fibrinopeptide-a and Coronary-Disease

Topics: Acute Disease; Blood Coagulation; Coronary Disease; Death, Sudden, Cardiac; Fibrinolysis; Fibrinopeptide A; Humans; Plasminogen Inactivators

The interaction between blood factors and the vessel wall is important in the development of common cardiovascular diseases. Clinical markers of these interactions should be sought to help in the understanding of the processes involved, and such markers should ideally be available to identify people at risk from the disease, screen relatives, help identify appropriate treatment, and monitor the outcome of the therapy. Various aspects of platelet interaction with the vessel wall can be used, as can some changes in levels of coagulation factors, fibrinolytic proteins, and natural anticoagulants. All have their advantages and disadvantages in terms of having the attributes of the ideal marker that would identify the pathophysiological processes and be reproducible, inexpensive, and easy to perform. This review will consider the value of various clinical markers, taking account of their advantages and disadvantages.

Topics: beta-Thromboglobulin; Blood Coagulation Factors; Blood Platelets; Coronary Disease; Coronary Thrombosis; Fibrinolysin; Fibrinolysis; Fibrinopeptide A; Humans; Muscle, Smooth, Vascular; Plasminogen; Platelet Aggregation; Platelet Factor 4; Thrombosis; Thromboxane B2

Topics: Angina Pectoris; Blood Coagulation Disorders; Blood Platelet Disorders; Coronary Disease; Coronary Vasospasm; Fibrinopeptide A; Humans; Myocardial Infarction; Prostaglandins; Thromboxanes

Effects of aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. This study analyses hemostasiologic changes and potential benefit in OPCAB patients treated with aprotinin.. In a prospective, double-blind, randomized study 47 patients undergoing OPCAB surgery were investigated. Patients received either aprotinin (2 x 10(6) KIU loading dose and 0.5 x 10(6) KIU/h during surgery, n=22) or saline solution (control, n=25). Activated clotting time was adjusted to a target of 250 s intraoperatively. Blood samples were taken up to 18h postoperatively: complete hematologic and hemostasiologic parameters including fibrinopeptide A (FPA) and D-dimer in a subgroup of 31 patients were analyzed. Blood loss, blood transfusion and other clinical data were collected.. Both groups showed comparable demographic and intraoperative variables. Forty-one (87%) patients of the whole study group received aspirin within 7 days prior to surgery. Number of grafts per patient were comparable (2.9+/-1.0 [mean+/-SD] in the aprotinin group and 2.8+/-1.2 in control, P=0.83). Blood loss during the first 18 h in intensive care unit was significantly reduced in patients treated with aprotinin (median [25th-75th percentiles]: 500 [395-755] ml vs. 930 [800-1170] ml, P<0.001). Postoperatively only two patients (10%) in the aprotinin group received packed red blood cells, whereas eight (35%) in the control group (P=0.07). Perioperatively FPA levels reflecting thrombin generation were elevated in both groups. The increase in D-dimer levels after surgery was significantly inhibited in the aprotinin group (P<0.001). Early clinical outcome was similar in both groups.. Aprotinin significantly reduces blood loss in patients undergoing OPCAB surgery. Inhibition of enhanced fibrinolysis can be observed. FPA generation during and after OPCAB surgery seems not to be influenced by aprotinin.

Topics: Aged; Analysis of Variance; Aprotinin; Chi-Square Distribution; Coronary Artery Bypass; Coronary Disease; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Postoperative Hemorrhage; Prospective Studies; Protease Inhibitors; Statistics, Nonparametric

Thrombus is important in the pathophysiology of several complications of angioplasty, including abrupt closure and restenosis. Levels of prothrombin fragment F1.2 and fibrinopeptide A reflect thrombin generation and activity. The effect of angioplasty on levels of these markers is unclear.. Patients undergoing either balloon angioplasty (n = 30) or directional atherectomy (n = 9) were treated with heparin to maintain an activated clotting time of >300 seconds. Levels of F1.2, fibrinopeptide A, and thrombin-antithrombin complex were measured in the coronary sinus and coronary artery before and after intervention. Angiograms were reviewed for lesion morphologic characteristics and dissection.. There was no evidence for thrombin generation or increased thrombin activity after angioplasty regardless of lesion morphologic characteristics, dissection, type of intervention, or blood sampling site. In fact, coronary sinus concentrations of F1.2 decreased after intervention (median 0.31 nmol/L; 25th percentile 0.26 nmol/L, 75th percentile 0.37 nmol/L) before intervention to 0.23 nmol/L (25th percentile 0.19 nmol/L, 75th percentile 0.34 nmol/L) after intervention (P =.002).. Angioplasty performed in the presence of adequate heparin inhibited thrombin even when there was complex lesion morphology or dissection. These data suggest that heparin provides satisfactory thrombin inhibition during routine angioplasty.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombin III; Atherectomy, Coronary; Coronary Angiography; Coronary Disease; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Prothrombin; Thrombin

The influence of a moderate dietary supplementation with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (3.4 g eicosapentaenoic and docosahexaenoic acids per day) for six months on lipopolysaccharide (LPS) stimulated monocyte procoagulant activity (PCA) was studied in two series of experiments, evaluating the plasma and cellular phases, respectively. In the first series, standard cryopreserved monocyte cultures were examined in heparin plasma of atherosclerotic patients (n = 24, 12 given omega-3 PUFAs, 12 controls). In the second series, monocytes from patients (n = 32, 16 given omega-3 PUFAs, 16 controls) were investigated in a standard plasma milieu. Plasma and monocytes were obtained from the test subjects before as well as after six months of omega-3 PUFA supplementation. Monocyte PCA, measured by the formation of fibrinopeptide A, was not significantly different when comparing plasma and monocytes from the subjects supplemented with omega-3 PUFAs with plasma and monocytes, respectively, from the control subjects. In the second series of experiments we also determined the LPS induced release of interleukin-6 (IL-6), which was not significantly different in the two groups. However, a strong correlation between the stimulated monocyte IL-6 release and PCA was demonstrated (r = 0.70, p = 0.00001), probably reflecting an individual inflammatory response pattern.

