Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation.

Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.

Circulating tissue factor and microparticles are not increased in patients with deep vein thrombosis.

BACKGROUND: Circulating tissue factor (TF) is associated with inflammation and may contribute to thrombotic events. Aim of this study was to analyze circulating TF activity and proinflammatory cytokines in patients with deep venous thrombosis. PATIENTS AND METHODS: Forty-eight patients with deep vein thrombosis and 45 control subjects were included. Venous blood samples were obtained at diagnosis for analysis of TF activity, TF antigen, prothrombin fragment F1 + 2, microparticles (expressing phosphatidylserine and supporting FXa generation), Interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 and tumor-necrosis-factor-alpha (TNF). RESULTS: TF antigen, activity and microparticles were similar in both groups: In contrast, a significant increase in plasma IL-6, IL-8 and F1 + 2 levels was found in thrombosis. This increase in IL-6 and IL-8 as well as F1 + 2 was not correlated with the extent of thrombosis, predisposing factors or onset of symptoms. CONCLUSIONS: Circulating TF and microparticles are not elevated in deep venous thrombosis. The increase in IL-6, IL-8 and F1 + 2 during thrombosis was not proportional to the extent or predisposing risk factors.

The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

PURPOSE: Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. METHODS: The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. RESULTS: Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. CONCLUSION: We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and ross operation.

BACKGROUND: Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. METHODS AND RESULTS: A total of 21 children with transposition of the great arteries at a mean interval of 11.2+/-2.9 years after ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.

Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass.

OBJECTIVE: The occurrence of a systemic inflammatory reaction during cardiac surgery with cardiopulmonary bypass (CPB) has been well established, and the heart itself has been shown to release inflammatory mediators after ischemia. The hypothesis of the present study was that the lungs are also a site of inflammatory responses during early reperfusion. METHODS: In 20 consecutive patients undergoing coronary artery bypass grafting, blood was simultaneously drawn from the right atrium (RA) and the pulmonary vein (PV) before CPB and at 1 min, 10 min, and 20 min of reperfusion. The levels of interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha were determined, as well as the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes. As a measure of the pulmonary release, ratios of PV and RA levels were calculated. RESULTS: Before CPB, the concentrations of cytokines tended to be lower in the PV compared with the RA. At 1 min of reperfusion, no significant concentration increases were found in the PV. At 10 min of reperfusion, the PV/RA ratio (mean +/- SEM) for IL-6 was 2.06 +/- 0.37 and 1.24 +/- 0.15 for IL-8 (p = 0.02 and p = 0.04, respectively, compared with the pre-CPB ratios of 0.89 +/- 0.4 and 0.99 +/- 0.2). At 20 min of reperfusion, PV/RA ratios for IL-6 (1.95 +/- 0.37) and IL-10 (0.99 +/- 0.4) were higher than before CPB (0.89 +/- 0.04, p = 0.05 and 0.85 +/- 0.06, p = 0.03, respectively). Adhesion molecule counts on platelets and polymorphonuclear neutrophils (PMNs) tended to be higher in the PV than in the RA before CPB. At 1 min of reperfusion, the PV/RA ratio of CD41 on monocytes (0.89 +/- 0.04) and of CD41 on PMNs (1.05 +/- 0.05) was less than before CPB (1.24 +/- 0.08, p = 0.0002 and 1.55 +/- 0.14, p = 0.0002). At 10 min and 20 min of reperfusion, similar changes were found. CONCLUSIONS: The observed changes indicate an inflammatory response of the lungs. Proinflammatory cytokines are increased in pulmonary venous blood. At the same time, activated blood cells are retained in the pulmonary circulation. This may contribute to pulmonary dysfunction almost routinely observed after CPB.

Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?

OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS: A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

Sodium nitroprusside in patients with compromised left ventricular function undergoing coronary bypass: reduction of cardiac proinflammatory substances.

