Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: baseline values and comparisons

Activation of clotting with tissue factor (TF) allows rapid evaluation of thromboelastograms but alters the values of thromboelastogram variables. We have performed TF-activated thromboelastograms in 250 children <2 yr old undergoing cardiac surgery to establish baseline values. Five groups were distinguished to evaluate the effects of quantitative deficiencies in coagulation factor levels during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of clotting (R and K values) was similar among groups. Infants 1-3 mo of age demonstrated increased clot strength compared with the other groups, a finding similar to previous evaluation of native thromboelastograms. The alpha and maximum amplitude values were numerically almost identical in each age group, a unique finding in activated thromboelastograms. Fibrinolysis was similar among groups. We believe that knowledge of baseline TF-activated thromboelastogram variables in young children will be useful in interpreting these thromboelastograms in clinical scenarios, in using these thromboelastograms as part of coagulopathy treatment algorithms, and during the application of more specific thromboelastogram modifiers. Additionally, the similarity of alpha and maximum amplitude values in each age group will allow even faster interpretation of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor-activated thromboelastograms in young children undergoing cardiac surgery have been established and will permit accurate use and interpretation of this thromboelastogram modification in evaluating and managing coagulopathies.     

Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients.

To determine the clinical usefulness of the thromboelastogram in the prediction of postoperative hemorrhage in cardiac patients, we related the results of routine coagulation tests (RCTs) and thromboelastography with the amount of chest tube drainage postoperatively in 101 patients requiring cardiopulmonary bypass. Our data indicated that there was no correlation between RCT results and thromboelastographic variables. No single variable of RCTs and thromboelastography correlated well with the amount of chest tube drainage postoperatively. Before the onset of cardiopulmonary bypass, the most frequent abnormalities detected by thromboelastograms were fibrinolysis and hypocoagulability resulting from factor deficiency. Hypercoagulability detected by thromboelastograms occurred in 13% of patients after cardiopulmonary bypass and usually was not detected by RCTs. The incidence of false-negative thromboelastograms and RCT results in patients who had excessive hemorrhage of unknown cause was 46% and 52%, respectively. The incidence of fibrinolysis as detected by thromboelastograms was similar before and after bypass, but only 2 of the 18 patients with fibrinolysis had excessive hemorrhage postoperatively. Our results indicate that neither RCTs nor thromboelastography predicts the likelihood of excessive hemorrhage in patients after cardiopulmonary bypass. The thromboelastographic results should be interpreted cautiously because of the high rate of unreliable results.     

Evaluation of post-cardiopulmonary bypass coagulation disorders by differential diagnosis with a multichannel modified thromboelastogram: a pilot investigation.

We assessed a modified multichannel thromboelastogram for differentiation of the causes of coagulopathy after cardiopulmonary bypass and its suitability as a therapy guide. Thirty adult patients undergoing surgery with cardiopulmonary bypass, who revealed a coagulopathy as observed by a prolonged activated clotting time of >150 sec after the application of protamine, were enrolled. Therapy was based on the results obtained by the computerized four-channel thromboelastogram with baseline, heparinase (2 IU/mL), heparinase/abciximab (5 microg/mL), and heparinase/fresh frozen plasma (25%) channels. The mean activated clotting time before therapy was 162.2+/-7.8 sec. Based on differential diagnosis with the modified multichannel thromboelastogram, two patients received protamine (30 mg), five desmopressin (0.4 microg/kg), 19 patients three units of fresh frozen plasma, two patients platelet transfusions, and two patients both protamine (30 mg) and three units of fresh frozen plasma. After therapy, there was a significant (p < .01) decrease of the activated clotting time to a mean value of 127+/-8.3 sec. Therapy based on the synoptic modified multichannel thromboelastogram analysis provides a guide for effective therapy of coagulopathy. However, elaboration is desirable, and larger clinical trials are necessary for a final evaluation of the protocol.     

The Effects of Heparinase 1 and Protamine on Platelet Reactivity

Background: Protamine is currently the most widely used drug for the reversal of heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a possible alternative to protamine for the reversal of heparin anticoagulation. The authors evaluated the effects of equivalent doses of heparinase and protamine on platelet reactivity by measuring agonist-induced P-selectin expression.

