fibrinopeptide-a and Myocardial-Ischemia

Intracoronary thrombus formation has been thought to play an important role in the genesis of acute myocardial infarction an unstable angina. To examine whether the coagulation and fibrinolytic systems are altered in such ischemic heart diseases, the plasma levels of fibrinopeptide A (FPA) and plasminogen activator (PAI) were measured. The plasma level of FPA was increased in patients with variant angina as compared with those with stable exertional angina and there was a significant circadian variation in the plasma level of FPA in parallel with that of the frequency of the attacks with the peak level occurring from midnight to early morning in patients with variant angina. The plasma FPA level increased in patients with coronary spastic angina after the ischemic attack induced by hyperventilation. Furthermore, FPA was released into the coronary circulation after the anginal attack induced by intracoronary injection of acetylcholine. These findings suggest that the coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery. On the other hand, the plasma level of PAI activity was higher in patients with unstable angina and coronary spastic angina than in those with stable exertional angina. Moreover, the PAI activity in patients with unstable angina decreased to the level in patients with stable exertional angina after the stabilization of their symptoms by drugs. Our findings suggest that the increased plasma PAI activity may reduce fibrinolytic activity and attenuate removal of the thrombus and may ultimately lead to acute myocardial infarction in some patients with unstable angina and coronary spastic angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angina, Unstable; Fibrinopeptide A; Humans; Myocardial Ischemia; Plasminogen Activators

We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion.. We evaluated protein C activation during cardiopulmonary bypass and coronary reperfusion in 20 patients undergoing coronary bypass surgery. During cardiopulmonary bypass and during the 10 minutes after aortic unclamping, the plasma levels of protein C (mean +/- standard error of the mean) decreased from 123% +/- 7% to 74% +/- 5% of normal mean. In contrast, the levels of activated protein C in plasma increased from 122% +/- 8% to 159% +/- 21%, and the activated protein C/protein C ratio increased from 1.04 +/- 0.08 to 2.29 +/- 0. 31 (P =.006, 2-tailed Wilcoxon signed rank test). Patients were stratified on the basis of the increase in activated protein C in the coronary sinus plasma at 10 minutes after reperfusion by means of the arbitrary value of 1.5 for the activated protein C/protein C ratio. Within 24 hours, the patients with low increases in activated protein C (ratio < 1.5, n = 8) had a significantly (P <.05) lower cardiac output and mean pulmonary artery pressure, as well as a higher systemic vascular resistance, than patients (n = 11) with high increases in activated protein C (ratio > 1.5). The rapid increase in activated protein C during the first 10 minutes after aortic unclamping indicated protein C activation in the reperfused vascular beds.. The antithrombotic protein C pathway was significantly activated during cardiopulmonary bypass mainly during the minutes after aortic unclamping in the ischemic vascular beds. Suboptimal protein C activation during ischemia may impair the postischemic recovery of human heart and circulation.

Topics: Adult; Aged; Antioxidants; Biomarkers; Cardioplegic Solutions; Cardiopulmonary Bypass; Catechol O-Methyltransferase Inhibitors; Catechols; Coronary Artery Bypass; Fibrinolytic Agents; Fibrinopeptide A; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Pentanones; Protein C; Protein S

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1 + 2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5 +/- 0.6 g/l vs. 3.3 +/- 0.5 g/l, P < 0.001), prothrombin fragment 1 + 2 (1.4 +/- 0.5 nmol/l vs. 1.9 +/- 0.7 nmol/l, P < 0.001), thrombinantithrombin (4.5 +/- 2.4 ng/ml vs. 9.7 +/- 3.6 ng/ml, P < 0.001), and fibrinopeptide A (2.1 +/- 1.1 ng/ml vs. 3.5 +/- 2.1 ng/ml, P < 0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.

Topics: Aged; Anticoagulants; Antithrombin III; Chronic Disease; Cross-Over Studies; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Peptide Hydrolases; Protein Precursors; Prothrombin; Thrombin

