Blood coagulation and autologous blood transfusion in cardiac surgery

Study Objective: To review the basic pathophysiology of altered coagulation associated with cardiopulmonary bypass and autologous blood transfusion in cardiac surgery.

Design: Review of rational use of heparin, mechanisms and treatment of coagulation disorders, and autologous blood transfusion.

Setting: Cardiac surgery in community and academic hospitals.

Patients: Adult cardiac surgical patients.

Main Results: Heparin is most commonly used for anticoagulation during cardiopulmonary bypass. Although activated clotting time is widely used to assess heparin-induced anticoagulation, the minimum time to prevent clotting during cardiopulmonary bypass remains unclear. Activated clotting time is affected by many factors other than heparin, such as antithrombin III, blood temperature, platelet count, and age. The rational use of activated clotting time still must be defined.

The frequency of abnormal bleeding after cardiopulmonary bypass is significant. Although inadequate surgical hemostasis is the most frequent cause of bleeding, altered coagulation often is present. A decreased number of functional platelets is one of the important causes of bleeding diathesis. Platelet dysfunction is induced by perioperative medication such as aspirin. Cardiopulmonary bypass decreases functional platelets by degranulation, fragmentation, and loss of fibrinogen receptors. Medications such as prostacyclin and iloprost may be useful to protect these platelets. Desmopressin increases factor VIII:C and von Willebrand's factor, leading to a decrease in bleeding time. Desmopressin may be useful to decrease blood loss in repeat cardiac operations, complex cardiac surgery, and abnormal postoperative bleeding.

Patients undergoing coronary artery bypass grafting immediately after streptokinase infusion also are at risk for abnormal bleeding. Transfusion of fresh frozen plasma and cryoprecipitate may be necessary.

Autologous blood transfusion is cost-effective and the safest way to avoid or decrease homologous blood transfusion. Predonation, intraoperative salvage, and postoperative salvage are encouraged. Erthroprotein may be useful in increasing the amount of predonation red cells.

Conclusions: Coagulation disorders in cardiac surgery are caused by many factors, such as heparin, platelet dysfunction, and fibronolysis. Rational use of blood component therapy and medications such as heparin, protamine, and desmorpessin are mandatory. Autologous blood transfusions is very useful in decreasing or obviating the use of homologous blood transfusion.     

Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations

Background. Desmopressin (DDAVP) has been evaluated in many randomized clinical trials as a means to reduce blood loss and transfusion of allogeneic blood in cardiac operation requiring cardiopulmonary bypass. Desmopressin reduces blood loss in adult patients with excessive bleeding after cardiac operation. Its usefulness in patients undergoing complex congenital heart repair with cardiopulmonary bypass is unproved.

Methods. Sixty patients younger than 40 years of age scheduled for complex congenital heart operation (44 redo, 16 primary) were enrolled in this prospective, randomized, double-blind trial. Desmopressin 0.3 μg/kg or placebo was administered 10 minutes after protamine administration. Transfusion requirements and postoperative blood loss were recorded. Differences were analyzed using analysis of variance with a p value of 0.05 or less used to denote statistical significance.

Results. There were no differences in demographic or surgical characteristics between the DDAVP or placebo groups. There was no difference in blood loss and transfusion requirements between the DDAVP and placebo groups. During the intraoperative postinfusion time period, the median blood loss for redo patients was 343 versus 357 mL/m² for placebo versus DDAVP, respectively, and for primary patients, the median blood loss was 277 versus 228 mL/m².

Conclusions. The prophylactic use of DDAVP to reduce excessive bleeding or transfusion requirements in patients undergoing complex congenital heart operations is not warranted.     

Is transfusion of fresh plasma after cardiac operations indicated?