OBJECTIVE: The aim of the present study was to investigate whether the nitric oxide donor sodium nitroprusside can reduce the cardiac inflammatory response during coronary artery bypass grafting in patients with severely compromised left ventricular function. METHODS: Patients (n = 30) were assigned to receive placebo or sodium nitroprusside (0.5 microg. kg(-1). min(-1)) for the first 60 minutes of reperfusion. Interleukin 6, interleukin 8, and tumor necrosis factor alpha levels; platelet adhesion molecule CD41 and CD62 levels; and CD11b on leukocytes were determined in the radial artery and coronary sinus before cardiopulmonary bypass and during reperfusion (1, 5, 10, 35, and 75 minutes). RESULTS: At 1 minute of reperfusion, coronary venous levels of CD41-positive polymorphonuclear leukocytes were 8% lower than arterial levels in the placebo group and 18% higher in the sodium nitroprusside group (P =.021). At 5 minutes of reperfusion, the respective levels were 29% and 1% for interleukin 6 (P =.015), -5% and 20% for CD41-positive monocytes (P =.032), and -2% and 16% for CD11b-positive monocytes (P =.038). At 10 minutes of reperfusion, these levels were -14% and 21% for CD41-positive monocytes (P =.006). At 35 minutes of reperfusion, these levels were -13% and 7% for CD41-positive monocytes (P =.017), -41% and 23% for CD11b-positive monocytes (P =.001), and 7% and 25% for CD62-positive platelets (P =. 041). At 75 minutes of reperfusion, the levels were 15% and -7% for tumor necrosis factor alpha (P =.025) and -10% and 10% for CD62-positive platelets (P =.041). CONCLUSIONS: Transcardiac production of proinflammatory cytokines is reduced in patients undergoing coronary artery bypass grafting treated with the nitric oxide donor sodium nitroprusside. At the same time, less activated leukocytes and platelets are retained in the coronary circulation.

Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass causes inflammatory reactions leading to organ dysfunction postoperatively. This study was undertaken to determine whether using patients' own lungs as oxygenator in a bilateral circuit (Drew-Anderson Technique) could reduce systemic inflammatory response to cardiopulmonary bypass, improving patients clinical outcome following coronary artery bypass grafting. METHODS: A prospective randomized controlled trial involving 30 patients, divided in two groups of 15 patients each, undergoing elective coronary artery bypass grafting, was undertaken. In the Drew-group bilateral extracorporeal circulation using patient's lung as oxygenator was performed. The other patients served as control group, where standard cardiopulmonary bypass procedure was used. RESULTS: Pro-inflammatory and anti-inflammatory mediators were measured. Peak concentrations of proinflammatory interleukin-6, interleukin-8, were significantly lower in 15 patients undergoing Drew-Anderson Technique compared with the concentrations measured in 15 patients treated with standard cardiopulmonary bypass technique. Differences in patient recovery were analyzed with respect to time of intubation, blood loss, intrapulmonary shunting, oxygenation, and respiratory index. In patients undergoing uncomplicated coronary artery bypass grafting procedures bilateral extracorporeal circulation using the patients' own lung as oxygenator provided significant biochemical and clinical benefit in comparison to the standard cardiopulmonary bypass procedure. CONCLUSIONS: This prospective randomized clinical study has demonstrated that exclusion of an artificial oxygenator from cardiopulmonary bypass circuit significantly decreases the activation of inflammatory reaction, and that interventions that attenuate this response may result in more favorable clinical outcome.

Influence of high- and low-dose aprotinin on activation of hemostasis in open heart operations.

BACKGROUND: The protease inhibitor aprotinin reduces hemostatic activation and blood loss after cardiac operations. The aim of the present study was to investigate the influence of two different aprotinin doses on hemostatic activation and to identify the most effective dose to reduce the postoperative bleeding tendency. METHODS: In a prospective, randomized, double-blind clinical trial, 230 patients scheduled for routine open heart operations received either high-dose (group H) or low-dose (group L) aprotinin. Primary outcome measures were the level of F(1+2) prothrombin fragments as a marker of thrombin generation, the level of D-dimers as an indicator of fibrinolysis, and the amount of postoperative blood loss. Allogeneic blood transfusion was recorded as a secondary outcome measure. RESULTS: Aprotinin plasma concentrations 5 minutes after the onset of cardiopulmonary bypass were 166 +/- 45 kallikrein inactivator units per milliliter in group H and 118 +/- 30 kallikrein inactivator units per milliliter in group L (p < 0.05). Fibrinolytic activation was reduced significantly in group H compared with group L: the level of D-dimers at the end of CPB was 1,027 +/- 781 ng/mL and 1,977 +/- 1,001 ng/mL, respectively, in the two groups (p < 0.05). However, thrombin generation (F(1+2) fragments) did not differ between the two groups (7.4 +/- 3.5 nmol/L in group H and 8.6 +/- 4.3 nmol/L in group L). Twenty-four-hour postoperative blood loss was 663 +/- 461 mL in group H compared with 877 +/- 513 mL in group L (p < 0.05), and the corresponding allogeneic blood requirement was 1.3 +/- 1.9 U in group H and 1.9 +/- 2.3 U in group L (p < 0.05). CONCLUSIONS: A high-dose aprotinin regimen was significantly more effective than a low-dose regimen in attenuating fibrinolysis and reducing the bleeding tendency and allogeneic blood requirements, but not in reducing F(1+2) prothrombin fragments. High-dose aprotinin therapy appears to be superior to low-dose therapy.

Cluster-oriented discriminant analysis; taxonomic classification of the thyroid function.

