Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization

One hundred sixty-five patients undergoing primary myocardial revascularization were prospectivelyentered into a randomized, double-blind, placebo-controlled study, in a single institution, in order to determine the influence of high- and low-dose aprotinin application on early coronary artery bypass graft patency. All patients were operated on by the same team and the three treatment groups were comparable in all demographic data and surgical variables. Postoperative chest tube drainage and transfusion requirements were significantly reduced in patients receiving high or low doses of aprotinin. In all patients vein and internal mammary artery graft patency was assessed by control coronary angiograms 4 to 15 days (median 8.2 days) postoperatively. In the high-dose aprotinin group, 140 of 142 vein grafts and in the low-dose aprotinin group all of the 128 vein grafts were patent compared with 138 of 139 in the placebo group. The difference was not statistically significant (P> 0.05). All pedicled internal mammary artery grafts were patent in the three treatment groups. The prevalence of perioperative myocardial infarction was evaluated by serial creatine kinase-myocardial band (CK-MB) isoenzyme measurements and by electrocardiographic recordings. No additional changes that could be attributed to aprotinin were observed. In conclusion, these results suggest that perioperative myocardial infraction secondary to aprotinin-induced native coronary artery or conduit thrombosis is not increased by aprotinin in patients undergoing primary myocardial revascularization.     

Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Although low-dose aprotinin administered after cardiopulmonary bypass has been reported to reduce mediastinal blood loss and blood product requirements in patients not taking aspirin, it is unknown whether low-dose postoperative aprotinin has any beneficial effects in patients undergoing coronary artery bypass operations who are at high risk of excessive postoperative bleeding and increased transfusion requirements because of aspirin use until just before the operation. METHODS: Fifty-five patients undergoing primary coronary artery operations with cardiopulmonary bypass who continued taking aspirin (150 mg/d) until the day before the operation were enrolled in a prospective, randomized, double-blind trial to receive a single dose of either placebo (n = 29) or 2 x 10(6) kallikrein inhibiting units of aprotinin (n = 26) at the time of sternal skin closure. RESULTS: Patients in the aprotinin group had a lower rate (28 +/- 18 vs 43 +/- 21 mL/h [mean +/- standard deviation], P <.005) and total volume of mediastinal drainage (955 +/- 615 vs 1570 +/- 955 mL, P <.007), as well as a shorter duration of mediastinal drain tube insertion (24.4 +/- 13.8 vs 31.3 +/- 16.5 hours, P <.05). In addition, a smaller proportion of patients receiving aprotinin required a blood product (31% vs 62%, P =.03), resulting in a reduction in the use of packed cells by 47% (P =.05), platelets by 77% (P =.01), fresh frozen plasma by 88% (P =.03), and total blood products by 68% (P =.01) in this group. CONCLUSIONS: These results suggest that postoperative administration of low-dose aprotinin in patients taking aspirin until just before primary coronary artery operations with cardiopulmonary bypass not only reduces the rate and total amount of postoperative mediastinal blood loss but also lowers postoperative blood product use.     

Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass.

BACKGROUND: Aprotinin therapy is now widely used during cardiac surgery. This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo. METHODS: In a double blind, randomized study, three groups of 50 patients received high-dose aprotinin costing AUS$614 per patient (AUS$ = Australian dollars), low-dose aprotinin costing AUS$220 per patient or placebo. Resource use influenced by aprotinin therapy was measured. RESULTS: Both doses were effective in reducing chest drainage and postoperative transfusion requirements, high-dose being more effective than low-dose. Both doses reduced the rate of reoperations for hemostasis. A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient, respectively. If the demonstrated less significant reductions in operating room and ward stay are included, these savings become AUS$463 and AUS$715, respectively. Alternately, if cross-matches are replaced by group-and-hold and cell savers are not used, the savings per patient would be AUS$196 and AUS$467, respectively. CONCLUSIONS: While high-dose aprotinin is clinically more effective than low-dose aprotinin, low-dose therapy demonstrates greater cost savings.     

