Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism.

BACKGROUND: To investigate the frequency of cardiac troponin I (cTnI) increases in patients with pulmonary embolism (PE) and to assess the correlation between this finding, the clinical presentation, and outcomes. METHODS: Consecutive patients admitted to the coronary care unit with acute PE were prospectively enrolled between January 2000 and December 2001. cTnI was sequentially determined. Various cut off concentrations were analysed, but patients were categorised prospectively as having increased or no increased cTnI based on a cut off concentration of 0.6 ng/ml. The main outcome measure was in-hospital mortality. RESULTS: On admission, 14 of the 48 patients (29%) had cTnI concentrations greater than the receiver operating characteristic curve value used to diagnose acute myocardial infarction (> 0.6 ng/ml). Subsequently, six patients developed increases for an overall prevalence of 42% (20 of 42). The prevalence was higher when lower cut off concentrations were used: 73% (35 of 48) at the 99th centile and 60% (29 of 48) at the 10% coefficient of variability. Increased cTnI > 0.6 ng/ml was associated with a slower oxygen saturation (86 (7)% v 93 (4)%, p < 0.0001) and more frequent involvement of the main pulmonary arteries as assessed by spiral computed tomography (100% v 60%, p = 0.022). In-hospital mortality was 36% (5 of 14) of patients with increases > 0.6 ng/ml v 3% (1 of 42) of patients with lower concentrations (p = 0.008). Increased cTnI > 0.6 ng/ml on admission was the most powerful predictor of mortality (p = 0.046). CONCLUSIONS: In high risk patients with acute PE, cTnI was frequently detected on admission. It was the strongest independent predictor of mortality.

[Low-molecular weight heparin and acute coronary syndrome: theoretical background and its use in clinical practice]. / Eparine a basso peso molecolare e sindromi coronariche acute: razionale teorico ed uso nella pratica clinica.

Thrombosis is responsible for the acute manifestations of coronary artery disease. Intravenous heparin has been shown to be effective in reducing the risk of death or myocardial infarction in patients with acute coronary syndromes. Compared to standard heparin, low-molecular weight heparins (LMWHs) have improved pharmacological and pharmacokinetic properties. A number of LMWHs, such as nadroparin, dalteparin and enoxaparin, have been evaluated in patients with acute coronary syndromes. FRISC (Fragmin during Instability in Coronary Artery Disease) and FRIC (Fragmin in Unstable Coronary Artery Disease), evaluated dalteparin and found the LMWH to be more effective than aspirin alone (FRISC) and as effective as heparin in a direct comparison (FRIC). In a small trial, nadroparin was shown to significantly reduce the risk of ischemic outcomes compared with a combination of aspirin and heparin, but this effect was no longer significant in the large FRAX.I.S. trial (FRAXiparine in Ischaemic Syndrome). Enoxaparin resulted in a statistically significant reduction in the combined outcome of death, myocardial infarction and recurrent angina or of urgent revascularization when compared with heparin in the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events) and TIMI 11B trials. Meta-analyzing of the data of these two trials revealed that even the combination of death and myocardial infarction was significantly reduced by the use of enoxaparin. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin for the treatment of acute coronary syndromes and that they offer practical and therapeutic advantages.

Cardiac markers and risk stratification: an integrated approach.

Risk stratification of patients with acute coronary syndromes (ACS) is pivotal for correct allocation of health resources and for maximizing the benefit of available treatment modalities. However, clinical and electrocardiographic indicators of high risk lack sufficient sensitivity for the detection of major cardiac events. The complementary information provided by the measurement of different biomarkers is believed to be very useful. Specifically, elevations of cardiac troponin I (cTnI) and T (cTnT) are strongly associated with a high-risk profile both at short- and long-term. This has been definitely demonstrated in many studies as well as in cumulative meta-analysis. The role of different biomarkers, such as those reflecting activation of hemostasis and the presence of inflammation, is however less defined. At the moment, no study has prospectively evaluated these biomarkers in the whole spectrum of unselected patients with ACS. It is also unclear whether these biomarkers add independent prognostic value to the clinical and electrocardiographic indicators of adverse outcome and whether they offer additional information when compared to each other. The Early Prognostic Value of Biochemical Markers of Myocardial Damage, Activation of Hemostatic Mechanism and Inflammation in Acute Ischemic Syndromes (EMAI) study has been prospectively designed to solve these issues. In this study, we have evaluated the prognostic value of cTnI and cTnT, D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and C-reactive protein (CRP) in patients with ACS at the time of admission. We have enrolled in 31 Italian Coronary Care Units 1971 patients with rest anginal pain within 12 h from admission and electrocardiographic evidence of myocardial ischemia. Of these, 730 patients resulted to have ST-segment elevation myocardial infarction eligible for a reperfusion strategy and 1241, an acute coronary syndrome without persisting ST-segment elevation. Primary outcome measure of the study is the composite of death and non-fatal MI within 30 days from admission, which has occurred in 8.9% of the study population.