A computer assisted procedure for the diagnosis of thyroid diseases, based on seven clinical chemical parameters, is proposed. The population studied consisted of 592 consecutive outpatients with a tentative diagnosis of thyroid disease. Thyroxine, triiodothyronine, T3 uptake test, TSH before and after TRH application, its difference and thyroxine binding globulin have been determined. The patients were clinically examined and in each case a Tc-scintigram was obtained. As a first step, 20 biochemical patterns were defined by cluster analysis (pattern cognition). T check how good in grouping process was, linear discriminant analysis was applied after which the reclassification rates were very satisfactory. The clusters found corresponded well to the pathophysiological situations with some exceptions. As a second step, patients were assigned to these patterns by use of the derived discriminant functions (pattern recognition). The proposed method seems to have some advantages over other diagnostic models published hitherto.

Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol.

Genetic heterogeneity has been suggested in xanthinuria from the hitherto unexplained ability of some patients with this hereditary disorder to convert allopurinol to its active metabolite oxipurinol--an activity generally attributed to xanthine oxidase. This study provides evidence that the enzyme aldehyde oxidase is also deficient in xanthinuric patients not converting allopurinol to oxipurinol, whereas a xanthinuric patient with normal formation of oxipurinol had normal aldehyde oxidase activity. It is concluded that the enzyme aldehyde oxidase is the principal enzyme responsible for the formation of oxipurinol in man.

Significant leukocyte and platelet retention during pulmonary passage after declamping of the aorta in CABG patients.

During reperfusion of the heart and the lungs in patients undergoing coronary artery bypass grafting, these organs have been shown to release inflammatory mediators. The present study was performed to quantitatively determine cellular retention or washout during pulmonary passage in early reperfusion. In 14 consecutive patients undergoing coronary artery bypass grafting blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The counts for platelets, leukocytes and the leukocyte subsets polymorphonuclear neutrophils (PMN), lymphocytes and monocytes were determined. Pulmonary veno-right atrial (transpulmonary) differences are given in percent with respective right atrial values being considered as 100%. Before CPB leukocyte counts were 4.7 +/- 0.5 in right atrium and 4.2 +/- 0.4 in pulmonary vein, x10(9)/l, resp. (transpulmonary difference of -8 +/- 3%). During reperfusion, pulmonary retention was in the range of 20-23% (p <0.01 vs. right atrial value). The basal values for PMN were 2.4 +/- 0.3 in right atrium and 1.9 +/- 0.3 in pulmonary vein, x10(9)/l, resp. (transpulmonary difference -15 +/- 8%). Thereafter, retention was in the range of 25-30% (p <0.01 vs. right atrium). Basal values for lymphocytes were 1.5 +/- 0.2 in right atrium and 1.6+/-0.3 in pulmonary vein, x10(9)/l, resp. (transpulmonary difference +6 +/- 10%). A tendency towards a washout of lymphocytes at 1 min reperfusion (+1 +/- 12%) was followed by retention of these cells at 10 and 20 min reperfusion (-14 +/- 12% and -10 +/- 5%, p <0.05 vs right atrium). Before ischemia monocyte counts were 0.7 +/- 0.2 in right atrium and 0.6 +/- 0.2 in pulmonary vein, x10(9)/l, resp. (transpulmonary difference -10 +/- 4%) and -9 +/- 9%, -27 +/- 12% (p <0.05 vs right atrium) and -22 +/- 14% at 1, 10 and 20 min reperfusion. During early reperfusion of the lungs after declamping of the aorta, significant amounts of leukocytes, platelets and the leukocyte subsets are retained in the pulmonary vascular bed. These retained cells may be responsible for the previously described pulmonary release of cytokines.

Equivalence reliability of the functional independence measure for children (WeeFIM) administration methods.

OBJECTIVE: This study examined the equivalence reliability of two administration methods for the Functional Independence Measure for Children (WeeFIM). The two methods were direct observation of child performance and parental interview. METHOD: Thirty children between the ages of 19 months and 71 months with identified developmental disabilities were included in this study. The direct observation and interview methods were administered in random order to each subject within a 3-week period. The direct observation was completed in the educational setting, and the WeeFIM interview was obtained by either in-person interview or telephone interview with the parent. RESULTS: The intraclass correlation coefficient (ICC) for total WeeFIM ratings was .93, indicating consistency between the two administration methods. Analysis of the WeeFIM Motor (13 items) and Cognitive (5 items) domains yielded ICC values of .93 and .75, respectively, suggesting greater consistency for items measuring motor-related skills. CONCLUSION: The results demonstrate good agreement for total ratings when the WeeFIM is administered by direct observation and by interview with a parent. The findings establish the clinical usefulness of information collected by clinical interview.

[Observations on the cost effectiveness of various methods of electrolyte determination]. / Betrachtungen zur ökonomischen Effizienz von verschiedenen Methoden zur Elektrolytbestimmung.