Aprotinin decreases exposure to allogeneic blood during primary unilateral total hip replacement

BACKGROUND: Aprotinin, a hemostatic agent, regulates fibrinolysis, modulates the intrinsic coagulation pathway, stabilizes platelet function, and exhibits anti-inflammatory properties through inhibition of serine proteases, such as trypsin, plasmin, and kallikrein. Aprotinin has been used successfully for many years in cardiac operations, and there have been preliminary investigations of its use in hip replacement operations. The objectives of this multicenter, randomized, placebo-controlled, double-blind trial were to evaluate the efficacy and safety of aprotinin as a blood-sparing agent in patients undergoing an elective primary unilateral total hip replacement and to examine its effect on the prevalence of deep-vein thrombosis in this population. METHODS: Seventy-three patients received a placebo; seventy-six patients, a low dose of aprotinin (a load of 500,000 kallikrein inhibitor units [KIU]); seventy-five, a medium dose of aprotinin (a load of 1,000,000 KIU, with infusion of 250,000 KIU per hour); and seventy-seven patients, a high dose of aprotinin (a load of 2,000,000 KIU, with infusion of 500,000 KIU per hour). The end points for the determination of efficacy were transfusion requirements and blood loss. Patients received standard prophylaxis against deep-vein thrombosis and underwent compression ultrasonography with color Doppler imaging of the proximal and distal venous systems of both legs to evaluate for the presence of deep-vein thrombosis. RESULTS: Aprotinin reduced the percentages of patients who required any form of blood transfusion (47 percent of the patients managed with a placebo needed a transfusion compared with 28 percent of those managed with low-dose aprotinin [p = 0.02],27 percent of those managed with high-dose aprotinin [p = 0.008], and 40 percent of those managed with medium-dose aprotinin [p = 0.5]). Only 6 percent (twelve) of the 212 patients treated with aprotinin required allogeneic blood compared with 15 percent (ten) of the sixty-eight patients treated with the placebo (p = 0.03). Aprotinin decreased the estimated intraoperative blood loss (p = 0.02 for the low-dose group, p = 0.04 for the medium-dose group, and p = 0.1 for the high-dose group), the measured postoperative drainage volume (p = 0.4 for the low-dose group, p = 0.006 for the medium-dose group, and p = 0.000 for the high-dose group), and the mean reduction in the hemoglobin level on the second postoperative day (thirty-four grams per liter for the placebo group, twenty-eight grams per liter for the low-dose group [p = 0.000], twenty-six grams per liter for the medium-dose group [p = 0.000], and twenty-three grams per liter for the high-dose group [p = 0.0001). The rate of deep-vein thrombosis was similar for all groups. CONCLUSIONS: We concluded that aprotinin is safe and effective for use as a hemostatic agent in primary unilateral total hip replacements. In patients who are at high risk of receiving allogeneic blood, use of aprotinin may be of particular clinical and economic benefit.     

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery

BACKGROUND: Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS: With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS: There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS: Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.     

Aminocaproic Acid (Amicar) as an Alternative to Aprotinin (Trasylol) in Liver Transplantation

Introduction

This study compared clinical outcomes for a large number of liver transplant patients receiving intraoperative epsilon-aminocaproic acid (EACA), aprotinin, or no antifibrinolytic agent over an 8-year period.

Patients and Methods

Records for deceased donor liver transplants were reviewed. Data included antifibrinolytic agent, blood loss, early graft function, and postoperative complications. Study groups included low-dose aprotinin, high-dose aprotinin, EACA (25 mg/kg, 1-hour infusion), or no antifibrinolytic agent.

Results

Data were included for 1170 consecutive transplants. Groups included low-dose aprotinin (n = 324 [28%]), high-dose aprotinin (n = 308 [26%]), EACA (n = 216 [18%]), or no antifibrinolytic (n = 322 [28%]). EACA had the lowest intraoperative blood loss and required the fewest transfusions of plasma. Patients receiving no agent required the most blood transfusions. Early graft loss was lowest in the EACA group, and 90-day and 1-year patient survival rates were significantly higher for the low-dose aprotinin and EACA groups according to Cox regression. Complications were similar, but there were more episodes of deep vein thrombosis in patients receiving EACA.

Conclusions

These results suggest that transitioning from aprotinin to EACA did not result in worse outcomes. In addition to decreased intraoperative blood loss, a trend toward improved graft and patient survival was seen in patients receiving EACA.     

Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study

Objective: Bleeding complications have been a major concern in certain thoracic surgery operations, especially decortication and pulmonary resection for inflammatory pulmonary infection. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood consumption. Methods: Use of blood products (packed red cells, whole blood), chest tube drainage, analgesic requirement, chest tube duration for the patients undergoing major thoracic operations were recorded. In a double blind randomized fashion, patients were assigned to two groups receiving aprotinin (n=51) at a loading dose of 10⁶ kallikrein inhibitory units (KIU) followed by an infusion of the same dose during chest closure or receiving placebo (n=52). On a daily basis, red-cell percentages of total fluid from drainage bottles were recorded and using the blood hematocrit level of the patient of the day before, the corrected value for the patient's blood volume equivalent of daily drainage was calculated. Results: There was a significant reduction in perioperative use of donor blood (0.98±0.92 vs. 0.45±0.32 unit; P=0.0026), and total chest tube drainage (corrected value for the corresponding blood volume) (28.2±36.9 vs. 76.9±53.3 ml, P=0.0004) (mean±standard deviation) in the aprotinin group. However, aprotinin did not reduce postoperative transfusion or decrease in hematocrit level due to thoracic operations. In high transfusion-risk thoracic surgery patients (patients who underwent decortication, pulmonary resection for inflammatory lung disease and chest wall resection), the perioperative transfusion was only 0.50±1.08 units in aprotinin group, compared with 1.94±0.52 units in control group (P=0.003). Postoperative transfusion was also reduced in aprotinin administrated group (0.53±0.56 vs. 1.38±0.97 units; P=0.02). The mean total blood loss was decreased to nearly one third of the blood loss of the control group (41±28 ml vs. 121±68 ml; P=0.001). Conclusion: Aprotinin significantly reduced perioperative transfusion requirement and postoperative bleeding during major thoracic operations. Aprotinin decreased perioperative transfusion needs. Moreover, patients who were at risk of greater blood loss during and after certain thoracic operations had a greater potential to benefit from prophylactic perioperative aprotinin treatment.     

Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion.

Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements.     

Epsilon-aminocaproic acid in coronary artery bypass graft surgery: preincision or postheparin?

BACKGROUND: Epsilon-aminocaproic acid (epsilon-ACA), an antifibrinolytic agent, is used in cardiac surgery to decrease postoperative bleeding. Theoretical concerns exist about the potential for epsilon-ACA to contribute to thrombotic complications. For this reason epsilon-ACA administration is sometimes delayed until after heparinization. This study investigated the impact of the timing of epsilon-ACA administration on its efficacy. METHODS: In this double-blind study, 90 patients undergoing primary coronary artery bypass graft surgery were prospectively randomized to receive either epsilon-ACA commencing prior to skin incision (bolus 150 mg/kg, followed by an infusion at 15 mg x kg(-1) x hr(-1), epsilon-ACA commencing after heparin (same doses), or placebo. All infusions were terminated at the end of cardiopulmonary bypass. Criteria for the transfusion of blood products were standardized. Postoperative chest tube drainage (at 6 h, 12 h, and at chest tube removal) and blood transfusion requirements of the three groups were compared. RESULTS: At all time intervals, the placebo group had significantly greater chest tube drainage than either of the two epsilon-ACA groups (P < 0.005). At no time did a significant difference exist between the two epsilon-ACA groups. A trend existed for the placebo group to require more blood products than either epsilon-ACA group. CONCLUSIONS: Epsilon-ACA produces a reduction in chest tube drainage in patients undergoing primary coronary artery bypass graft surgery. This effect is similar whether the drug is given prior to incision or following anticoagulation. Given the similar hemostatic efficacy and the theoretical potential for thrombotic complications, it may be prudent to administer epsilon-ACA following anticoagulation.     

Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion.

Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion. IMPLICATIONS: In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion.     

Randomized, Placebo-Controlled, Double-Blind Study of an Ultra-Low-Dose Aprotinin Regimen in Reoperative and/or Complex Cardiac Operations

A bstract Background and aim of the study : High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population. Methods : Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared. Results : Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06). Conclusions : Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products.     

Reduction of blood loss and transfusion requirements after coronary artery bypass grafting: similar efficacy of tranexamic acid and aprotinin in aspirin-treated patients

BACKGROUND: In patients with coronary artery disease, continuation of aspirin may reduce the incidence of unstable angina and preoperative myocardial infarction before surgery, but the risk of perioperative bleeding may be increased. METHODS: The efficacy of aprotinin and tranexamic acid (TXA) was examined in a prospective, randomized, double-blind trial involving 56 patients scheduled for coronary artery bypass grafting and who received aspirin 100 mg/day until the day of the operation. Group I received high-dose aprotinin whereas group II received 10 g of tranexamic acid (TXA) over 20 minutes before sternotomy. Heparinization during cardiopulmonary bypass was controlled with HDTT (high-dose thrombin time) to eliminate interference of aprotinin on ACT (celite activated clotting time). Postoperative blood loss and transfusion requirements were registered during the first 24 hours. RESULTS: The demographics, coagulation, and intraoperative parameters were similar in both groups. Postoperative blood loss (aprotinin 840 mL /24 hours, TXA 880 mL/24 hours, p = 0.481), and transfusion requirements (2.18 units/patient in the aprotinin group, 2.11 units/patient in the TXA group) were not remarkably different between the two regimen protocols. No perioperative myocardial infarction, pulmonary embolism, cerebrovascular event, or other thrombotic events were observed. CONCLUSIONS: In this trial, we were not able to demonstrate any difference in postoperative bleeding in patients pretreated with aspirin after high-dose aprotinin or TXA. From a practical point of view, TXA is safe, less expensive than aprotinin, and easy to handle, and can be recommended in patients pretreated with aspirin to improve postoperative hemostasis.     

Low-dose aspirin protects against lipid accumulation in primate vein bypass grafts

Platelet inhibition with high-dose aspirin combined with dipyridamole reduces lipid accumulation and improves early patency of coronary artery bypass grafts. However, recent evidence suggests that platelet inhibition can be achieved with substantially lower aspirin doses than have been conventionally prescribed. To evaluate whether low-dose aspirin protects against lipid accumulation in bypass grafts, we studied 15 stump-tailed macaque monkeys in which autologous cephalic veins were grafted into the femoral arteries. A control group received no treatment, a second group was treated with a low, single daily dose of aspirin (12 mg), and a third group was given a higher dosage of aspirin (80 mg/day) combined with dipyridamole (50 mg/day) divided into two daily doses. A special diet was fed that resulted in plasma cholesterol levels (224 +/- 50 mg/dl, mean +/- standard deviation) and plasma lipoprotein distributions that mimic the profile in humans. Cholesterol concentration in grafts removed 3 months after insertion was 0.47 +/- 0.12 mg/100 mg tissue in the control group; it was reduced to 0.23 +/- 0.04 mg/100 mg (p less than 0.001) by low-dose aspirin and to 0.17 +/- 0.05 mg/100 mg (p less than 0.001) by combined aspirin and dipyridamole therapy. Graft apolipoprotein B concentration was 66 +/- 19 micrograms/100 mg in control group; it was reduced to 40 +/- 8 micrograms/100 mg (p less than 0.05) by low-dose aspirin and to 23 +/- 7 micrograms/100 mg (p less than 0.001) with the combination treatment. There were no differences between groups in either cholesterol concentration (0.09 +/- 0.02 mg/100 mg) or apolipoprotein B concentration (10 +/- 3 micrograms/100 mg) in normal ungrafted vein. Platelet function tests demonstrated platelet aggregation in all control monkeys, in none of the combined therapy group, and in two of five monkeys receiving low-dose aspirin. This study indicates that low-dose aspirin is protective against graft lipid accumulation in monkeys. The mechanism of this antilipid effect and its relation to any antithrombotic effect remain to be elucidated.     

Postoperatively administered aprotinin or epsilon aminocaproic acid after cardiopulmonary bypass has limited benefit

BACKGROUND: Intraoperative antifibrinolytic treatment with aprotinin and epsilon aminocaproic acid (EACA) has been shown to be effective prophylaxis in the reduction of excessive bleeding after cardiopulmonary bypass operations. This study investigated the effectiveness of both drugs when used as a postoperative treatment of patients showing early signs of increased bleeding. METHODS: In a double-blind, randomized study, 69 patients with chest drainage of 100 mL or more 1 hour after bypass were treated with aprotinin, EACA, or placebo. RESULTS: In the first 24 hours postoperatively, neither drug significantly reduced chest drainage or blood transfusion requirements compared with placebo. Median (interquartile) cumulative chest drainage volumes for the first 24 hours postoperatively for the aprotinin, EACA, and placebo groups were 525 (340, 750), 575 (450, 762), and 650 (550, 800) mL, respectively. Among the study patients, 4 undergoing valve operation and treated with aprotinin showed a trend toward less bleeding during the first 12 hours postoperatively compared with 5 valve operation patients who received placebo (p = 0.06). Among all patients, the treatment with aprotinin or EACA failed to reduce levels of D-dimer compared with placebo after treatment, indicating that fibrinolysis was not significantly inhibited. CONCLUSIONS: Aprotinin or EACA administered in the early postoperative period was ineffective in reducing postoperative bleeding with the exception of a small group of patients having valve operations in whom aprotinin treatment may have shown some benefit.     

Relation of preoperative use of aspirin to increased mediastinal blood loss after coronary artery bypass graft surgery.

To evaluate the potential effect of aspirin, a platelet inhibitory agent, on postoperative bleeding complications after coronary artery bypass graft surgery, we compared each of nine patients who had taken aspirin within 7 days prior to operation to one or two control subjects (total 16 patients) matched for age, sex, extent of coronary disease, number of grafts placed total operative time, bypass time, and preoperative use of propranolol. Preoperative prothrombin time, partial thromboplastin time, and platelet counts were normal for all patients. Mean mediastinal blood loss was significantly greater in the aspirin group (919 +/- 164 ml., S.E.) than in the control group (437 +/- 61 ml., p less than 0.001). The degree of mediastinal blood loss did not correlate with patient age, total operative time, bypass time, number of vessels diseased, or grafts placed. In addition, compared to controls the aspirin group required prolonged chest tube drainage (33 +/- 5 hours versus 19 +/- 1 hour, p less than 0.001).     

Comparative evaluation of the effects of tranexamic acid and low-dose aprotinin on post-valvular heart surgery bleeding and allogenic transfusion

Bleeding diathesis and allogenic transfusion after complex heart surgery, such as heart valve surgery, may result in complications such as transfusion reaction, viral infection, postoperative infection, haemodynamic disturbance, prolonged stay in the intensive care unit and hospital, renal and respiratory failure and mortality. In this prospective, double-blind, randomized, placebo-controlled clinical trial, 90 patients were randomly divided into three groups: aprotinin, tranexamic acid and control. Chest-tube drainage, transfusion requirements and renal and neurological complications were evaluated. We found that chest-tube drainage during the first (P < 0.0001) and second 24 h (P = 0.001) after admission to the intensive care unit were significantly lower in the aprotinin group. The amounts of transfused packed red blood cells (P < 0.0001) and platelets (P = 0.02) were significantly lower in the aprotinin and tranexamic acid groups. The quantity of transfused fresh frozen plasma (P = 0.034) was significantly lower in the aprotinin group only. We did not find any neurological complications or renal failure in the three groups. Our data suggest that in valvular heart surgery, low-dose aprotinin is significantly better than tranexamic acid or a placebo for reduction of postoperative bleeding and allogenic transfusion, without increasing adverse outcomes.     

A prospective study of aspirin's effect on red blood cell loss in cardiac surgery

The effect of aspirin on red blood cell (RBC) loss and blood transfusions was evaluated prospectively in 100 consecutive patients, with normal bleeding times, undergoing elective coronary artery bypass (CABG) surgery. Patients taking 85-325 mgm of aspirin daily up to or within 48 hours of surgery (the "aspirin" group) were compared to patients not taking aspirin or those who had discontinued aspirin at least 4 days before surgery (the "no-aspirin" group). RBC loss was determined by measuring preoperative and postoperative RBC volume using RISA and 51Cr techniques. There were no significant differences, respectively, between the aspirin and no-aspirin groups for: RBC loss (1158 +/- 67 ml vs 1129 +/- 47 ml, p = 0.737), chest tube drainage (925 +/- 31 ml vs 844 +/- 70 ml, p = 0.553), and gm% discharge Hemoglobin (Hgb) (9.94 +/- 0.32 vs 9.49 +/- 1.4, p = 0.0148). Strict criteria for blood transfusions were employed: (1) intraoperative hematocrit of less than 21%, (2) postoperative Hgb of less than 7 gm% for patients less than 70 years old and (3) postoperative Hgb of less than 8 gm% for patients greater than 70 years old. There were no significant differences, respectively, between the aspirin and no-aspirin groups for units of blood transfused (1.32 +/- vs 1.21 +/- 0.20, p = 0.843) and patients not receiving transfusions during the entire hospitalization (44% vs 50%). Patients taking 85-325 mgm of aspirin with a normal bleeding time undergoing elective CABG did not have increased RBC loss or increased transfusion requirements. These results indicate it is not necessary to delay elective CABG surgery for the purpose of discontinuing aspirin.     

Does 111indium-platelet deposition predict patency in prosthetic arterial grafts?

The relationship between the rate of 111In-platelet deposition on vascular grafts and subsequent thrombosis has been examined in patients undergoing femoropopliteal by-pass. Sixty-seven patients undergoing femoropopliteal by-pass using vein, Dacron or PTFE were randomized to aspirin plus dipyridamole (ASA/DPM) or placebo. Autologous 111In-platelets were injected in the second postoperative week and Thrombogenicity Index (TI) calculated as the mean daily rise in the ratio of radioactivity graft/contralateral thigh. Graft patency was assessed to 1 year. Mean (+s.e.m.) TI at 1 week in 21 grafts that occluded within 12 months was 0.19 +/- 0.018 compared with 0.07 +/- 0.009 in the 38 that remained patient (P less than 0.001). Grafts with a TI less or greater than the median had a 90 per cent or 39 per cent cumulative 1-year patency, respectively (P less than 0.001). In the prosthetic grafts ASA/DPM reduced mean TI from 0.17 +/- 0.02 to 0.11 +/- 0.01 (P less than 0.02) and enhanced 1-year patency from 36 to 67 per cent (P less than 0.05). Following femoropopliteal by-pass TI related to subsequent graft patency. Radiolabelled platelet deposition therefore provides a guide as to how new materials or antithrombotic drugs may influence clinical graft thrombosis. Platelet inhibition reduced both graft thrombogenicity and subsequent occlusion.     

High-dose aprotinin in cardiac surgery: is high-dose high enough? An analysis of 8281 cardiac surgical patients treated with aprotinin

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 < 0.001). The proportion of patients requiring allogeneic blood transfusion was reduced from 55% to 47% comparing the lowest with the highest dosing group (P < 0.01). Aprotinin dose was also an independent predictor for rethoracotomy for surgical hemostasis (1.9% in the highest quartile to 2.4% in the lowest dosing quartile; P < 0.01). The risk of renal failure requiring dialysis (2.3% in the highest dosing group vs 3.3% in the lowest dosing group; P < 0.01) or impairment of renal function (creatinine increase of >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.     

Efficacy of aprotinin in children undergoing craniofacial surgery

OBJECT: This prospective, randomized, placebo-controlled, double-blind trial was undertaken to assess the efficacy of aprotinin in reducing the need for blood transfusions in 39 children undergoing reconstructive craniofacial surgery. METHODS: Two demographically similar groups--a total of 39 patients with a mean age of 1.2 +/- 1.2 years--were studied. The efficacy of aprotinin (240 mg/m2 administered intravenously over 20 minutes, followed by infusions of 56 mg/m2/hr) was compared with that of an equal infusion of 0.9% saline (placebo). Patients in the aprotinin group received less blood per kilogram of body weight than patients in the placebo group (32 +/- 25 ml/kg compared with 52 +/- 34 m/kg, respectively; p = 0.04). Those patients in whom aprotinin was administered experienced less change in their hematocrit levels during surgery (aprotinin -33 +/- 13% compared with placebo -44 +/- 9%, p = 0.01). Each patient underwent a transfusion as per study protocol, and there was no significant change in hematocrit levels from the beginning to the end of surgery. The surgical faculty judged blood loss in patients in the aprotinin group to be significantly less than usual (p = 0.03). The use of aprotinin was also associated with reduced blood transfusion requirements during the first 3 postoperative days (p = 0.03). There was no adverse event reported in either the aprotinin or placebo group. CONCLUSIONS: Aprotinin decreased blood transfusion requirements in pediatric patients undergoing craniofacial reconstruction, thereby reducing the risks associated with exposure to banked blood components.