Prognostic role of hemostatic markers in acute coronary syndromes patients.

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult in part because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with highest levels had a twofold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. The results suggest that: (1) the detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurements of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes.

BACKGROUND: Elevations of cardiac troponin T or I are predictive of adverse outcomes in patients with acute coronary syndromes. However, odds ratios (ORs) vary substantially between studies. This investigation refines these values by means of a meta-analysis. METHODS: Twenty-one studies were suitable. ORs were calculated for short-term (30 days) and long-term (5 months to 3 years) follow-up in patients with ST-segment elevation (ST upward arrow), in those without ST-segment elevation (no ST upward arrow), and in patients with unstable angina. The primary end point was a composite of death or nonfatal myocardial infarction. RESULTS: A total of 18,982 patients were included. At 30 days, the OR for death or myocardial infarction was 3.44 (95% confidence interval [CI], 2.94-4.03; P <. 00001) for patients with positive troponin. In the ST upward arrow group, troponin elevations carried a 2.86-fold (95% CI, 2.35-3.47; P <.0001) higher risk during short-term follow-up, which was maintained long term. The no-ST upward arrow patients with troponin elevations manifested a 4.93-fold (95% CI, 3.77-6.45; P <.0001) increase of adverse outcomes. The OR for patients with unstable angina and positive troponin was 9.39 (95% CI, 6.46-13.67; P <.0001). For cardiac death alone, the results were similar. CONCLUSIONS: Patients with acute coronary syndromes who have troponin elevations show a substantial increase in risk during short and long-term follow-up.

In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris.

In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1+2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving either recombinant hirudin (31 patients) or heparin (36 patients). Blood samples were obtained at baseline (before any treatment), after 3 to 5 days of study drug infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drug discontinuation were significantly lower than at baseline (P:=0.0014), whereas they had not changed in the patients receiving heparin; at this time point, the difference between patients receiving hirudin and those receiving heparin was statistically significant (P:=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were similarly persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion were significantly lower than at baseline in both treatment groups (P:=0. 0005 for hirudin and P:=0.042 for heparin) and remained lower after 1 month (P:=0.0001 for both hirudin and heparin). The fibrinopeptide A plasma levels were not different between patients treated with hirudin versus heparin at baseline, at the end of infusion, and after 1 month. Thus, in patients with unstable angina, in vivo thrombin generation and activity are reduced during intravenous infusion of recombinant hirudin. However, the inhibition of thrombin generation is not sustained, and after 1 month, the majority of patients have biochemical signs of increased thrombin generation.

[The role of biochemical markers of myocardial damage in clinical practice: the diagnosis of infarct and risk stratification. The Intersociety Interdisciplinary Study Group of the ANMCO-SIBioC-SIMeL, Markers of Muocardial Lesions. L'Associazione Nazionale Medici Cardiologi Ospedalieri-Società Italiana di Biochimica Clinica-Società Italiana di Medicina di Laboratorio]. / Ruolo dei marcatori biochimici di danno miocardico nella pratica clinica: diagnosi di infarto e stratificazione del rischio. Gruppo di Studio Interdisciplinare Intersocietario ANMCO-SIBioC-SIMeL "Marcatori di Lesione Miocardica".

For many years creatine kinase (CK) and CK-MB isoenzymes were used together with the ECG to confirm the presence of myocardial infarction. During the last decade newer cardiac markers have been introduced and immunological test systems developed for their quantification. Among these new markers, a prominent role has emerged for cardiac troponins (T or I). These technological advanced assays have shown greater sensitivity compared to "conventional cardiac enzymes;, thereby identifying patients with small--at times, microscopic--infarcts who would not have met defining criteria for myocardial infarction in an earlier era. Another major advantage shown by both cardiac troponins with respect to "conventional cardiac enzymes" is their ability to predict clinical outcome over a short- or long-term follow-up in patients with acute coronary syndromes, and this appears to be particularly relevant in patients with micronecrosis, who constitute a high-risk subgroup of unstable angina patients. Recently, myoglobin has also been widely applied as a marker. Although lacking in myocardial specificity, it is the earliest marker to show an increase after coronary occlusion. Thus, the combined use of myoglobin and a cardiospecific structural protein such as troponin T or I may prove an attractive strategy for biochemical testing in chest pain patients. With the routine use of these novel cardiac markers, fascinating opportunities are now open in the field of diagnostic classification (making the World Health Organization definition of myocardial infarction obsolete) and risk stratification in chest pain patients; opportunities that were unforeseen in the era of cardiac enzymes. However, the use of these markers has also posed some important questions on: a) the best and most cost-effective diagnostic strategy in chest pain patients; b) the remaining role of cardiac enzymes; c) the therapeutic consequences of a positive test result.