Topics: Arachidonic Acid; Blood Coagulation; Coronary Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fibrinopeptide A; Humans; Interleukin-6; Monocytes

This prospective, randomized study involving patients undergoing isolated coronary artery bypass grafting investigated whether the use of heparin-coated bypass circuits with an uncoated cardiotomy reservoir (n = 10) compared with standard uncoated bypass circuits (n = 10) resulted in differences in patient outcome and hemostatic alterations. There were no differences in postoperative blood loss, transfusion requirements, and routine coagulation test results between groups. Immunoassays for platelet alpha-granule constituents platelet factor 4 and beta-thromboglobulin, thrombin generation by-product F1.2, fibrinopeptide A, thrombin-antithrombin complex, and fibrinolysis by-product D-dimer also demonstrated no significant differences between groups, although trends for lower platelet secretion with heparin coating were noted. Increases were found in beta-thromboglobulin and platelet factor 4 concentrations at 10 (p < 0.03) and 30 minutes (p < 0.001) of CPB, respectively, and continuing throughout CPB (p < 0.001) for both groups versus values measured before incision. No significant differences were seen between levels 5 minutes prior to aortic cross-clamp release and those obtained 8 and 45 minutes after cross-clamp release. Conversely, no significant increases in F1.2, thrombin-antithrombin complex, and D-dimer were seen prior to release of the aortic cross-clamp, but afterward increases occurred that were highly significant (p < 0.001). The temporal data suggest that platelet activation occurs primarily as a result of contact with the cardiopulmonary bypass circuitry, whereas thrombin generation and fibrinolytic activity are not significant until reperfusion of the heart and lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antithrombin III; beta-Thromboglobulin; Blood Coagulation Tests; Blood Loss, Surgical; Cardiopulmonary Bypass; Constriction; Coronary Disease; Coronary Vessels; Female; Fibrinopeptide A; Hemostasis; Hemostasis, Surgical; Heparin; Humans; Male; Middle Aged; Peptide Hydrolases; Platelet Factor 4; Postoperative Care; Preoperative Care; Prospective Studies; Surface Properties

The platelet-aggregatory response, platelet-release factors and markers of thrombin generation in vivo were studied prospectively in 53 patients participating in a randomized clinical trial evaluating the influence of nicardipine on the progression of coronary atherosclerosis. Coronary lesions were measured quantitatively and progression was defined as a decrease in minimum diameter by > or = 0.4 mm. At repeat angiography 24 months after study entry, 20 of the 53 patients had progression of 28 coronary narrowings. Only thrombin-induced enhanced platelet aggregation differentiated patients with from those without coronary disease progression, with an estimated odds ratio of 2.49 (95% confidence interval 1.10 to 5.66). The aggregatory response to adenosine diphosphate, collagen, epinephrine and platelet-activating factor were not different in the 2 groups of patients, nor were measurements of platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-prostaglandin F1 alpha and fibrinopeptide A. During 46.8 months of follow-up after repeat angiography, coronary events occurred in 11 of the 20 with and 6 of the 33 without progression (difference 37%, p = 0.013, confidence interval 11 to 63%). Those with coronary disease progression and an enhanced thrombin-induced platelet aggregation had a worse prognosis than those with no disease progression and a low thrombin-induced platelet aggregation. Thus, patients with coronary disease progression and future coronary events have an enhanced thrombin-induced platelet aggregation. This platelet abnormality may be a marker of increased risk and may play a causative role in the development of coronary events.

Topics: 6-Ketoprostaglandin F1 alpha; beta-Thromboglobulin; Coronary Angiography; Coronary Disease; Double-Blind Method; Female; Fibrinopeptide A; Follow-Up Studies; Humans; Male; Middle Aged; Nicardipine; Placebos; Platelet Aggregation; Platelet Factor 4; Prospective Studies; Survival Rate; Thrombin; Thromboxane B2

Sixty-four patients undergoing aorto-coronary bypass surgery were randomized to receive antithrombotic treatment with acetylsalicylic acid (ASA), 300 mg/d (n = 30) or warfarin, INR = 2.5 - 4.2 (n = 34). The levels of fibrinogen, thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA) and D-dimer were assessed before surgery and 9 months postoperatively. In the warfarin treated group the fibrinogen levels were increased after 9 months, while the levels of TAT, FPA and D-dimer were decreased. In the ASA group TAT levels were increased at 9 months, whereas no significant changes in fibrinogen, FPA or D-dimer from baseline were noted. Thus, a reduced activation of the coagulation system has been demonstrated during long-term treatment with warfarin in patients with coronary artery disease.

