[Prevention of thromboembolism in trauma surgery by dose adjustment of low molecular weight heparin depending on levels of TAT and D-dimer]. / Prävention thromboembolischer Komplikationen in der Unfallchirurgie durch Dosisanpassung von niedermolekularem Heparin anhand TAT- und D-Dimer-Werten.

Deep vein thrombosis (DVT) is reported in up to 40% of trauma patients. The individual risk is nearly unpredictable. A daily single dose of a low molecular weight heparin (LMWH) was administered as prophylaxis to 518 trauma patients who were examined preoperatively and up to 10 days postoperatively in a prospective study. They were divided into two groups: group I comprised surgery of the hip and femur as well as total knee replacement and group II knee and lower leg surgery. Thrombin-antithrombin complex and D-dimer were analyzed. A second daily dose of LMWH was added if D-dimer exceeded the cutoff. If ultrasound was suspicious for DVT venography was added. Deep vein thrombosis was seen in five cases (group I=4, group II=1), without pulmonary embolism. TAT and D-dimer were significantly higher in group I than in group II ( p<0.005). One hundred patients, 79 of them belonging to group I, were treated with a second dose of LMWH. The daily cutoff had the highest sensitivity and specificity for day 4. Due to individual monitoring of coagulation markers, the risk for thromboembolism compared to actual data in the literature seems to be reduced.

Postoperative reduction of fibrinolysis as a prognostic factor of fatal outcome.

For the resection of an esophagus carcinoma a mortality rate of 2 to 30% was described. It is still unclear whether an abdominothoracic or transhiatal intervention is superior regarding the outcome. To investigate the prognostic value of fibrinolytic markers, plasmin-alpha2-antiplasmin (PAP) and D-dimer (DD) values were determined daily in the early postoperative period for 11 days. In addition, the course of PAP and DD concentrations was compared with the method of esophagectomy. Of the 28 patients enclosed in the study, 5 died between day 10 and day 34 owing to adult respiratory distress syndrome and septicemia. The PAP and DD concentrations increased in survivors after surgery until day 5 and day 7, respectively. The concentrations were twofold and 10-fold higher than the upper reference level. In contrast, four of five nonsurvivors showed an inadequate increase in PAP concentrations within the reference range, whereas the course of DD was inconspicuous. The sensitivity and specificity of PAP and DD in respect to a fatal outcome was calculated by receiver operating characteristic analysis based on all results: sensitivity 76% (PAP-cut off value 760 microg/L) and 49% (DD 6 mg/L), specificity 77% and 72%, respectively. The biochemical markers showed no significant differences between the abdominothoracic and transhiatal esophagectomy. In the abdominothoracic intervention, lower PAP and higher DD concentrations were observed. The results showed that the PAP concentrations could detect a fatal outcome within the first 5 days after surgery.

Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.

BACKGROUND: The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results-In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level. CONCLUSIONS: These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.

Comparison of diagnostic performance of cardiac troponin I on the IMMULITE system with other automated troponin I assays in minor myocardial damage.

An analytical and clinical evaluation of cardiac troponin I (cTnI) on the IMMULITE system is presented. The assay results were compared with those of the Stratus II and the Dimension RxL-HM. A between-run imprecision CV < 20% was found at a cTnI concentration of 0.23 microg/L (functional limit of detection). On the basis of a reference study including 215 patients without ischemic heart disease (97.5th percentile: 0.294 microg/L) and 36 patients clinically classified as having stable angina pectoris (<0.22 microg/L) a preliminary cutoff level of 0.3 microg/L was defined. Assay linearity, sample stability, influence of sample material and method comparison studies were performed. In patients with Duchenne's disease, chronic hemodialysis treatment, pulmonary embolism, coronary artery bypass surgery and minimally cardiac surgery the cTnI results of the IMMULITE agreed better with the Dimension RxL-HM than with the Stratus II data. Of 142 samples from patients with unstable angina 67 samples were classified as cTnI positive with the IMMULITE, 76 with the Dimension RxL-HM, and 62 with the Stratus II. In conclusion, the new assay is sensitive for the determination of cTnI and easy to perform within 45 min.