Methods: After Institutional Review Board (IRB) approval, informed consent was obtained from 12 healthy volunteers and 8 patients undergoing surgery requiring cardiopulmonary bypass (CPB). Twenty-four ml of blood was obtained from each volunteer; 10 ml of blood was obtained from each patient before the CPB, and another 10 ml was obtained after CPB. Heparin was neutralized using heparinase or protamine. Platelet reactivity was assessed by measuring the expression of P-selectin after stimulation of platelets with increasing concentrations of a thrombin receptor agonist peptide (TRAP). Data were analyzed using analysis of variance. P < 0.05 was considered significant.

Results: For the healthy volunteers, the activated coagulation times (ACTs) of the heparinized samples returned to baseline values with heparinase (12.5 U/ml) or protamine (32.5 micro gram/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20 U/ml) or protamine (50 micro gram/ml). The authors found no difference in the expression of P-selectin in samples neutralized with heparinase, but samples neutralized with protamine showed a significant decrease in the expression of P-selectin when compared with heparinized samples.     

Impact of Sonoclot hemostasis analysis after cardiopulmonary bypass on postoperative hemorrhage in cardiac surgery

Purpose The Sonoclot Analyzer provides a functional test of whole blood coagulation by measuring the viscous property of the blood sample. In this study, we used a modified Sonoclot assay, using cuvettes with a glass bead activator containing heparinase, and compared the Sonoclot data before and after cardiopulmonary bypass (CPB) to assess the usefulness in predicting postoperative hemorrhage. Methods In 41 cardiac surgery patients, Sonoclot data were obtained immediately after heparin administration (pre-bypass) and just before protamine administration (post-bypass). Excessive bleeding was defined as chest tube drainage greater than 2 ml·kg⁻¹·h⁻¹ in 1 h during the first 4 h after surgery. Results There were no significant differences in Sonoclot values before and after CPB in patients with acceptable bleeding (n = 29). In patients with excessive bleeding (n = 12), Sonoclot variables reflecting fibrin formation (activated clotting time [ACT], rate of fibrin formation [clot rate], and peak clot signal) were preserved after CPB; however, the variables reflecting platelet-fibrin interaction (time to peak, peak angle, and clot retraction rate) were significantly different from their respective pre-bypass values. Sonoclot analysis showed impairment of clot maturation after CPB in patients with excessive postoperative bleeding. Conclusion Our results suggest that abnormal postoperative hemorrhage can be predicted by Sonoclot analysis with a new glass bead-activated heparinase test performed after CPB.     

Successful management after cardiopulmonary bypass without administration of protamine in a patient with severe food allergy--beneficial result with the use of heparin-coated bypass circuit

We experienced the anesthetic management for cardiac surgery without the administration of protamine in a patient with severe food allergy. The patient, a 15-year-old boy, who had been avoiding many kinds of food including fish due to severe food allergy, received a correction of ventricular septal defect under cardiopulmonary bypass (CPB). To detect intraoperative drugs, including protamine, which might induce allergic reaction, we performed intradermal tests and prick tests. We used heparin-coated bypass circuit to minimize the amount of heparin necessary for anticoagulation during CPB. After CPB, hemostasis was achieved without the administration of protamine, and the patient received neither transfusion nor blood product throughout the perioperative period. Avoidance of protamine is advisable if the patient is allergic to food especially fish. The use of heparin-coated bypass circuit should be considered to establish hemostasis without protamine after CPB and to reduce blood products.     

Agreements between the prothrombin times of blood treated In Vitro with heparinase during cardiopulmonary bypass (CPB) and blood sampled after CPB and systemic protamine

The prothrombin time (PT) is useful for identifying coagulation factor deficits after cardiopulmonary bypass (CPB). However, long processing times and the need for fresh frozen plasma (FFP) to be thawed cause delays in factor replacement. We hypothesized that, by treating with heparinase, blood sampled toward the end of CPB can provide PT results that help to determine the requirement for FFP after CPB. Laboratory delays can be eliminated with point-of-care monitors. We studied 158 adults undergoing nonemergent cardiac surgery. Blood taken before separation from CPB was mixed with heparinase, and PT was measured in the laboratory with a HemoTec timer. Agreements between these results and laboratory measurements of blood taken after systemic protamine were compared by using Bland and Altman plots with the threshold of +/-1.0 s. We found that the laboratory PT measurements during CPB versus after CPB were compara-ble, but the limits of agreement exceeded these thresholds. Similarly, there was unsatisfactory agreement between the HemoTec and laboratory PT results measured before, during, and after CPB. For each PT measured during CPB, the corresponding confidence interval for the postprotamine PT was calculated. During CPB, a laboratory PT of < or =16 s or > or =18 s suggests a > or =83% or > or =93% probability of not requiring or potentially requiring, respectively, FFP after CPB. We conclude that the majority of PT measurements obtained from blood taken before weaning from CPB and treated in vitro with heparinase was associated with a high probability of whether or not FFP would be needed after CPB. IMPLICATIONS: Coagulation dysfunction after cardiopulmonary bypass may contribute to bleeding. Obtaining coagulation tests and fresh frozen plasma requires time and delays treatment in patients who need fresh frozen plasma. We have devised a technique to provide early estimation of postbypass coagulation status.     