Topics: Adult; Aged; Antithrombin III; Combined Modality Therapy; Coronary Artery Bypass; Coronary Disease; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Middle Aged; Peptide Hydrolases; Time Factors; Warfarin

The relations of plasma activated factor XII (FXIIa) concentration and a common polymorphism (C46T) of the factor XII gene with hemostatic status and risk of coronary heart disease (CHD) were examined by prospective surveillance.. Genotyping for the C46T variant was performed in 2624 men 50 to 61 years of age who were free of CHD at baseline. The genotype distribution was as follows: CC, 56.7%; CT; 36.9%; and TT, 6.6%. Plasma FXIIa was measured by ELISA on 1745 samples collected 1 year after baseline; median levels were (ng/mL) CC, 2.0; CT, 1.4; and TT, 0.8 (P:<0.0001). Respective values for plasma fibrinopeptide A (FPA, nmol/L) were 1.52, 1.35, and 1.15 (P:<0.0001); for factor VII coagulant activity (FVIIc, % standard), 114.5, 116.2, and 109.3 (P:=0.02). Group differences in FVIIc were unchanged by adjustment for body mass index and serum triglycerides. Whereas CHD incidence did not differ significantly by genotype, rates (per 1000 person-years) by thirds of FXIIa distribution were for <1.5 ng/mL, 7. 2; for 1.5 to 2.0 ng/mL, 7.2; and for >2.0 ng/mL, 13.6. Respective hazard ratios with the low third as reference group were 1.01 and 1. 96 (P:=0.007), which were essentially unchanged after allowance for genotype, blood lipids, blood pressure, body mass index, FVIIc, and FPA.. The C46T polymorphism is a determinant of FXIIa, FPA, and possibly FVIIc, suggesting that FXII influences the activity state of the coagulation pathway and FPA cleavage from fibrinogen in vivo. Plasma FXIIa is increased in middle-aged men at high risk of CHD.

Topics: Biomarkers; Coronary Disease; Factor VII; Factor XIIa; Fibrinopeptide A; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Risk Factors

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

This study was designed to characterize hemostatic activation (using fibrinopeptide A (FPA), a marker of thrombin activity, and beta-thromboglobulin (BTG), a marker of platelet activation) sequentially in the coronary and peripheral circulation in patients during percutaneous coronary intervention (PCI) and several hours after PCI and discontinuation of heparin therapy. Heparin administered during PCI is known to nonuniformly suppress thrombin activity in the coronary. Persistent elevations of FPA in coronary sinus (CS) blood during PCI have been associated with subsequent ischemic events. As a related consideration, rebound thrombin activity has been demonstrated in peripheral blood samples several hours after cessation of heparin therapy in patients with acute coronary syndromes. Accordingly, we hypothesized that increased thrombin activity occurs in the coronary circulation after PCI and is induced by cessation of intravenous heparin to facilitate vascular sheath removal. Such a rebound prothrombotic effect, may contribute to suboptimal outcomes after PCI. In 21 patients undergoing PCI, heparin-bonded catheters were employed to obtain sequential CS and femoral vein (FV) blood samples for measurement in the coronary and peripheral circulation of plasma FPA, a marker of thrombin activity in vivo, and BTG released by platelets during degranulation. Following heparin administration samples were obtained immediately prior to (base) and during (start and end) PCI. Late samples were obtained several hours after PCI (284 +/- 46 min, mean +/- SD) following the cessation of heparin and prior to planned vascular sheath removal. Mean FPA concentration in CS blood was low at baseline (3.82 +/- 2.09 ng/ml) and did not increase during PCI. Mean FPA concentration in CS blood increased significantly several hours after cessation of heparin (3.42 +/- 2.36 vs. 7.82 +/- 9.98, end vs. late, P < 0.001). In contrast, mean FPA concentration in FV blood was highest at baseline following vascular sheath insertion, decreased during PCI (69%, P < 0.05, base vs. end), and trended upward after PCI and cessation of heparin. Mean FPA values were higher at all times in FV compared with CS blood samples and were not concordant after PCI. Elevation of coronary circulation FPA after PCI was maximal in patients with myocardial infarction within 7 days (13.7 +/- 12.4 vs. 5.6 +/- 7.9 ng/ml, P = 0.08), but was not influenced by heparin treatment prior to PCI, a history of unstable angina, or

Topics: Aged; Anticoagulants; beta-Thromboglobulin; Coronary Disease; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Thrombin; Treatment Outcome

Endothelial cells, circulating platelets, and proteins of the coagulation and fibrinolytic systems are known to contribute to the hemostatic processes. Various molecular markers of hemostatic alteration are found in increased amounts in the circulation during the activation of this process. In this study, we investigated serum lipoprotein (a) and plasma platelet factor 4, beta-thromboglobulin, thrombin-anthithrombin complex, fibrinopeptid A, D-dimer, tissue plasminogen activator, tissue plasminogen activator inhibitor, and fibronectin levels in patients with coronary artery disease. The levels of all these markers were found to be significantly higher as compared to the control group. Our findings suggest that patients with coronary artery disease have greater blood coagulability than controls, and the use of molecular markers has become greatly important in clinical practice.