Patients undergoing cardiac operations constitute the majority of recipients of fresh frozen plasma. In most centers the reason for transfusing fresh frozen plasma is to replace clotting factors. However, the decrease of clotting factors during cardiopulmonary bypass is not sufficient in most patients to cause abnormal bleeding. One of the major causes of nonsurgical bleeding after cardiac operations is acquired platelet dysfunction, which can be corrected by transfusion of 1 unit of fresh whole blood. Because plasmatic factors in fresh whole blood may be responsible for this improvement, a study was designated to evaluate the effect of transfusing fresh plasma on platelet function after cardiac operations. Forty patients undergoing cardiopulmonary bypass were randomized to receive either fresh plasma or the fresh packed cell fraction. Administration of packed cells increased platelet number (118 +/- 8.5 to 154 +/- 7.6 x 10(9)/L, p less than 0.05), shortened bleeding time (7.57 +/- 0.4 to 4.0 +/- 0.3 minutes, p less than 0.05), and improved platelet aggregation in response to collagen and epinephrine (32% +/- 4.7% to 50% +/- 5.6% and 37% +/- 5.8% to 50% +/- 5.8%, respectively, p less than 0.05). Fresh plasma, however, neither increased platelet number nor improved bleeding time or platelet aggregation. Each group later received the remainder of the blood unit, with similar results. The results suggest that improvement of platelet function in patients receiving fresh whole blood after cardiac operations is not related to plasmatic factors. Therefore the massive use of fresh frozen plasma in patients after cardiopulmonary bypass should be reconsidered.     

Reduction in Requirements for Allogeneic Blood Products: Pharmacologic Methods

Background. Numerous articles describe the reduction of perioperative bleeding by the therapeutic or prophylactic administration of drugs such as prostacyclin, desmopressin, and natural or synthetic antifibrinolytics.

Methods. A review of the literature was carried out to help the reader define the indications of these drugs during cardiopulmonary bypass operations, highlight the questions that remain concerning their indications and modes of action, and suggest future studies to answer these remaining questions.

Results. Prostacyclin reduces platelet trauma induced by extracorporeal circulation but does not effectively reduce postoperative bleeding and transfusion requirements. Desmospressin acts as a “glue,” improving platelet adhesion, and may be effective when postoperative bleeding is excessive, but its routine use in cardiac operations cannot be recommended. Natural and synthetic antifibrinolytics inhibit plasmin and plasmin-induced platelet dysfunction. These agents have been shown to decrease bleeding and the need for allogeneic transfusions after open heart operations. However, with antifibrinolytic drugs, the risk of thromboembolic phenomena cannot be neglected. With aprotinin, this risk appears to be minimal when the drug is used at concentrations high enough to inhibit plasma kallikrein also.

Conclusions. Prophylactic antifibrinolytics are efficacious, but their routine use remains controversial, both for economic reasons and for fear of thromboembolic complications.     

Treatment of Excessive Mediastinal Bleeding After Cardiopulmonary Bypass

Background. Excessive mediastinal bleeding after cardiopulmonary bypass is one of the most frequently reported complications of cardiac operations. Appropriate treatment requires a rapid and effective diagnostic work-up, based on the knowledge of the pathophysiology induced by cardiopulmonary bypass.

Methods. Possible causes, diagnostic methods available, and therapeutic approaches are reviewed in the light of the literature published on excessive bleeding after cardiac operations.

Results. When bleeding is massive (>250 to 300 mL/h for the first 2 hours, >150 mL/h thereafter), immediate surgical reexploration is mandatory. When bleeding is less important (50 to 150 mL/h), the decision to reoperate should be based on the presence of hemodynamic compromise or a suspected surgical cause. Otherwise, coagulation testing should allow the correction of hemostatic defects as appropriate with protamine, platelet concentrates, fresh frozen plasma, desmopressin, or antifibrinolytics. Hypothermia and hypotension should be corrected and a trial of positive end-expiratory pressure may be considered if diffuse mediastinal oozing (especially from the bed of the mammary artery) is suspected.

Conclusions. A protocol is suggested to guide treatment, taking into account the rapidity of blood loss and the suspected underlying cause.     

Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery

OBJECTIVES: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. METHODS: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU.kg(-1).h(-1) continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (<10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. RESULTS: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r =.57, P =.003; r =.69, P =.001, respectively). CONCLUSION: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.     