Coagulation tests during cardiopulmonary bypass correlate with blood loss in children undergoing cardiac surgery.

OBJECTIVES: To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage. DESIGN: Prospective. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Four hundred ninety-four children. INTERVENTIONS: Coagulation tests. MEASUREMENTS AND MAIN RESULTS: Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (< or = 108,000/microL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units). CONCLUSIONS: During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.     

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.     

Prediction of excessive bleeding after coronary artery bypass graft surgery: the influence of timing and heparinase on thromboelastography

OBJECTIVE: To compare the ability of thromboelastography, when done at either 10 or 60 minutes after protamine reversal of heparin, to predict excessive bleeding after coronary artery bypass graft (CABG) surgery and to investigate, with the use of heparinase, whether heparin contamination was responsible for the difference, if any. DESIGN: Prospective study. SETTING: University hospital, single institution. PARTICIPANTS: Patients undergoing elective CABG surgery (n = 40). INTERVENTIONS: Blood samples for thromboelastography and routine coagulation tests were collected before induction of anesthesia and at 10 and 60 minutes after protamine reversal of heparin. Blood loss and blood product use were recorded postoperatively. MEASUREMENTS AND MAIN RESULTS: Of 40 patients undergoing elective CABG surgery, 10 fulfilled the criteria for excessive postoperative bleeding. The sensitivity of thromboelastography to identify patients who bled was better at 60 minutes than at 10 minutes after protamine reversal of heparin (100% v 70%). There was greater specificity (83% v 40% at 10 minutes; 73% v 20% at 60 minutes) and positive predictive value (58% v 28% at 10 minutes; 55% v 29% at 60 minutes) when heparinase was added. At both times, thromboelastography showed only moderate correlation with total blood loss and the use of fresh frozen plasma or platelets or both. Conventional coagulation tests did not predict excessive postoperative bleeding. CONCLUSION: This study suggests that timing and the use of heparinase influence the predictive ability of thromboelastography, but its usefulness as a sole predictor of post-CABG surgery bleeding is limited.     

Life threatening cardiopulmonary failure in an infant following protamine reversal of heparin after cardiopulmonary bypass

Life threatening cardiopulmonary failure following protamine reversal of heparin after cardiopulmonary bypass (CPB) was reported to occur in adults but rarely in children. Atrial septal defect closure was performed in a 6-week-old infant erroneously suspected to suffer from right atrial thrombosis in addition. Protamine administration after CPB led to critical pulmonary hypertension and severe haemorrhagic pulmonary oedema resulting in severe hypoxia. Inhaled nitric oxide, together with high frequency oscillation ventilation supplemented by intravenous prostacycline, enabled complete recovery of cardiopulmonary and neurological function. Life threatening cardiovascular compromise after intravenous protamine can occur even in young infants which then require challenging paediatric critical care.     

A prospective, randomized study of cardiopulmonary bypass temperature and blood transfusion

BACKGROUND: We hypothesized that normothermic cardiopulmonary bypass (CPB) would be associated with decreased blood loss and allogeneic transfusion requirements relative to hypothermic CPB. METHODS: After obtaining institutional review board approval and informed patient consent, we conducted a prospective, randomized study of 79 patients undergoing CPB for a primary cardiac operation at normothermic (37 degrees C) (n = 44) or hypothermic temperature (25 degrees C) (n = 35). Blood loss and transfusion requirements in the operating room and for the first 24 hours in the intensive care unit were determined. A paired t test and rank sum tests were used. A p value of less than 0.05 was considered significant. RESULTS: The normothermic and hypothermic CPB groups did not differ in demographic variables, CPB or cross-clamp duration, heparin sodium or protamine sulfate dose, prothrombin time, or thromboelastogram results. There were no differences between the two CPB groups in blood loss or transfusion requirements. CONCLUSIONS: We found that when there was no difference in duration of CPB, normothermic and hypothermic CPB groups demonstrated similar blood loss and transfusion requirements even though other studies have shown hypothermia induces platelet dysfunction and alters the activity of the coagulation cascade.     