Topics: Adult; Antithrombin III; beta-Thromboglobulin; Biomarkers; Coronary Disease; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibronectins; Hemostasis; Humans; Lipoprotein(a); Male; Middle Aged; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Platelet Factor 4; Tissue Plasminogen Activator

Despite anticoagulant therapy, intracoronary thrombus formation can accompany or be induced by percutaneous transluminal coronary angioplasty (PTCA). Clinical trials for the assessment of the efficacy of novel prophylactic regimens are expensive and difficult. Accordingly, we sought to develop an approach for investigating thrombogenesis accompanying PTCA that would facilitate the assessment of protective regimens in a relatively small number of patients.. Markers of in-vivo generation and activity of thrombin with plasma fibrinopeptide A (FPA) and platelet degranulation with beta-thromboglobulin (BTG) were measured in coronary sinus blood in patients undergoing PTCA. In an initial pilot study, we obtained peripheral venous blood samples through heparin-bonded sampling catheters to determine whether sampling affected values of the markers measured. We then measured FPA and BTG in coronary sinus blood samples, obtained from patients undergoing coronary angiography, to define the effects of injections of contrast media. Subsequently, we studied nine patients undergoing elective PTCA. Coronary sinus FPA and BTG were measured serially under baseline conditions during and after the procedure.. The catheters used elicited negligible effects on FPA and BTG values over a 30 min sampling interval. Similarly, coronary angiography had no detectable effect on coronary sinus FPA and BTG values. PTCA did not increase FPA (mean value at the conclusion of PTCA 1.17 +/- 0.31) or BTG (mean 30.9 +/- 15.9) in the PTCA group as a whole. However, in one patient the values increased markedly. For two patients, baseline values were elevated but declined with the re-establishment of brisk coronary flow after successful PTCA.. We have shown that coronary sinus samples can be obtained under conditions permitting assessment of ongoing thrombosis in patients undergoing PTCA. Samples can be obtained without introduction of artifactual elevations of FPA or BTG, facilitating assessment of the efficacy of novel antithrombotic regimens in preventing thrombogenesis otherwise seen in an important minority of patients undergoing coronary interventions.

Topics: Adult; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; beta-Thromboglobulin; Cardiac Catheterization; Coronary Angiography; Coronary Disease; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Activation; Thrombin

To determine whether, in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), there are prothrombotic markers indicating those with a predisposition to restenosis.. Venous blood samples were obtained from patients undergoing PTCA for chronic stable angina. Patients with restenotic lesions, conduit stenoses or occlusive lesions were not included in the study. Samples were assayed for coagulation factors (fibrinopeptide A, antithrombin III, protein C), fibrinolytic factors [tissue-type plasminogen activator (t-PA), alpha 2 antiplasmin, plasminogen activator inhibitor (PAI-1)] and markers of platelet activation (platelet factor 4, beta thromboglobulin).. Of 46 patients who underwent successful PTCA, restenosis, defined as loss in absolute gain of more than 50%, occurred in 16 (35%). The minimal luminal diameter (mean +/- SD) at follow-up in those who had suffered restenosis was 1.07 +/- 0.7 mm compared with 1.73 +/- 0.5 mm in the non-restenotic patients. However, no significant differences in the levels of markers of platelet activation, coagulation factors, or fibrinolytic factors were observed between the two groups. The only significant difference between the groups was a higher platelet count in the restenotic patients [median (interquartile range): 263 (247-278) versus 224 (175-263), P < 0.05].. Our results suggest that patients who suffer restenosis following PTCA appear to have no clearly detectable pre-existing imbalance in their prothrombotic/antithrombotic status. Although the platelet count was higher in restenotic patients, the levels of markers of platelet activation were no different in the two groups. Thus, it is at present unlikely that simple blood assays before PTCA assessing an individual's 'thrombotic state' can help to predict which of the 30-40% of patients undergoing PTCA will suffer restenosis.

Topics: alpha-2-Antiplasmin; Angina Pectoris; Angioplasty, Balloon, Coronary; Antithrombin III; beta-Thromboglobulin; Biomarkers; Coronary Angiography; Coronary Disease; Female; Fibrinopeptide A; Follow-Up Studies; Humans; Male; Middle Aged; Plasminogen; Plasminogen Activator Inhibitor 1; Platelet Factor 4; Protein C; Recurrence; Risk Factors; Thrombosis; Tissue Plasminogen Activator

Haemostatic and rheological factors may predict cardiovascular disease. We studied patients with intermittent claudication to see if the progression of peripheral arterial disease and the risks of coronary events could be predicted by baseline packed cell volume, plasma fibrinogen, blood and plasma viscosites, von Willebrand factor antigen, cross-linked fibrin degradation products (XLFDP), urinary fibrinopeptide A, and plasma leucocyte elastase. In 617 patients with claudication followed up for one year, baseline XLFDP was related most strongly to coronary events, relative risk 4.4 (95% CI 1.3-19.0) between top and bottom quintiles. Plasma fibrinogen was the strongest independent predictor of death from coronary disease. XLFDP was the only factor, in addition to age and cigarette smoking, that was independently associated (p = 0.008) with deterioration in peripheral arterial disease. We conclude that, in patients with peripheral arterial disease, plasma concentration of XLFDP, a measure of ongoing fibrin formation and degradation, is a strong predictor of both disease progression and future coronary risk. These results accord with the hypothesis that fibrin formation contributes to progression of coronary and peripheral atherosclerosis.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Blood Viscosity; Coronary Disease; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Hematocrit; Humans; Intermittent Claudication; Leukocytes; Male; Middle Aged; Pancreatic Elastase; Risk Factors; von Willebrand Factor