Risk factors reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum assisted circuits

OBJECTIVES: Open heart surgery without homologous blood transfusion remains difficult in children. The introduction of vacuum-assisted cardiopulmonary bypass circuits to reduce priming volume for pediatric patients has improved the percentage of transfusion-free operations. We retrospectively analyzed blood transfusion risk factors to further reduce blood transfusion requirements after vacuum-assisted circuit introduction. METHODS: From March 1995 to June 1996, 49 patients weighing between 5 and 20 kg underwent cardiac surgery with cardiopulmonary bypass at our institution, excluding hospital deaths. We retrospectively analyzed risk factors influencing blood use in 37 patients with no blood priming in cardiopulmonary bypass after introducing a vacuum-assisted system. Factors selected for univariate analysis were age, body weight, cyanosis, preoperative Hb, operation time, cardiopulmonary bypass time, aortic cross-clamping time, and intraoperative and postoperative bleeding volume. Correlation between total bleeding volume/body weight and cardiopulmonary bypass time was studied by regression analysis. RESULTS: As risk factors, univariate analysis identified cyanotic disease, longer operation time (> 210 minutes), longer cardiopulmonary bypass time (> 90 minutes), longer aortic cross-clamping time (> 45 minutes), greater intraoperative bleeding volume/body weight (> 4 ml/kg), and greater postoperative bleeding volume/body weight (> 15 ml/kg). Regression analysis showed a significant positive correlation between total bleeding volume/body weight and cardiopulmonary bypass time. CONCLUSIONS: Cyanotic disease and long bypass time are risk factors in reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum-assisted circuits. Further efforts are needed, however, to reduce blood transfusion requirements, particularly in these children.     

小剂量抑肽酶结合自体输血对体外循环围术期凝血和纤溶功能的影响

目的：观察小剂量抑肽酶加自体输血对体外循环围术期凝血和纤溶功能的影响。方法：２０例体外循环心脏直视手术病人，分为抑肽酶＋自体输血组（Ａ组）和对照组（Ｃ组），连续监测围术期凝血及纤溶功能的变化。结果：Ａ组病人在术中及术后ＰＡｇＴ、ＰＬＧ、α２－ＡＰ等均显著高于Ｃ组，（Ｐ＜０．０５或０．０１），而Ｄ－Ｄ却显著低于Ｃ组（Ｐ＜０．０１）。Ａ组病人术后出血量和输血量均显著少于Ｃ组（Ｐ＜０．０１）。结论：小剂量抑肽酶＋自体输血能显著减轻体外循环引起的凝血功能紊乱，预防和减轻继发纤溶亢进，从而显著减少了术后出血和输血量。     

Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?

Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well‐designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ?‐aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high‐dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ?‐aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays.     

Heparin-induced platelet dysfunction and cardiopulmonary bypass

Background. Cardiopulmonary bypass is associated with impaired platelet macroaggregation. Heparin contributes to platelet dysfunction before extracorporeal circulation. In vitro heparinization of whole blood does not impair macroaggregation. Heparin releases several endothelial proteins; thus heparin may inhibit macroaggregation indirectly.

Methods. Patients undergoing operations using cardiopulmonary bypass and ABO blood group compatible volunteers were studied. Whole blood impedance aggregometry assessed macroaggregation in response to collagen (0.6 μg ml⁻¹) in blood diluted either with normal saline or with platelet poor plasma, obtained from patients at different stages of cardiopulmonary bypass.

Results. Before heparinization, blood diluted with its own platelet poor plasma recorded an impedance change of 13.0 (4.7 to 15.6) Ohms. Platelet poor plasma obtained after heparinization or during extracorporeal circulation reduced this response to 3.7 (1.1 to 8.4) and 2.0 (1.1 to 3.3) Ohms, respectively (both p < 0.0001 versus pre-heparin; n = 13). Macroaggregation in blood from volunteers was similarly inhibited by patients’ platelet poor plasma (n = 30). The macroaggregatory response in blood sampled after heparinization for cardiopulmonary bypass, decreased gradually from 11.4 (8.2 to 15.9) Ohms immediately after sampling to 1.7 (1.4 to 4.1) Ohms 2 hours later (p < 0.0001; n = 11).

Conclusions. In vivo heparinization induces plasma changes that inhibit platelet macroaggregation. This is an indirect, delayed inhibition that is transferable in vitro to normal platelets.     