The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery

Hemorrhage after cardiopulmonary bypass (CPB) remains a clinical problem. Point-of-care tests to identify hemostatic disturbances at the bedside are desirable. In the present study, we evaluated the predictive value of two point-of-care tests on postoperative bleeding after routine cardiac surgery. Prospectively, 255 consecutive patients were studied to compare the ability of modified thromboelastography (ROTEG) as well as a platelet function analyzer (PFA-100) to predict postoperative blood loss. Measurements were performed at three time points: preoperatively, during CPB, and after protamine administration with three modified thromboelastography and PFA tests. The best predictors of increased bleeding tendency were the tests performed after CPB. The angle alpha is the best predictor (area under the receiver operating characteristic curve 0.69) and, in combination with the adenosine diphosphate-PFA test, the predictive accuracy is enhanced (area under the receiver operating characteristic curve 0.73). The negative predictive value for the angle alpha is 82%, although the positive predictive value is small (41%). Thromboelastography is a better predictor than PFA. In routine cardiac surgery, impaired hemostasis as identified by point-of-care tests does not inevitably lead to hemorrhage postoperatively. However, patients with normal test results are unlikely to bleed for hemostatic reasons. Bleeding in these patients is probably caused surgically. The high negative predictive value supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. IMPLICATIONS: Thrombelastography and platelet function analysis in routine cardiac surgery demonstrate high negative predictive values for postoperative bleeding, which supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. The positive predictive values are small. The best predictors are thrombelastography values obtained after cardiopulmonary bypass.     

Effects of protamine administration after cardiopulmonary bypass on complement, blood elements, and the hemodynamic state

Nineteen patients were prospectively selected and studied before and after the administration of protamine sulfate following cardiopulmonary bypass (CPB). After protamine administration, C3a, C4a, and C4d were elevated; the peak levels of C3a and C4a were in samples taken 10 minutes after protamine administration while those of C4d were in those obtained at 5 hours. Only C3a was elevated after CPB and before protamine administration. In vitro, only the combination of protamine sulfate and heparin, and neither alone, resulted in increased C3a and C4a. Administration of protamine was associated with small and transient decreases in total white blood cells, granulocytes, and platelets, and with small and transient reductions in systemic and pulmonary arterial and left and right atrial pressures. Systemic vascular resistance fell (p = 0.07), and pulmonary vascular resistance rose but the change could be due to chance (p = 0.29). These data and those reported by others support the inference that complement activation occurs during CPB by the alternative pathway and again during protamine administration by the classic pathway; and that this accompanies a whole-body inflammatory reaction with blood cell and hemodynamic changes which, when extreme, could result in a severe hemodynamic derangement.     

Heparinase in the activated clotting time assay: monitoring heparin-independent alterations in coagulation function.

The activated clotting time (ACT) is routinely used to monitor heparin during cardiopulmonary bypass surgery. Activated clotting times may be influenced by a number of factors other than heparin. The presence of heparin in blood samples disguises the occurrence of non-heparin-related changes in coagulation function. During cardiopulmonary bypass, it is difficult to ascertain baseline clotting time fluctuations with ACT alone. Previous attempts to establish accurate baseline data were imprecise and involved extensive sample handling. In this study, we present data obtained using a modified (ACT) assay that incorporates heparinase. The heparinase test cartridge (HTC) instantaneously, specifically, and completely removes heparin in the blood sample at the initiation of the test. In conjunction with standard ACT techniques, the clinician is provided with heparin-independent (baseline) and functional clotting data. The HTC/ACT assay was used in a case study involving 19 patients undergoing cardiopulmonary bypass surgery. The data gathered indicate the usefulness of this assay in monitoring incidents of baseline drift, hemodilution, and hypercoagulation and the efficacy of protamine reversal.     