Fibrinopeptide A (FPA) is a small polypeptide cleaved from fibrinogen by thrombin, has a short half-life, and is considered a sensitive biochemical marker of thrombin activity, fibrin generation, and ongoing thrombosis. Increased plasma levels of FPA have been reported in various procoagulable and thrombotic medical and cardiovascular disorders, including acute myocardial infarction, unstable angina, and sudden cardiac death. However, activation of thrombosis by the arterial injury incurred during coronary angioplasty has not been systematically examined with use of plasma FPA measurements. To detect and monitor activation of thrombosis by coronary angioplasty, plasma levels of FPA were obtained by venipuncture and measured by radioimmunoassay before, immediately after, 24 to 48 h later, and 1 and 3 months after uncomplicated coronary angioplasty. From December 1990 through June 1991, FPA was measured in 30 patients (28 men and 2 women, aged 54 +/- 9 years) with coronary artery disease who were undergoing coronary angioplasty. The mean left ventricular ejection fraction was 55 +/- 7%. The dilated vessel was the left anterior descending coronary artery in 20 patients (together with a second vessel in 2), the right coronary artery in 9, and the left circumflex in 1. The procedure was successful and free of major complications in all patients. Before angioplasty the FPA levels averaged 6.50 +/- 1.18 ng/ml. Shortly after angioplasty they rose to 20.20 +/- 7.91 ng/ml (p = 0.08) despite intravenous heparin. At 24 to 48 h and after heparin had been discontinued for at least 4 h, the mean FPA levels were significantly higher (32.33 +/- 10.86 ng/ml) compared with baseline values (p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Thrombosis; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Radioimmunoassay; Risk Factors; Thrombin; Time Factors

Heparin is indispensable anticoagulant for cardiopulmonary bypass, but the dose of heparin is even now under discussion. In this study, hemostatic fluctuation was analyzed during and after the bypass using hemostatic molecular markers. The subjects were 16 adult cases of open heart surgery, 12 males, 4 females. The average age was 55.0 year. Operations were aortocoronary bypass in 12, valvular surgery in 3 and ASD patch closure in one with moderate hypothermic cardiopulmonary bypass. At the beginning of cardiopulmonary bypass, 3 mg/kg heparin was administered and the equivalent amount of protamine sulfate was used for neutralization at the end of the bypass. Platelet count, hematocrit, antithrombin III (ATIII), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, thrombin antithrombin III complex, FDP, D dimer FDP, plasmin alpha 2 plasmin inhibitor complex, tissue plasminogen activator (t-PA), and thrombomodulin (TM) were measured through the operation up to two weeks after surgery. ATIII decreased to 50% of control value all through the bypass. Platelet markers increased immediately, and the activated state continued 3 hours after the bypass. Coagulation markers increased markedly after the aortic declamping, and reached at its peak by three times as control value, immediately after the protamine neutralization and continued for 3 hours. During the bypass, fibrinogenolysis caused by t-PA which was stimulated by non-physiological circulation and stimulating substances, was observed. Fibrinolysis occurred following the hypercoagulability after the neutralization. TM was within normal range before the aortic declamping. But increased gradually after the declamp, and reached twice as much as the base line. It could be concluded that hypercoagulability and high platelet activation might play a role of perioperative thrombosis. Hypercoagulability and increase of serum TM would be related to reperfusion of the lung. The increasing of TM would reflect broad injury of vessel walls after the bypass, because plasma TM increased following the generalized injury of endothelial cells.

Topics: Adult; Aged; Antithrombin III; beta-Thromboglobulin; Blood Coagulation; Blood Coagulation Disorders; Cardiopulmonary Bypass; Coronary Disease; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hematocrit; Humans; Male; Middle Aged; Platelet Count; Receptors, Cell Surface; Receptors, Thrombin

A study of neurohumoral and functional determinants of the advance of Ischemic heart disease in 39 patients with unstable stenocardia with positive results of loading tests (transesophageal electrocardiostimulation and veloergometry) allowed to reveal a significant reduction of the coronary reserve and regional dysfunction of the myocardium that interrelated with changes of the prostacyclin/thromboxane balance, increase of vasopressin with unchanged angiotensin II value and increased marker of the functional state of thrombocytes--beta-thromboglobulin. These changes may be one of the leading links in the pathogenesis of destabilization.

Topics: Acute Disease; Angiotensin II; beta-Thromboglobulin; Coronary Disease; Epoprostenol; Fibrinopeptide A; Humans; Physical Exertion; Radioimmunoassay; Thromboxane A2; Vasopressins

Elevated levels of fibrin peptide A were found in venous occlusion only in the patients unconsuming C protein, which indicates that there is a relationship between the thrombin production processes during venous occlusion and the C protein system functioning, the anticoagulant function of the endothelium in particular. Moreover, this makes it possible to employ the standard venous occlusion test to make an integral assessment of endothelial function.

