effects of minimal dose aprotinin on blood loss and fibrinolytic system-complement activation in coronary artery bypass grafting surgery. Aprotinin and dipyridamole for the safe reduction of postoperative blood loss. [Aprotinin (Antilysin Spofa)--its effect on decreasing hemorrhage in the postoperative period in hip arthroplasty].
During liver transplantation (LT), profound activation of the fibrinolytic system can contribute significantly to perioperative bleeding. Prophylactic administration of antifibrinolytic agents has been shown to reduce blood loss and the need for allogeneic transfusion in these conditions.
                This prospective randomized trial included 51 cirrhotic patients undergoing LT. Patients were randomly assigned to receive either 280 mg of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA) followed by 40 mg per kg per hour, administered from the end of the anhepatic phase until 2 hours after reperfusion of the graft, and the effects on blood loss and red blood cell (RBC) transfusion requirements were compared. Transfusion policy was standardized in all patients. In addition, the biological effects of the two drugs, as assessed by coagulation and fibrinolytic markers obtained during surgery, were evaluated in a subgroup of patients from each treatment group and compared with an historical control group that did not receive antifibrinolytic drugs.
                There was no significant difference between the two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495-8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25] units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with both drugs compared with the control group. Coagulation appeared to be activated more with AP, however, whereas fibrinolysis was inhibited more by TA.
                Blood losses and RBC transfusion requirements were comparable regardless of the drug administered. TA may be as valuable as AP for controlling fibrinolysis in LT. Various dosages of aprotinin have proven to be effective in reducing blood loss and allogeneic transfusion requirements in cardiopulmonary bypass surgery, despite the controversy surrounding the precise hemostatic mechanisms of this drug. The aim of our prospective, randomized, double-blind study was to assess differences in blood loss and transfusion requirements and the effect of two dosages of aprotinin on hemostatic activation.
                Patients undergoing coronary artery bypass grafting received high-dose aprotinin (n=28), pump-prime-only (PPO) aprotinin (n=28), or placebo (n=28).
                The high-dose and the PPO groups had a significantly lower blood loss (985 mL [95%CI 845-1,102] and 1,255 mL, [95% CI 1,025-1,406], respectively) than the placebo group (1,416 mL, 95%CI 1,248-1,612]. Transfusion requirements were lower in the aprotinin-treated groups than in the patients receiving placebo (21 units and 15 units in the high and low-dose groups vs 59 units in placebo group). As far as concerns parameters of thrombin generation, the aprotinin groups showed a significant reduction of F1+2 prothrombin fragment but not of thrombin-antithrombin complexes. There were higher levels of natural anticoagulants, i.e. antithrombin, protein C and protein S, in the high-dose aprotinin group. As regards fibrinolysis parameters, D-dimer was lower in the aprotinin groups, and the levels of alpha2-antiplasmin and plasmin-alpha2-antiplasmin complexes were raised. In summary, both dosages of aprotinin were equally effective in reducing blood loss and transfusion requirements. There was a lower activation of coagulation and fibrinolysis in cardiopulmonary bypass patients treated with aprotinin: the levels of natural anticoagulants were less decreased in the high-dose group. No differences in thrombotic complications were observed between aprotinin groups.
                Our study shows that both dosages of aprotinin are safe and effective in reducing transfusion requirements. Considering the difference in cost of using a low-dose or high-dose schedule, the former should be recommended for patients undergoing cardiopulmonary bypass surgery. Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions.
                To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar.
                Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions.
                Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram.
                The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control.
                For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury. Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.
                In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days.
                The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22).
                Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).
                Copyright 2008 Massachusetts Medical Society. Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n = 14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass. Compared with controls, aprotinin reduced blood loss, the number of patients requiring transfusions, and the mean number of transfused red cell units (all with p < 0.05), whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls. Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls (p < 0.05). Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation, without any intergroup differences. The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis, without differences between the groups. The concentrations of D-dimer, a breakdown product of cross-linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may reflect the different modes of action of the two agents, which may make aprotinin more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass. Major orthopedic surgery can be associated with dramatic blood loss, thereby requiring high-volume homologous transfusions in patients unable to benefit from blood salvage techniques. The effect of aprotinin on blood loss and transfusion requirements during orthopedic surgery for either the resection of malignancies of the removal of infected hardware was prospectively studied.
                Twenty-three patients scheduled for orthopedic surgery of the hip, femur, or pelvis for sepsis or malignant tumors, all under general anesthesia, were randomly allocated to receive during operation, in a blinded manner, either aprotinin administered as a bolus of 1.106 kallikrein inactivation units (KIU) followed by an infusion of 5 x 10(5) KIU/h, or the equivalent volume of saline. The anesthesia and perioperative management, as well as the designated transfusion criteria, were standardized. The total blood loss of each patient was evaluated using intraoperative suction losses, sponge weights, and postoperative volumetric drainage. Homologous transfusion requirements were noted. Hemoglobin and hematocrit measures, as well as coagulation and fibrinolytic pathway explorations, were performed before and after surgery. Deep venous thrombosis prophylaxis was applied, and the incidence of this complication was assessed.
                Twelve patients received aprotinin. Aprotinin reduced the total blood loss from a median of 5,305 ml (range, 3,000-9,770 ml) to a median of 1,783 ml (range, 1,140-4,955 ml; P < 0.05). A blood loss reduction of 56% during surgery and 68% on discharge from the postanesthesia care unit was observed. Seven units (range, 4-16) of packed erythrocytes were transfused per patient in the placebo group, and 3 (range, 2-5) were transfused in the aprotinin group (P < 0.05). In the aprotinin group, platelet counts were higher, and postoperative prothrombin times and D. Dimer values were lower. The activated partial thromboplastin time values showed no significant difference between the two groups. No side effects were observed in the aprotinin group. A deep venous thrombosis developed in one patient in the placebo group.
                Aprotinin treatment during major orthopedic surgery significantly reduces both blood loss and consequent homologous blood transfusion requirements. To determine whether 500,000 KIU aprotinin is effective to reduce blood loss in coronary artery bypass grafting (CABG) and to evaluate the effects of this regimen on hematologic parameters.
                Forty-four patients scheduled for primary CABG were randomly assigned to the aprotinin (n = 24) or control group (n = 20). In aprotinin group, aprotinin was administered in two equal doses (before skin incision and added to the pump prime). Ventilation time, intensive care unit stay, mediastinal tube drainage, hospitalization, transfusion requirements, and postoperative morbidities and mortality were noted. Hematologic markers of fibrinolytic activity and complement activation were also measured pre- and postoperatively.
                Although less mediastinal drainage occurred in aprotinin group, the difference was not statistically significant. Other postoperative variables like transfusion requirements, morbidities, and mortality were also found to be similar between groups. Among hematologic parameters, only postoperative levels of alpha2-antiplasmin and plasminogen activator inhibitor-1 were significantly higher in aprotinin group.
                Although plasmin inhibitors begin to rise at this very low aprotinin dosage, it is not advisable to use this aprotinin regimen in CABG patients. Aprotinin (APR) reduces postoperative blood loss but may induce thrombosis. Dipyridamole (DIP) limits platelet aggregation and may reduce the thrombotic complications associated with APR.
                To evaluate the safety and effectiveness of combined APR and DIP, we undertook a prospective randomized trial in patients undergoing cardiac operations. Patients were stratified according to risk for bleeding (low or high), and received either DIP with placebo (DIP group; n = 59) or DIP with APR (DIP + APR group; n = 56). Blood samples were obtained for the measurement of hematologic and biochemical parameters. Blood loss and transfusion requirements were documented postoperatively.
                Postoperative blood loss and transfusion requirements were significantly lower in the DIP + APR group at 6, 12, and 24 hours after bypass (p < 0.01). No significant differences were found between groups in the incidence of perioperative mortality (DIP, 0%; DIP + APR, 3%), myocardial infarction (DIP, 0%; DIP + APR, 3%), stroke (DIP, 1%; DIP + APR, 1%), or potential thrombotic events (death, myocardial infarction, and stroke: DIP, 2%; DIP + APR, 5%). In addition, these rates did not differ from those of nonparticipating matched control patients.
                Administration of both drugs simultaneously was more effective than DIP alone in reducing postoperative blood loss. A platelet inhibitor may be required to reduce the thrombotic complications associated with APR. Further studies evaluating graft patency and perioperative ischemia are necessary to confirm the potential benefits of the combination of a platelet inhibitor and APR. Aprotinin is a non-specific inhibitor of serine proteases with hemostyptic and hemostatic properties. The effect covers suppression of fibrinolysis and support of the role of thrombocytes in coagulation. In a prospective randomized study we verified whether the application of aprotinin (Antilysin Spofa, Czech Republic) in the dosage effective in cardiosurgical patients reduces blood loss and the need for blood transfusion for orthopaedic patients.
                42 patients indicated to the primary THA were randomly selected into the study and control groups. Excluded were allergic patients and those who used aprotinin before.
                Administration of 2.10(6) KIU of aprotinin was started preoperatively and is continued in the course of the first hour of surgery. In the operated on patients we recorded prior to operation and in the first post-operative morning the level of hemoglobin in blood and hematocrit, the number of infusions and blood transfusion units administered in the course of the surgery and in the post-operative period until the first post-operative morning. We recorded blood loss in the period between the surgery and the first post-operative morning. Data acquired in the patients of the studied and control groups were compared by means of ANOVA test for repeated measuring and with the use of Mann-Whitney and chi 2-test, the level of significance p < or = 0.05. During the hospitalization we the patients were checked for symptoms of deep venous trombosis and tromboembolic or other adverse events.
                Hemoglobinemia and hematocrit in both groups significantly decreased after the operation (p < 0.0005), the differences between the studied and control groups were not significant. The number of administered blood units did not differ in the examined and control groups. The frequency of blood transfusions was postoperatively higher in the control group (59.1% as compared to 30%), however, the difference was not statistically significant (p = 0.059). Blood loss in the post-operative period was higher in the control group (p = 0.048). Patients from the control group got in total blood transfusion more frequently (p = 0.032). Differences in the total frequency of blood transfusion and in the amount of post-operative blood loss were statistically significant. In the course of hospitalisation no signs of deep phlebothrombosis or thromboembolic condition were encountered in either group of patients. Complications were not recorded.
                Our results correspond with most of the published data. Blood loss of the operated on patients who were administered prior to and at the beginning of the operation in total 2.10(6) KIU of aprotinin (Antilysin Spofa) in infusion was on average by 33% less in the post-operative period and in the whole peropetive period they required less frequently blood transfusion (40% vs 73%).
                Infusion of aprotinin (Antilysin Spofa) in the dosage of the order of 106 KIU significantly reduces post-operative blood loss and frequency of transfusion in the peroperative period in patients undergoing THA.
Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.