Mechanisms of restenosis after percutaneous transluminal coronary angioplasty (PTCA) have not been defined yet. Experimental studies have shown that thrombin, by stimulating platelet growth factor secretion and smooth muscle cell proliferation, can play a major role.. In 34 patients with single-vessel coronary disease undergoing PTCA, thrombin activity was evaluated through serial fibrinopeptide A (FPA) plasma determinations. Samples were performed before PTCA, immediately after and 24 hours, 72 hours, and 6 months later. Patients were grouped according to the development (group 1, n = 13) or nondevelopment (group 2, n = 21 ) of restenosis at a 6-month angiographic control. No difference in the two groups was found concerning baseline FPA values. In patients in group 1, soon after PTCA higher FPA levels (27.3 +/- 13.7 ng/ml) than those in group 2 (9.2 +/- 5.6 ng/ml; p < 0.05 vs pre-PTCA, and p < 0.01 between the two groups) were observed. No differences in FPA levels were detected at the other steps between the two groups.. Our data suggest that thrombin plays a role in the process of restenosis after PTCA; acute FPA response to the procedure seems to have a predictive value.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Ischemia; Recurrence; Thrombin; Time Factors

Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes.. Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA).. FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups.. IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Topics: Angina, Unstable; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Humans; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Prothrombin; Statistics, Nonparametric; Thrombin

Acute thrombosis is thought to contribute to abrupt coronary occlusion during percutaneous coronary revascularization despite the administration of heparin and aspirin. This study was designed to detect the presence of heparin-resistant thrombin activity and to define its relationship to the acute ischemic complications of coronary interventions.. Plasma levels of fibrinopeptide A (FPA) and prothrombin fragment 1.2 (F1.2), markers of thrombin and factor Xa activity, respectively, were measured in the coronary sinus with heparin-bonded catheters in 58 patients undergoing coronary interventions. Activated coagulation times were maintained > 300 seconds by the Hemochron method. Mean FPA levels decreased significantly, from 7.0 +/- 0.9 nmol/L before the procedure to 5.2 +/- 0.5 nmol/L after the heparin bolus and to 2.9 +/- 0.2 nmol/L after the procedure (P = .0001). In 26 patients (45%), FPA levels remained above the threshold for suppression angioplasty of thrombin activity determined during angiography in 7 patients without coronary artery disease (> 3.0 nmol/L). FPA concentrations after coronary interventions were increased in patients with intracoronary thrombus (P = .01), abrupt coronary occlusion (P = .06), postprocedural non-Q-wave myocardial infarction (P = .04), and clinically unsuccessful procedures (P = .04). F1.2 levels were relatively low before the procedures and did not change significantly.. Heparin administration suppresses thrombin activity in most but not all patients undergoing coronary interventions. Heparin-resistant thrombin activity is associated with angiographic evidence of intracoronary thrombus and ischemic complications of coronary interventions.

Topics: Acute Disease; Aged; Angiography; Blood Specimen Collection; Cardiac Catheterization; Factor Xa Inhibitors; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Prothrombin; Reproducibility of Results; Thrombin; Thrombosis; Whole Blood Coagulation Time

The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy.. Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median aPTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P < .0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P < .0002). Modified antithrombin III decreased over time (P < .002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P < .001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C.. This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.

Topics: Aged; Angina, Unstable; Blood Coagulation Factors; Blood Coagulation Tests; Coronary Thrombosis; Electrocardiography; Female; Fibrinopeptide A; Heparin; Humans; Infusions, Intravenous; Male; Monitoring, Physiologic; Myocardial Infarction; Myocardial Ischemia; Protein C; Substance Withdrawal Syndrome; Thrombin; Thrombosis

Venous occlusion (VO) during which thrombin (Th) is postulated to be generated is routinely used for evaluation of fibrinolytic potential of endothelium (E). This study was performed to find out whether VO can also be used for assessment of anticoagulant function of E. VO was performed in 98 male patients (pts) with ischemic heart disease. Levels of protein C (PrC) which is related to Th binding by thrombomodulin and fibrinopeptide A (FpA)--a marker of presence of free Th--were determined together with some other factors of coagulation and fibrinolysis. Differences between pre- and postVO PrC levels fluctuated from -54.8% to +57.3%. According to reaction of PrC to VO pts were divided into 2 groups: 13 pts with increase or no change and 17 pts with decrease (consumption) of PrC. In pts without PrC consumption there was a significant increase in FpA. In pts with PrC consumption FpA was unchanged. In pts with PrC consumption exceeding its median value for this group (14%) PAI-1 antigen level fell significantly (-8.4 + 4%) during VO. Thus PrC consumption after VO indicates that TH is effectively removed from blood stream by endothelial factors. Absence of consumption of PrC is a sign of ineffective anticoagulant function of E. Increase in PrC level during VO in some pts may be due to its escape from tissue depot.

Topics: Adult; Arm; Blood Coagulation Tests; Endothelium, Vascular; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Ischemia; Protein C; Tourniquets; Veins