Topics: Adult; Blood Coagulation; Coronary Disease; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Protein C; Thrombin; Thrombophlebitis; Thrombosis; Tissue Plasminogen Activator

Fibrinopeptide A (FPA) levels were determined in 40 consecutive patients admitted to the coronary care unit with a typical history of chest pain: in 24 of them a diagnosis of acute myocardial infarction (AMI) and in 16 a diagnosis of angina was made. Seven of the patients with AMI suffered from recurrent episodes of early post-infarctional angina. FPA levels were determined in each patient on admission and every 4 h for 48 h. On admission in patients with both angina and AMI the FPA levels were significantly higher than in normal controls; these levels were higher in patients with AMI than in those with angina, but this difference was not significant. In patients with angina the values decreased progressively after 12 h to baseline values, while in those with AMI the high levels of FPA persisted throughout the 48-hour observation period. In many instances, particularly after 24 h, the differences between the two groups were statistically significant. In patients with early post-infarctional angina the episode of angor was preceded by or corresponded to a new great elevation of FPA levels. These data suggest that the thrombin generation is higher and more prolonged in patients with AMI than in those with angina; the determination of FPA levels, which are an index of 'in vivo' thrombin generation, can be useful to follow the clinical course of ischaemic heart disease.

Topics: Adult; Aged; Angina Pectoris; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction

Because acute coronary thrombosis can cause unstable coronary artery disease, fibrinopeptide A, a reliable marker of coagulation activity, may play a role in the evaluation of unstable ischemic syndromes. A new method of fibrinopeptide A sampling, spot urine normalized to urinary creatinine, was evaluated in patients with stable and unstable angina pectoris and acute myocardial infarction. Serial samples were obtained to characterize the changes in urinary fibrinopeptide A levels over time in patients with ischemic heart disease. Admission values (mean +/- SD) were similar in the control group (3.3 +/- 1.4 ng/mg creatinine) and the stable angina group (3.2 +/- 1.1 ng/mg creatinine) (p = NS). Values in the unstable angina group (5.7 +/- 2.6 ng/mg creatinine) were higher than those in the control (p = 0.008) and stable angina (p less than 0.001) groups. Myocardial infarction admission values (8.4 +/- 10.0 ng/mg creatinine) were higher than those in the control (p = 0.005) and stable angina (p less than 0.001) groups, but not higher than those in the unstable angina group. Peak values (the highest of multiple samples) were higher in the unstable angina group (7.6 +/- 5.9 ng/mg creatinine) than in the stable angina group (4.0 +/- 1.0 ng/mg creatinine) (p = 0.04), but not in the control group (4.5 +/- 1.9 ng/mg creatinine) (p = 0.056). The two patients with unstable angina with the highest peak values subsequently exhibited infarction. Peak values in patients with infarction (44.5 +/- 60.0 ng/mg creatinine) were significantly higher than those in patients with unstable (p = 0.03) or stable (p = 0.002) angina and control patients (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angina Pectoris; Angina, Unstable; Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies

Basal plasmin and thrombin activity in plasma were assessed by radioimmunoassay of the fibrinogen derivatives containing the sequence B beta 15-42 and of fibrinopeptide A respectively in a cross sectional controlled study of men with coronary artery disease. Compared with healthy controls (n = 33) men with angiographically defined coronary artery disease (n = 98) had a modest but significant increase in concentrations of fibrinopeptide A, indicating an activated coagulation system. Concentrations of B beta 15-42 were similar in those with coronary artery disease and in the controls. The enhanced thrombin activity in coronary artery disease is in keeping with current evidence suggesting an association between coronary artery disease and a hypercoagulable state.

Topics: Adult; Coronary Disease; Coronary Vessels; Cross-Sectional Studies; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Peptide Fragments; Scotland; Thrombin

In order to determine the role of thrombosis in the acute coronary syndromes the blood levels of fibrinopeptide A and protein C were examined with an enzyme-immune test in 48 patients treated in the cardiological clinic of the National Centre for Cardiovascular Diseases. 27 patients were with transmural myocardial infarction and 21 patients were with non-transmural myocardial infarction. The average time of the test from the onset of pain is 18.4 +/- 12.2 hours (from 3 up to 72 hours). The mean level for fibrinopeptide A for the whole group of patients is 4.95 +/- 3.1 ng/ml and that of protein C is 70.1 +/- 9.8%. For the group of patients with transmural myocardial infarction the level of fibrinopeptide A is 6.09 +/- 3.49 ng/ml and of protein C is 65.3 +/- 8.0%. For the patients with nontransmural myocardial infarction the levels are respectively 3.49 +/- 1.7 ng/ml for fibrinopeptide A and 76.3 +/- 8.3% for protein C. The difference between the two groups is statistically significant (p less than 0.005). In the patients with non-transmural myocardial infarction from whom the blood for the test was taken before the 24th hour the fibrinopeptide A level is 4.8 +/- 2.4 ng/ml and the protein C level is 69.0 +/- 7.8%. The deviations from the reference group are statistically significant (p less than 0.04). The practical importance of these results is discussed.

Topics: Acute Disease; Aged; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Protein C

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.