New analytical methods have to be considered also with respect to their economic efficiency. Here we present the application of an economic analysis based on the rules of applied economics in our institute for clinical chemistry and laboratory medicine. We started with an analysis of laboratory structure and economic efficiency in 1988, which since then has been followed by a continuously performed laboratory controlling system. The results of unit costing show the different cost groups, which add up to the cost of a single electrolyte determination. Regarding the transferability of our data to other laboratories, one has to consider that the main cost groups besides personnel cost are the apportionment of the overhead cost and the depreciation cost; both may vary markedly between each laboratory. Variable cost (reagents and consumables) differ widely from flame photometry to enzymatic electrolyte determination, but they amount only to 3-15% of the total cost.

High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery.

OBJECTIVE: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University-affiliated cardiac center. PARTICIPANTS: Twenty patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM. MEASUREMENTS AND MAIN RESULTS: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002). CONCLUSIONS: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin.

Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery. A double-blind, placebo-controlled study.

BACKGROUND: Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin. The current study was designed to test the efficacy of aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity. METHODS: In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded. RESULTS: Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05). CONCLUSIONS: Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of aprotinin, because the prolonged CACT in the aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of aprotinin.

Evaluation of a new valproic acid enzyme immunoassay and comparison with a capillary gas-chromatographic method.

A new homogeneous immunoassay (EMIT) for valproic acid was evaluated. Besides testing the manual version of this enzyme immunoassay, we also developed two mechanized procedures for centrifugal analyzers (the CentrifiChem and the COBAS system), which take less time and are more precise than the manual method. Within-assay precision (CV) was 4.5% with the manual technique and 2% with the analyzers. Between-assay precision (CV) ranged from 4 to 13% for all three techniques. Accuracy of th manual method was checked by dilution and analytical recovery experiments. Our comparison of the EMIT results with those obtained by a comparison method (capillary gas chromatography) showed no significant difference. No interference from hemolysis, hyperbilirubinemia, or aliphatic amino acids was observed. At high concentrations of bile acids and with lipemic sera the analytical recovery rates decreased slightly, to 87% and 92%, respectively.

Prevalence and risk factors of hepatitis C infection after cardiac surgery in childhood before and after blood donor screening.

BACKGROUND: Since 1974, the risk of acquiring non-A non-B hepatitis by blood transfusion is well known. In 1999, children having had polytransfusions (group 1) after cardiac surgery prior to the establishment of routine blood donor screening could be identified as a risk group for hepatitis C (HCV) infection. PATIENTS AND METHODS: In 1991, Germany began screening blood donors for hepatitis C. To describe the risk after the implementation of blood donor screening, we studied 211 children (group 2) having had open heart surgery after 1991 and compared prevalence for anti-HCV antibodies and known risk factors to group 1. RESULTS: None of the 211 patients with cardiac surgery after 1991 had detectable anti-HCV antibodies, compared to 67 of the 458 patients (14.6%) of group 1 (p < 0.001). The mean number of operations in both groups was virtually the same (mean 1.7 +/- 0.9 in group 1, mean 1.6 +/- 0.9 in group 2, p = 0.075), whereas the total number of blood products per patient differed significantly (group 1 mean 8 +/- 17.6, group 2 mean 3.5 +/- 2.8; p < 0.001). Multivariate analysis of risk factors demonstrates affiliation to group 1, transfusion of fresh blood, warm whole blood, heparinized blood (p < 0.001) and plasma (p = 0.004) as significant. CONCLUSION: After the implementation of blood donor screening, the risk for HCV infection after cardiac surgery in childhood dropped significantly from 14.6% to < 0.5%. These data show the necessity of HCV screening for patients at risk (operations before 1991) and do not favor a general screening for all patients.

Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures?

OBJECTIVE: To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment. DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Fifty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants. MEASUREMENTS AND MAIN RESULTS: After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024). CONCLUSION: The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters.

Realistic modeling of clinical laboratory operation by computer simulation.

An important objective of laboratory management is to adjust the laboratory's capability to the needs of patients' care as well as economy. The consequences of management may be changes in laboratory organization, equipment, or personnel planning. At present only one's individual experience can be used for making such decisions. We have investigated whether the techniques of operations research could be transferred to a clinical laboratory and whether an adequate simulation model of the laboratory could be realized. First we listed and documented the system design and the process flow for each single laboratory request. These input data were linked by the simulation model (programming language SIMSCRIPT II.5). The output data (turnaround times, utilization rates, and analysis of queue length) were validated by comparison with the current performance data obtained by tracking specimen flow. Congruence of the data was excellent (within +/- 4%). In planning experiments we could study the consequences of changes in order entry, staffing, and equipment on turnaround times, utilization, and queue lengths. We conclude that simulation can be a valuable tool for better management decisions.