The use of aprotinin in pediatric patients: a review

This literature review includes all reports from 1993 to 2000 concerning the use of aprotinin in children undergoing cardiopulmonary bypass (CPB) for congenital cardiac surgery. This review examined a nonhomogeneous pediatric patient population ranging from neonates to children up to 18 years of age, presenting many challenges. There have been publications advocating its use and those that have found no significant difference between the control group and those receiving aprotinin. The literature suggests that there is improvement in post-operative blood loss in pediatric patients undergoing redo cardiac surgery, but no significant difference in blood loss in those undergoing primary surgical repair. There is some evidence in the neonatal study groups that with high-dose aprotinin the inflammatory response is attenuated, leading to a reduction in inotropic support, earlier extubation, a tendency toward reduced post-operative blood loss and a reduced hospital stay. In most of the studies, the actual dose of aprotinin has varied with "high-dose aprotinin" demonstrating the most significant differences. To achieve an adequate dose of aprotinin, the dose must be calculated on either the patient's weight or their body surface area, and must include an appropriate dose in the prime of the cardiopulmonary bypass circuit, to achieve a plasma concentration between 200 KIU/mL to 400 KIU/mL. The incidence of anaphylactic reactions reported in the literature range from 0.3 to 0.6%. To date, there is no evidence to indicate any contraindication related to the use of aprotinin in the pediatric population.     

Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.     

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.     

Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

A trial of fresh autologous whole blood to treat dilutional coagulopathy following cardiopulmonary bypass in infants

BACKGROUND: Transfusion of fresh whole blood is superior to blood component therapy in correcting coagulopathies in children following cardiopulmonary bypass (CPB); however, a supply of fresh homologous whole blood is difficult to maintain. We hypothesized that transfusion of fresh autologous whole blood obtained prior to heparinization for CPB and infused following CPB would be associated with improved coagulation function when compared with standard therapy. METHODS: A total of 32 infants 5-12 kg undergoing noncomplex open cardiac surgery were randomly assigned to either the treatment or control group. In the treatment group, 15 ml x kg(-1) of autologous whole blood was collected into a CPDA bag prior to heparinization while 15 ml x kg(-1) of 5% albumin was infused intravenously. After reversal of heparin, coagulation tests were drawn in both groups, and the autologous whole blood was infused over 20 min in the treatment group. RESULTS: The treatment group had greater (P < 0.05) improvement in platelet count, prothrombin time, and fibrinogen than the control group. CONCLUSIONS: We conclude that collection of fresh autologous whole blood prior to heparinization and reinfusion following CPB is associated with greater improvement of coagulation status after CPB in infants.     

Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid,aprotinin or a combination?

BACKGROUND: Children with cyanotic heart disease undergoing cardiac surgery in which cardiopulmonary bypass is used are at increased risk of postoperative bleeding. In this study, the authors investigated the possibility of reducing postoperative blood loss by using aprotinin and tranexamic acid alone or a combination of these two agents. METHODS: In a prospective, randomized, blind study, 100 children undergoing cardiac surgery were investigated. In group 1 (n = 25) patients acted as the control and did not receive either study drugs. In group 2 (n = 25) patients received aprotinin (30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25) patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia, 100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In group 4 (n = 25) patients received a combination of the two agents in the same manner. Total blood loss and transfusion requirements during the period from protamine administration until 24 h after admission to the intensive care unit were recorded. In addition, hemoglobin, platelet counts and coagulation studies were recorded. RESULTS: Postoperative blood loss was significantly higher in the control group (group 1) compared with children in other groups who were treated with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3 and 4) during the first 24 h after admission to cardiac intensive care unit (40 +/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)). The total transfusion requirements were also significantly less in the all treatment groups. Time taken for sternal closure was longer in the control group (68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/- 18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not found to be significantly different between the three groups. CONCLUSIONS: Our results suggested that both agents were effective to reduce postoperative blood loss and transfusion requirements in patients with cyanotic congenital heart disease. However, the combination of aprotinin and tranexamic acid did not seem more effective than either of the two drugs alone.     

Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin

Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk = 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.     

Granulocyte Phagocytic Function Is Impaired During Cardiopulmonary Bypass

Background. The presence of impaired phagocytic function of the reticuloendothelial system after cardiac operations using cardiopulmonary bypass remains controversial.

Methods. In this study, the phagocytic function of granulocytes in 14 patients undergoing cardiac operations with cardiopulmonary bypass was examined using a chemiluminescence method. Seven patients with abdominal aortic aneurysms served as controls. Electron microscopy also was employed to evaluate morphologic changes.

Results. The 14 cardiac patients showed impaired phagocytic function from immediately after operation until 12 hours after the operation. This phagocytic function recovered within 24 hours. The 7 control patients showed no change in phagocytic function during or after the operation. Scanning electron microscopic examination of the cardiac patients' granulocytes revealed the loss of villi on cell surfaces immediately after operation. However, these villi were restored within 24 hours after the operation.

Conclusions. The phagocytic function of granulocytes was impaired in the early postoperative period in patients undergoing cardiopulmonary bypass, and this was probably due to the loss of villi on granulocyte surfaces.     

Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass

BACKGROUND: The pharmacological inhibition of blood-foreign surface interactions is an attractive strategy for reducing the morbidity associated with cardiopulmonary bypass. We compared the inhibitory effects of nafamostat mesilate (a broad-spectrum synthetic protease inhibitor) and minimal-dose aprotinin on blood-surface interactions in clinical cardiopulmonary bypass. METHODS: Eighteen patients undergoing coronary surgery were divided into three groups: (1) the control group (heparin, 4 mg/kg; n = 6), (2) the nafamostat mesilate group (heparin plus nafamostat, 0.2 mg/kg bolus followed by 2.0 mg/kg/h during cardiopulmonary bypass; n = 6), and (3) the aprotinin group (heparin plus aprotinin, 2.0 x 10(4) KIU/kg; n = 6). Platelet count, platelet aggregation, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, plasminogen activator inhibitor-1, alpha2-plasmin inhibitor-plasmin complex, D-dimer, neutrophil elastase, and interleukin-6 were measured before, during, and after bypass. Bleeding times and blood loss were recorded. RESULTS: There were no significant differences between groups in platelet count, beta-thromboglobulin, plasminogen activator inhibitor-1, interleukin-6, bleeding times, or blood loss. Platelet aggregation was better preserved at 12 hours after surgery in the nafamostat and aprotinin groups than in the control group. Prothrombin fragment F1.2, thrombin-antithrombin complex and neutrophil elastase levels were significantly reduced by aprotinin, but not by nafamostat as compared with the control group. The alpha2-plasmin inhibitor-plasmin complex and D-dimer were significantly lower with either of the drugs. Aprotinin showed better control of D-dimer than did nafamostat. CONCLUSIONS: Nafamostat mesilate fails to reduce thrombin formation and neutrophil elastase release, whereas minimal-dose aprotinin inhibits both. Neither nafamostat nor aprotinin inhibits platelet activation. Nafamostat reduces fibrinolysis during cardiopulmonary bypass, although its effect is not as potent as aprotinin.     

High‐dose aprotinin,blood product transfusions,and short‐term outcome in neonates and infants: a pediatric cardiac surgery center experience

Background: The efficacy of aprotinin, the most popular antifibrinolytic agent in congenital cardiac surgery, was still uncertain in small infants when its prophylactic use was suspended for safety reasons. The aim of this study is to describe associations between the prophylactic use of high‐dose aprotinin, the need for blood product transfusions, and short‐term outcome in neonates and infants with cardiac surgery. Methods/materials: This retrospective study included all patients younger than 1 year undergoing surgery with cardiopulmonary bypass through 42 months, before and after withdrawal of aprotinin. Each patient who received aprotinin was matched with a control with similar baseline and surgical characteristics, who have not received any antifibrinolytic agent. Associations between the use of aprotinin and the exposure to red blood cells, fresh frozen plasma, and platelet transfusions were estimated from a logistic regression model, and the exposure to additional transfusions from a polytomous regression model. Results: Matching resulted in two groups of 283 patients each, well balanced except for the priming volume and the ultrafiltration rate, larger in the aprotinin group. After adjustment for the priming volume and ultrafiltration rate, there was no significant association between the use of aprotinin, the exposure to any blood product transfusion, or the exposure to additional transfusions, the rate of re‐exploration for bleeding, and short‐term outcome. Two patients in the control group required re‐exploration for bleeding. Conclusions: No association was found between the prophylactic use of aprotinin, blood product transfusions, and short‐term outcome in this population of neonates and infants.