Effects of hypothermia on thrombelastography in patients undergoing cardiopulmonary bypass

Thrombelastography (TEG) correlates with postoperative chest drain output in patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with heparinase allows TEG monitoring during CPB, despite heparin anticoagulation. Hypothermia impairs coagulation, but these effects cannot be assessed by standard coagulation tests performed at 37 degrees C. The aim of this study was to assess the effects of hypothermia on TEG. Therefore, we have compared normothermic and temperature-adapted TEG in 30 patients undergoing CPB. Our data showed significantly impaired reaction time (r), kinetic time (k), and angle alpha (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude (MA), reflecting absolute clot strength, was not affected at temperatures of 33-37 degrees C. These findings indicate a decrease in the speed of clot formation, but not absolute deterioration in clot quality. Furthermore, heparinase-modified TEG indicated that there were nine cases in which heparin effects persisted after heparin reversal with protamine, providing a rational guide to protamine therapy.      

A case with no administration of protamine to neutralize heparin in aortic valve replacement with cardiopulmonary bypass

Systemic heparinization is necessary before cardiopulmonary bypass (CPB) in cardiac surgery, and protamine administration to neutralize heparin for hemostasis is required at the end of CPB. Because protamine is an allogeneic protein extracted from the sperm of specific fish, serious adverse reactions can occur during clinical application, with potentially catastrophic outcomes. A male patient received aortic valve replacement with CPB. Severe allergic reactions occurred postoperatively after protamine administration for neutralization. Emergency heparinization and CPB re-establishment were conducted with no further hemostatic treatment with protamine. However, the patient suffered a massive hemorrhage and was treated symptomatically with blood transfusion and rehydration. Following two thoracotomies for hemostasis, the patient healed and was eventually discharged. Protamine is irreplaceable as the only hemostatic that neutralizes heparin for cardiac CPB at present. However, because it is an alloprotein, it can cause serious allergic reactions after entering the human body, and caution should be exercised during the process of its clinical application.     

Heparin monitoring during cardiopulmonary bypass in congenital heart surgery

The Hepcon/HMS system automatically provides the activated clotting time and a whole blood heparin concentration. It also provides the adequate protamine dose by titration of protamine to heparin. 45 patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were studied by the Hepcon/HMS device. We measured the heparin dose response before heparin administration, and the ration between the dose of protamine (ml) which was necessary for heparin neutralization at the termination of CPB and the dose of total heparin (ml) in each patient. The value of heparin dose response ranged 120-390 (mean 228) IU/kg. The ratio between protamine dose and heparin dose varied 0.11-0.99 (mean 0.55). There was a statistically significant correlation between the duration of CPB and this ratio (r = -0.51, n = 45, p = 0.0005). From the standpoint of variances in the value of heparin dose response, conventional way of the heparin administration according to the patient's body weight alone may cause inadequacy of anticoagulation during CPB. A dose of protamine determined by Hepcon device that is smaller than a conventional dose of protamine prevents inadvertent overdose and, therefore, can reduce the adverse effects excessive protamine has.     

Heart failure due to rapid right ventricular volume overload in patients with pulmonary hypertension

We have described three cases of pulmonary artery hypertension (PAH). Two of them developed severe systemic hypotension and cardiac arrest following cardiopulmonary bypass (CPB). Imminent pre-operative right ventricular (RV) failure and subsequent myocardial injury during CPB may have contributed to the insult following CPB. In these cases, RV failure is presumably due to rapid volume overloading, since left atrial pressure (LAP) was essentially unchanged while right atrial pressure (RAP) was markedly elevated during the period of severe hypotension. Furthermore, these events may be attributed to protamine, since the circulatory derangement coincides with its administration. Thus, in these patients with severe PAH, blood transfusion should be carefully titrated under the strict evaluation of both LAP and RAP. Additionally, protamine should be infused at a rate slow enough to avoid concomitant hemodynamic changes. We have also reported a case of over-systemic PAH who was successfully managed intraoperatively by careful monitoring and discreet administration of protamine.     

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin-coated Equipment

Abstract: The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 ± 632 ng/ml) and C4a (1088 ± 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 ± 1045 ng/ml and 1494 ± 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 ± 177 μg/L) and 10 min after the administration of protamine (676 ± 314 μg/L) were significantly (p < 0.05) lower than in the other 2 groups (820 ± 341 and 893 ± 303 μg/L and 1365 ± 595 and 1,258 ± 622 μg/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma β-throm-boglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.