Topics: Aged; beta-Thromboglobulin; Blood Platelets; Calcium; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Female; Fibrin; Fibrinopeptide A; Humans; Male; Middle Aged

In this study, betathromboglobulin (BTG) and fibrinopeptide A (FPA) in peripheral venous blood were measured in 20 patients with stable angina pectoris before and immediately after exercise-induced myocardial ischaemia; in 5 of the 20 patients stable angina was associated with typical peripheral artery disease. A total of 10 patients with angiographically documented peripheral artery disease without angina and 10 normal volunteers were taken as control groups. BTG and FPA in the 15 patients with stable angina before exercise were 41 +/- 14 ng ml-1 and 2.3 +/- 0.9 ng ml-1 and were not statistically different from the values in normal controls; after exercise-induced myocardial ischaemia no significant increase occurred in these patients. Conversely, in the 5 patients with stable angina associated with peripheral artery disease BTG and FPA before exercise were 61 +/- 10 ng ml-1 and 3.5 +/- 0.8 ng ml-1 and increased to 114 +/- 14 ng ml-1 (P less than 0.001) and 4.1 +/- 0.5 ng ml-1 (P less than 0.01): These results were similar to those found in the 10 patients with isolated peripheral artery disease. We conclude that BTG and FPA in peripheral venous blood in patients with stable angina are not elevated either at rest or after exercise-induced myocardial ischaemia. Elevated values of BTG and FPA in patients with stable angina may reflect a major interaction between blood and atherosclerotic vessel wall, suggesting the presence of associated atherosclerotic lesions in peripheral artery disease.

Topics: Angina Pectoris; beta-Thromboglobulin; Coronary Disease; Fibrin; Fibrinopeptide A; Humans; Male; Physical Exertion; Platelet Aggregation

Plasma levels of B beta 15-42 peptide and fibrinopeptide A (FPA) were measured as indicators of plasmin-mediated fibrin(ogen)olysis and thrombin activity of fibrinogen in 34 middle-aged men, at rest and following a standard exercise test. In the group as a whole no significant changes in B beta 15-42 or FPA were noted after exercise. When the group was subdivided into men with (n = 20) and without (controls n = 14) coronary heart disease, exercise-stimulated thrombin and plasmin generation was found only in the control group who exercised for a significantly longer duration. The rise in B beta 15-42 was related to both the intensity and duration of exercise. Similar increases in plasma fibrinolytic activity (fibrin plate) occurred in both groups and no other differences in the components of the fibrinolytic system (plasminogen, alpha 2-antiplasmin, fibrin degradation product) were noted either after exercise or between the groups. Exercise in normal middle-aged men is associated with modest thrombin and plasmin activation.

Topics: Adult; Aged; Coronary Disease; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Humans; Male; Middle Aged; Peptide Fragments; Physical Exertion; Thrombin

Elevated levels of fibrinopeptide A, a marker of thrombin activity associated with acute myocardial infarction, have been found to decrease after administration of streptokinase when reperfusion occurs. In contrast, in patients without reperfusion and those with reocclusion after streptokinase therapy, fibrinopeptide A remains elevated. In the present study early serial measurements of fibrinopeptide A were used to further characterize this paradoxic increase in thrombin activity after streptokinase and to characterize its response to heparin. In 19 patients with acute myocardial infarction fibrinopeptide A was elevated to 82.3 +/- 43.5 ng/ml (mean +/- SE) before therapy. Thirty minutes after the initiation of streptokinase, fibrinopeptide A increased to 300.1 +/- 117.4 ng/ml (p less than 0.01), consistent with extensive thrombin activity. Fibrinopeptide A remained elevated until 15 minutes after a heparin bolus injection when levels decreased to 15% of the poststreptokinase value (49.2 +/- 13.3 ng/ml) (p less than 0.001). These data document a prompt paradoxic increase in thrombin activity after administration of streptokinase that may be responsible for failure of therapy in some patients.

Topics: Cardiomyopathies; Coronary Circulation; Coronary Disease; Coronary Thrombosis; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Humans; Streptokinase

Factors responsible for initial success or failure of coronary thrombolysis and persistent recanalization or early reocclusion have not been thoroughly elucidated. Both adequate initial clot lysis and preclusion of rethrombosis are required. Failure may reflect clot lysis followed immediately or somewhat later by rethrombosis. To determine whether differences in the intensity and persistence of the activation of thrombin are determinants of success or failure of recanalization, plasma fibrinopeptide A, a fibrinogen product liberated by thrombin, was serially assayed in 19 patients treated with intravenous streptokinase. In patients exhibiting recanalization (n = 9), plasma fibrinopeptide A decreased after administration of streptokinase but before administration of heparin. In patients without initially apparent recanalization, fibrinopeptide A increased, suggesting ongoing thrombosis, and subsequently decreased promptly after heparin. In patients with initial recanalization followed by overt reocclusion the pattern was different. Despite recanalization, fibrinopeptide A continued to rise markedly. Elevations persisted despite administration of heparin. Thus, inhibition of activation of thrombin is associated with successful recanalization. Conversely, persistent activation of thrombin may be a predisposing factor to both apparent initial failure of recanalization and overt early reocclusion.

Topics: Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Prognosis; Streptokinase; Thrombin

To determine whether coronary thrombosis in vivo is reflected by elevations in levels of fibrinopeptide A (FPA) in plasma, we sequentially characterized plasma FPA levels associated with evolving infarction in patients admitted to the cardiac care unit early after the onset of symptoms, in patients with transmural infarction admitted later, and in patients with nontransmural infarction. Studies were also performed in patients in whom the diagnosis of infarction was suspected but subsequently excluded. FPA values were significantly higher in patients with transmural infarction (42.3 +/- 11.2 ng/ml [mean +/- SEM], n = 53) compared with those in patients with nontransmural infarction (4.8 +/- 1.6 ng/ml, n = 17) or with those in patients in whom infarction was subsequently excluded as a diagnosis (3.5 +/- 0.6 ng/ml, n = 17, p less than .01 for both). Elevations in FPA level were greatest in patients with transmural infarction from whom samples were obtained soon after the onset of symptoms. Thus, in 39 patients from samples were obtained within 10 hr after the onset of symptoms, FPA levels were significantly higher than in 14 patients from whom samples were obtained initially more than 10 hr after the onset of symptoms (55.5 +/- 14.7 vs 4.9 +/- 1.4 ng/ml, p less than .01). In 30 of the 39 patients with evolving transmural infarction from whom samples were obtained within the first 10 hr after the onset of symptoms, the level of FPA was greater than 8 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Coronary Disease; Creatine Kinase; Female; Fibrinogen; Fibrinopeptide A; Humans; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Time Factors