Soluble E-selectin is not a marker of unstable coronary plaque in serum of patients with ischemic heart disease.

Increased level of soluble cell adhesion molecules may be a marker for atherosclerosis and/or reflect complication of the atherosclerotic plaque. To test whether expression of cell adhesion molecules is more pronounced in unstable versus stable coronary plaques, we measured the serum level of soluble E-selectin (sE-selectin) in 99 consecutive patients admitted to the hospital for acute coronary syndromes (ACS) and in 61 patients with chronic coronary artery disease (CAD) using a commercially available ELISA kit. We also measured the sE-selectin concentration in 20 sex- and age-matched subjects without clinical evidence of atherosclerosis, who served as controls. The mean sE-selectin level was higher in both groups of patients compared with controls (ACS, 35.0 +/- 23.4 ng/mL; chronic CAD, 32.9 +/- 21.0 ng/mL; controls, 14.5 +/- 6.6 ng/mL; one-way ANOVA, P = 0.001), but there was no difference between patients with ACS and chronic CAD. Furthermore, there was a trend (P = 0.08) toward a decrease in sE-selectin with an increase in the extent and severity of CAD. In patients with ACS, the in-hospital cardiac event rate was 8%. Although mean sE-selectin concentration tended to be higher in patients with (49.2 +/- 42.1 ng/mL) than in those without (33.8 +/- 21.3 ng/mL) in-hospital cardiac events, the difference was not significant. In 53 patients with ACS, C-reactive protein was measured and showed no correlation with the sE-selectin concentration. These findings show that although sE-selectin concentration is elevated in the presence of clinically relevant atherosclerosis, it does not further increase during the unstable phase of the disease, indicating that sE-selectin is not a reliable indicator of a complicated atherosclerotic plaque.

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Early risk stratification of unstable angina/non-Q myocardial infarction: biochemical markers of coronary thrombosis.

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult partly because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with the highest levels had a 2-fold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. These results suggest that: (1) The detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurement of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Clinical relevance of prodromal angina before acute myocardial infarction.

The term preconditioning was applied to the observation made in 1986 by Murry and colleagues that canine myocardium subjected to brief episodes of ischemia and reperfusion would tolerate a more prolonged episode of ischemia better than myocardium not previously exposed to ischemia. Since that seminal observation, protective effect of preconditioning was demonstrated in all animal species tested, resulting in the strongest form of in vivo protection against myocardial injury other than early reperfusion. Angina heralding acute myocardial infarction may represent the clinical correlate of preconditioning phenomenon in humans. Data from small pathophysiological studies demonstrated that prodromal angina (<48 hours prior to index myocardial infarction) causes a reduction of infarct size and consequently a better left ventricular function compared with patients without such clinical feature before myocardial infarction. The protective effect of prodromal angina was also confirmed in larger prospective studies; its presence translates into a significant reduction of a combination of death, cardiogenic shock and pulmonary edema during hospital stay. The exact mechanism of such clinical phenomenon is however not known, but it may include preconditioning. Other mechanisms have been also claimed to play an important role, like a more rapid lysis of the occlusive thrombus within the infarct-related artery, or a rapid opening of intramural collateral not visible at angiography. Whatever the mechanism, it appears that patients with prodromal angina before myocardial infarction exhibit, when rapidly reperfused, a better post-infarction clinical outcome. At the present "optimal preconditioning-mimetic agents" are yet to be found, and "putting preconditioning in a bottle" still remains a pharmacologic challenge.

Direct comparison of early elevations of cardiac troponin T and I in patients with clinical unstable angina.

BACKGROUND: The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina. METHODS: We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.

[Platelet antiaggregants or anticoagulants in the secondary prevention after myocardial infarct]. / Antiaggreganti piastrinici o anticoagulanti nella prevenzione secondaria dopo infarto miocardico.

Aspirin and oral anticoagulants are effective treatments in the secondary prevention after myocardial infarction. Aspirin at the dosage of 160-325 mg per day accomplishes a 21% reduction of the recurrences of vascular events (INR: 3-4). Oral anticoagulants are likely to be more effective; this therapy however is more demanding for the patient and the referring physician and is associated with a higher risk of hemorrhage. According to the available information from the literature, aspirin should be recommended for the majority of patients surviving after myocardial infarction. Oral anticoagulants should be reserved for post-infarction patients at high risk of thromboembolism and for those patients who present either intolerance to aspirin or recurrence of vascular events during aspirin treatment.

New markers for early diagnosis of acute myocardial infarction.

The availability of 'new' biochemical markers of myocardial injury such as creatine kinase isoforms and troponins has renewed the interest for rapid confirmation/exclusion of myocardial infarction in patients presented to the hospital for suspected acute myocardial ischemia. Many of these protein markers have the potential to allow the diagnosis of acute myocardial infarction at a time from the onset of symptoms when the activity of creatine kinase MB is still within the reference range. However, the exclusion of classical myocardial infarction as defined by WHO criteria does not allow to conclude that the patient is at low-risk and can be safely sent home since he may have high-risk unstable angina. The sensitivity for the detection of myocardial damage of troponins is such that a substantial proportion of patients with unstable angina develop elevations of troponins in the absence of creatine kinase MB increases. It is now clear that such patients have an increased risk of cardiac events over the short and long-term similar to that of patients with definite myocardial infarction. Such finding may help in developing selective admission policies and deciding which patients deserve aggressive treatment.

Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina.

BACKGROUND: Elevations of the MB isoform of creatine kinase (CK) and cardiac troponin T seem to confer an adverse prognosis in unstable angina. We examined whether this prognostic influence is also present for cardiac troponin I (cTnI), a new and even more specific marker of myocardial injury. METHODS AND RESULTS: We studied 106 patients with the clinical diagnosis of unstable angina showing chest discomfort at rest within 48 hours of admission, ECG evidence of myocardial ischemia, and normal values of total CK over the initial 16 hours of observation. The primary end point was death or nonfatal myocardial infarction (MI) at 30 days; the secondary end point was the incidence of cardiac events at 1 year. Blood was drawn every 8 hours for 3 days. Thirteen patients were excluded because of increased CK-MB mass concentrations within 16 hours of admission (non-Q-wave MI) and 2 because of inadequate blood sampling. Of the remaining 91 patients, 22 had cTnI elevations on admission (n=7) or after 8 hours (n=15). At 30 days, no deaths (0%) and 4 MIs (5.8%) occurred in the 69 patients with normal cTnI compared with 2 deaths (9.1%) and 4 MIs (18.2%) in the 22 patients with elevated cTnI. The combined incidence of death and nonfatal MI was 5.8% and 27.3%, respectively (P=.02). At 1 year, only 68% of patients with elevated cTnI were free of cardiac events, compared with 90% of those without elevations (P=.01). CONCLUSIONS: These data indicate that cTnI is an important prognostic variable in patients with unstable angina. Elevations of cTnI predict an adverse short- and long-term prognosis.

The importance of antibody specificity in measuring cross-linked fibrin degradation products by ELISA.

We and others have previously shown that plasma concentrations of XL-FDPs are accurately characterized with an enzyme-linked immunosorbent assay (ELISA) based on the monoclonal antibody DD-3B6/22, which is specific for D-dimer, and a pan-specific tag antibody (DD-4D2/182) in patients with thrombotic disorders. However, in patients treated with fibrinolytic agents, increases in non-cross-linked fibrin(ogen) degradation products are detected by the pan-specific tag antibody due to formation of complexes between non-cross-linked derivatives and XL-FDPs. Assays based on the use of fibrin degradation product-specific tag antibodies appear to be more specific, but whether they would be clinically more informative is unclear. Accordingly, in the current study we measured concentrations of XL-FDPs with two ELISAs; one based on the pan-specific tag antibody (DD-4D2/182) and another based on a fibrin degradation product-specific tag antibody (DD-1D2/48) in patients treated with three well-characterized thrombolytic regimens: one associated with minimal fibrinogenolysis (100 mg tissue-type plasminogen activator [t-PA]) over 3 h), moderate fibrinogenolysis (100 mg t-PA over 90 min), and one with marked fibrinogenolysis (1.5 MU streptokinase [SK]). In patients treated with t-PA, increases in XL-FDPs were closely correlated with fibrinogenolysis, as characterized by increases in the concentration of the Bbeta1-42 peptide, when measured with the pan-specific tag ELISA (r = 0.7), but not when measured with the fibrin degradation product-specific tag assay (r = 0.2). In patients treated with SK, concentrations of XL-FDPs were significantly higher (> 2000 ng/ml) with the pan-specific tag ELISA compared with the fibrin degradation product-specific tag ELISA (< 1000 ng/ml) 1, 2 and 8 h after start of the infusion (P < 0.01). Concentrations of XL-FDPs were also higher in patients treated with SK compared with t-PA when measured with the pan-specific tag ELISA, but lower with SK with the fibrin-specific ELISA (P < 0.01). The value of measurement of XL-FDPs in patients treated with fibrinolytic agents will need to be reappraised with the use of fibrin degradation product-specific assays, which appear to provide more accurate information on the kinetics of cross-linked fibrin lysis in patients treated with t-PA or SK.