Analytical and clinical evaluation of troponin I determination on dimension RXL-HM.

The evaluation of cardiac troponin I (cTnI) on the Dimension RxL-HM analyzer is presented. The one-step enzyme immunoassay is based on two cTnI specific monoclonal antibodies. Performed on a separate module of the analyzer, assay-time is 17 minutes. Using as criterion a between-run impression CV <20% the functional limit of detection was set at 0.1 microg/l. Cutoff level for minor myocardial damage of 0.1 microg/l was found. In Duchenne's dystrophy, patients showed increased cardiac Troponin T (cTnT) but no increased cTnI. In patients with a history of coronary heart disease undergoing chronic hemodialysis, cTnT and cTnI were increased. In different patients with submassive pulmonary embolism, increased cTnI was determined. In coronary artery bypass surgery without perioperative myocardial infarction, patients with extracorporeal circulation showed significantly higher cTnI at 24 h after surgery than those with minimal cardiac surgery. In patients with unstable angina, increased cTnI was found more often than on Stratus analyzer. In conclusion, the new assay is a very sensitive cTnI assay, fast and easy to perform in parallel to enzyme and substrate assays.

Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D-Dimer.

In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer. Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2 mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a day. Color Doppler ultrasound was performed between the fifth and seventh p.o. days. Patients were divided into a high-risk (group 1: hip, femur, or knee replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D-Dimer levels than group 2 (p<0.001). Measurement of D-Dimer on days 2 and 4 p.o. showed a sensitivity of 100% and a specificity of 72.8% in identifying patients at risk (i.e., D-Dimer>2 mg/L after day 4 p.o.). The overall deep vein thrombosis (DVT) rate in group 1 was 3.9%, and the rate of proximal DVT was 1.96%. In group 2, one distal DVT (0.8%) occurred. The results show that D-Dimer is a useful marker to monitor p.o. coagulation activation and to manage LMWH prophylaxis in trauma surgery patients.

Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension.

Hypertension is a side effect of systemically administered glucocorticoids, but the underlying molecular mechanism remains poorly understood. Ingestion of dexamethasone by rats telemetrically instrumented increased blood pressure progressively over 7 days. Plasma concentrations of Na(+) and K(+) and urinary Na(+) and K(+) excretion remained constant, excluding a mineralocorticoid-mediated mechanism. Plasma NO(2)(-)/NO(3)(-) (the oxidation products of NO) decreased to 40%, and the expression of endothelial NO synthase (NOS III) was found down-regulated in the aorta and several other tissues of glucocorticoid-treated rats. The vasodilator response of resistance arterioles was tested by intravital microscopy in the mouse dorsal skinfold chamber model. Dexamethasone treatment significantly attenuated the relaxation to the endothelium-dependent vasodilator acetylcholine, but not to the endothelium-independent vasodilator S-nitroso-N-acetyl-D,L-penicillamine. Incubation of human umbilical vein endothelial cells, EA.hy 926 cells, or bovine aortic endothelial cells with several glucocorticoids reduced NOS III mRNA and protein expression to 60-70% of control, an effect that was prevented by the glucocorticoid receptor antagonist mifepristone. Glucocorticoids decreased NOS III mRNA stability and reduced the activity of the human NOS III promoter (3.5 kilobases) to approximately 70% by decreasing the binding activity of the essential transcription factor GATA. The expressional down-regulation of endothelial NOS III may contribute to the hypertension caused by glucocorticoids.

Reference values for a homogeneous Ferritin assay and traceability to the 3rd International Recombinant Standard for Ferritin (NIBSC code 94/572).

Reference values for two ferritin assays (Tina-quanta Ferritin, Enzymun, both Roche Diagnostics, Mannheim, Germany) were established (136 males and 139 females). To rule out inflammation as well as iron deficiency in the reference population, subjects with the C-reactive protein concentration < 5 mg/l, and zinc protoporphyrin < 40 micromol/mol heme and the soluble transferrin receptor < 3 mg/l were selected. Taking into account latent iron deficiency as well as hereditary hemochromatosis the 5-95 percentile range was as follows: male, 27-365 microg/l; female, 13-148 microg/l for Tina-quanta and 12-151 microg/l for Enzymun. The Tina-quanta Ferritin assay showed a very good correlation (r > or = 0.990) to Enzymun ferritin, Ferritin Abbott (Abbott Diagnostics, Delkenheim, Germany), N Latex Ferritin (Dade Behring, Marburg, Germany) and the Ferritin Chiron (Chiron Diagnostics, Fernwald, Germany). However, the slopes of the standard principal component method analysis were calculated to be between 1.03 (Enzymun) and 1.41 (N Latex Ferritin). For four assays the median recovery of the 3rd International Recombinant Ferritin Standard (NIBSC 94/572) measured by serial dilution was 89-109%. The N Latex Ferritin assay recovered half of the target values. Because of the good correlation with other assays, a matrix effect is likely. The question arises whether the manufacturers' agreement on the recombinant ferritin standard would harmonize ferritin measurement.

Retinal vascular occlusion and deficiencies in the protein C pathway.

PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also screened 209 consecutive inpatients with deep vein thrombosis from the same geographic region for resistance to activated protein C as well as protein C and protein S deficiencies. RESULTS: Ten (29%) of 35 patients with central retinal vein occlusion (CRVO) had factor V R506Q mutation. The factor V R506Q mutation was detected in four (19%) of 21 patients with branch retinal vein occlusion. The higher frequency in factor V R506Q mutation compared with the expected 9% mutation prevalence in a white population was highly significant for the central retinal vein occlusion group but not for the branch retinal vein occlusion group. In all patients with resistance to activated protein C, the factor V R506Q mutation was detected; 16 were heterozygous, one homozygous. No cases of lupus anticoagulants, protein C, or protein S deficiencies were detected. Forty (19%) of 209 patients with deep vein thrombosis were carriers of the factor V R506Q mutation. CONCLUSIONS: The prevalence of the factor V R506Q mutation is similar in patients with central retinal vein occlusion and patients with deep vein thrombosis and represents a relevant risk factor. Screening for this mutation is therefore recommended in all patients with central retinal vein occlusion.

[Hereditary disorders of the protein C system in central artery and branch arteriolar occlusions]. / Hereditäre Störungen des Protein-C-Systems bei Zentralarterien- und Arteriolenastverschlüssen.

BACKGROUND: Resistance to activated protein C (APC) is the most common hereditary defect in patients with venous thrombosis. There are conflicting reports on the prevalence of APC resistance in patients with arterial thrombosis, e.g. coronary arteries, compared to the APC resistance prevalence among the normal population. The prevalence of APC resistance in branch retinal artery occlusion (BRAO) and central retinal artery occlusion (CRAO) is unknown. PATIENTS AND METHODS: 29 consecutive patients with arterial retinal occlusions (BRAO, n = 12; CRAO, n = 17) were included in this prospective study over a 23-months-period. We searched for APC resistance, protein C or S deficiencies, as well as for acquired vascular risk factors. Factor-V-deficient plasma and genetic analysis with a PCR method were employed for APC resistance determination. Protein C and protein S activity were determined with functional tests. RESULTS: APC resistance was found in 3 of 29 patients (10.3%). Two of these patients had BRAO and one patient CRAO. Comparing this prevalence to the APC resistance prevalence within the normal population (9%), the difference was not statistically significant. 27 patients (93.1%) had one or more vascular risk factors (arterial hypertension = 19 [65.5%], hyperlipidaemia = 14 [48.2%], smoking = 7 [24.1%], diabetes mellitus = 5 [17.2%], carotid artery stenosis = 5 [17.2%]). CONCLUSIONS: We could not find an increased prevalence of APC resistance in patients with CRAO or BRAO when compared to the normal population.

Collagen type I metabolism after bone surgery.

This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 microg/l, second week 337 microg/l; P < 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: < 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity.

Genetic thrombophilia in patients with retinal vascular occlusion.

BACKGROUND: This study was carried out to determine the prevalence of genetic thrombophilia in patients with retinal vascular occlusion. METHODS: We investigated 116 consecutive patients with central retinal vein occlusion (CRVO, n = 48), branch retinal vein occlusion (BRVO, n = 33), central retinal artery occlusion (CRAO, n = 21), branch retinal artery occlusion (BRAO, n = 14). All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, prothrombin gene mutation (G20210A), resistance to activated protein C (APCR), and were screened for vascular disease risk factors. APC resistance was confirmed by a PCR method to detect the factor V R506Q mutation. A PCR method was also used to detect the G20210A mutation. For comparative purposes, we screened 209 consecutive patients with deep vein thrombosis (DVT) and 581 patients with coronary heart disease (control group) for APC resistance. RESULTS: 13 (27%) of 48 patients with CRVO had the factor V R506Q mutation. The factor V R506Q mutation was detected in six (18%) of 33 patients with BRVO, but in only one patient with CRAO and in two patients with BRAO. Other thrombophilic defects were not detected. The APCR prevalence within the CRVO group was significantly increased when compared to the control group (8%). There was no significant difference in the factor V R506Q mutation prevalence between the CRVO group and the DVT group (19%). CONCLUSION: The factor V R506Q mutation is the most common cause of genetic thrombophilia in patients with CRVO and has a similar prevalence as in DVT patients.

[Value of molecular markers for administration of anticoagulant therapy after heart valve replacement]. / Stellenwert der molekularen Marker in der Einstellung der Antikoagulantientherapie nach Herzklappenersatz.

In a prospective study, 39 patients following aortic or mitral valve replacement underwent investigation of molecular markers (prothrombin fragment F1+2, Factor II) in the initial phase of oral anticoagulation therapy (OAT). The results demonstrate that, despite INR being in the depicted range, the levels of the molecular markers remained high, indicating an increased risk of thromboembolic events. This leads to the conclusion that molecular markers are superior to INR in the monitoring of the early phase of OAT.

[Follow-up of collagen and bone metabolism in patients with cement-free total hip endoprosthesis]. / Verlaufsbeobachtung des Kollagen- und Knochenstoffwechsels bei Patienten mit zementfreier Hüfttotalendoprothese.

INTRODUCTION: This study investigated the influence of concentration and activity of several markers of the collagen and bone metabolism and their impact on ingrowth of non-cemented total hip arthroplasty. METHODS: 40 patients underwent an implantation of a ABG-prosthesis. Before surgery and 1, 2, 12 and 24 weeks after it serum concentrations of PICP, ICTP, IGF-1, ON, b-AP, Calcium, Phosphate, GPT and Creatinin were measured and a collagen ratio (CQ) was calculated. RESULTS: PICP decreased until 1st week, increased at 2nd week and decreased again after that time. ICTP increased significantly in 1st week, reached a maximum in 2nd week and decreased after that. b-AP decreased in 1st week but increased after that time. IGF-1 and ON decreased significantly after surgery but increased later. Calcium and Phosphate always showed normal values. CQ decreased in 1st week in males (45%) and females (60%), but increased later on. CONCLUSION: These markers investigated made it possible to estimate the osteointegration of non-cemented total hip arthroplasty and confirm radiologic and histomorphometric results of the literature.

Long-term metabolic effects in patients with urinary diversion.

The use of intestinal segments in genitourinary reconstruction could influence vitamin metabolism and affect the skeletal bone and its mineral content in the long term. In 137 patients, serum levels of the vitamins A, B1, B2, B6, B12, D, and E and of folic acid, bile acid, and ammonia as well as levels of intracorpuscular vitamin B12 and folic acid were examined and a red blood cell count was performed. The patients were divided into three groups (< or = 2 years, > 2 to < or = 4 years, and > 4 years after surgery) as well as into children and adults. In addition, bone mineral density (dual-photon absorptiometry) was measured in 25 patients. Of these, 16 patients were approximately 16.8 years s/p rectal reservoir, 6 were approximately 20.5 years s/p colonic conduit, two were 6 and 8 years s/p ileocecal pouch, and one adolescent was 5 years s/p ileal bladder augmentation. In all patients the levels of vitamins A, B1, B2, B6, D, and E and of folic acid, bile acid, and ammonia as well as the red blood cell count were within normal ranges. In children (n = 51) there was no significant drop in vitamin B12 levels after the operation. In adults (n = 86), serum vitamin B12 levels dropped significantly from 402 +/- 182 ng/l during the first 2 years after the operation to 292 +/- 204 ng/l after the 4th year (normal range 240-1,100 ng/l). No significant increase in the intracorpuscular vitamin B12 level was observed during the same period. The bone mineral density was normal in all 25 patients with different types of urinary diversion. In addition to regular examination (sonography, creatinine levels, and base excess), vitamin B12 levels should be determined at 4 years after urinary diversion. It remains unclear whether substitution is necessary. However, substitution is easy to achieve and cheaper than the regular determination of vitamin B12. No decrease in bone mineral content was seen in the long-term follow-up with early correction of the base excess (below -2.5).

Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults.

OBJECTIVE: Adults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD. DESIGN: At the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the 'GH group') or placebo (the 'placebo group'). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months. PATIENTS: Of the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 +/- 10.1 years. All patients had been GH-deficient for at least 2 years before the start of the study. MEASUREMENTS: Rates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross-linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the non-dominant forearm by single-photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU). RESULTS: The main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months. CONCLUSIONS: Our results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long-term GH therapy.

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

High-dose epsilon-aminocaproic acid versus aprotinin: antifibrinolytic efficacy in first-time coronary operations.

BACKGROUND: The antifibrinolytic efficacy of a high-dose regimen of epsilon-aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time coronary operations. METHODS: In a prospective, double-blinded, randomized study, 20 patients received high-dose epsilon-ACA (10 g both as a loading and cardiopulmonary bypass priming dose, 2.5 g/h until 4 hours after protamine), and another 20 patients received aprotinin (2 x 10(6) KIU [280 mg] for loading and priming, 0.5 x 10(6) KIU/h [70 mg/h]). Ten untreated patients served as controls. RESULTS: Both agents reduced postoperative levels of thrombin/antithrombin III complexes, D-dimers, fibrin degradation products, free plasma hemoglobin (epsilon-ACA versus aprotinin, p = not significant; p < 0.05 versus controls), and amount of retransfused autologous blood (p < 0.001). Epsilon-ACA increased, aprotinin suppressed antiplasmin-plasmin complex generation (epsilon-ACA versus controls, p < 0.02; epsilon-ACA versus AP, p < 0.0001). For 4 hours after discontinuation, more chest drainage occurred with epsilon-ACA than aprotinin (137 +/- 90 mL versus 62 +/- 29 mL; means +/- standard deviation; p < 0.02). Cumulative 12-hour drainage was similar for aprotinin (391 +/- 220 mL) and epsilon-ACA (582 +/- 274 mL), but higher without inhibitor (1,091 +/- 541 mL; p < 0.001 versus drugs). Postoperatively, aprotinin was associated with the lowest autologous retransfusion incidence and highest hematocrits (p < 0.01 versus epsilon-ACA). Homologous transfusion exposures did not differ. CONCLUSIONS: In first-time coronary operations, higher postoperative hematocrit and less shed blood retransfusion constitute only subtle advantages of aprotinin over high-dose epsilon-ACA.