Fibrinopeptide A (FPA) concentrations were measured in blood taken by direct cardiac puncture from 31 patients who had died suddenly of ischaemic heart disease (IHD) and from 8 patients who had died suddenly of other causes. Mean FPA concentration in the IHD group was five times higher than that in the non-IHD group. This difference was almost entirely due to the high FPA level in the IHD subjects with a history of the disease. The FPA difference between the IHD and non-IHD groups is unlikely to have been due to differences in methods of resuscitation. A possible interpretation of the findings is that thrombin production causes or aggravates the course of events leading to sudden IHD death, particularly in subjects with a past history of IHD.

Topics: Aged; Coronary Disease; Death, Sudden; Female; Fibrinogen; Fibrinopeptide A; Heart; Humans; Male; Massage; Middle Aged; Punctures; Resuscitation; Thrombin; Time Factors

The purpose of this study was to investigate the degree of platelet activation and thrombin generation in 40 patients with stable angina pectoris and in 20 patients with acute myocardial infarction (AMI) by determining the plasma beta thromboglobulin (BTG) and fibrinopeptide A (FPA) concentrations. In patients with angina pectoris increased platelet activation correlated with extensive coronary pathology; the activation, however, was not influenced by a previous myocardial infarction, use of oral anticoagulants, beta-blocking agents, or hyperlipidemia. The plasma beta thromboglobulin concentration predicted more accurately the extent of the coronary artery disease than the functional angina pectoris classification. Thrombin generation was within the normal range. In patients with acute myocardial infarction increased platelet activation and enhanced thrombin generation were found, which were not related to the infarct localization, infarct size, or the presence of complications. Consequently, in these patients determination of plasma beta thromboglobulin and fibrinopeptide A concentrations is useless for the diagnosis of venous thromboembolism.

Topics: Adult; Aged; Angina Pectoris; Beta-Globulins; beta-Thromboglobulin; Blood Platelets; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction; Myocardium; Thrombin; Thrombophlebitis

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.

Topics: Adult; Aged; Blood Platelets; Blood Proteins; Catecholamines; Coronary Disease; Exercise Test; Fibrin; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Physical Exertion; Renin; Thromboxane B2

In vivo platelet alpha-granule release and fibrin I formation were measured in 82 patients with ischemic heart disease by radioimmunoassay of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A. The presence and extent of coronary artery disease were determined by coronary arteriography, and the extent of left ventricular regional dysfunction was assessed by contrast left ventriculography. In patients with abnormal coronary arteriograms without previous myocardial infarction, mean levels of platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were not elevated. In patients in whom myocardial infarction had occurred more than 6 mo previously, platelet factor 4 (8.3 ng/ml; p less than 0.01) and beta-thromboglobulin (33.2 ng/ml; p less than 0.001) levels were significantly elevated, but fibrinopeptide A levels were normal. Levels of platelet factor 4 and beta-thromboglobulin were unrelated to the extent of coronary artery disease. In the patients with prior infarction, beta-thromboglobulin correlated directly with extent of left ventricular regional dysfunction (r = 0.53; p less than 0.01) and inversely with ejection fraction (r = -056; p less than 0.05). In a small group of patients with left ventricular aneurysm, mean fibrinopeptide A levels were also elevated. We interpret these findings as indicating that platelet release in patients with ischemic heart disease results from platelet reaction with previously infarcted myocardium rather than with the atherosclerotic coronary arteries.

Topics: Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Blood Coagulation Factors; Blood Platelets; Coronary Angiography; Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Heart Aneurysm; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Factor 4

In 98 patients with ischemic heart disease (IHD), independent of their clinical status (previous myocardial infarction, spontaneous angina or effort angina), a hypercoagulable state (indicated by significant elevation of fibrinopeptide A plasma level) and an increased platelet biologic activity were observed. Moreover, plasma fibrinopeptide A concentration and platelet aggregation were remarkably higher in patients with frequently occurring spontaneous clinical manifestations (active disease) than in IHD patients with relatively quiescent symptoms. Abnormalities of blood clotting and platelet changes were not significantly altered by the presence of severity of coronary angiographic fixed obstruction in IHD. Multiple regression analysis indicated that hypercoagulability and increased platelet biologic activity were not a consequence of differences in risk factor patterns in IHD patients compared to control subjects.

Topics: beta-Thromboglobulin; Blood Coagulation; Blood Platelets; Coronary Disease; Female; Fibrinogen; Fibrinopeptide A; Hemostasis; Humans; Male; Middle Aged; Platelet Aggregation; Risk; Thromboxane A2; Thromboxanes

Topics: Acute Disease; Angina Pectoris, Variant; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans