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).

Lack of Correlation Between Activation of Hemostatic Mechanism and Inflammation in Unstable Angina Pectoris.

In the acute phase of unstable angina, activation of the hemostatic mechanism is demonstrated by an increase in the plasma levels of markers of thrombin generation (prothrombin fragment 1+2) and thrombin activity (fibrinopeptide A). Increased concentrations of plasma C-reactive protein, an acute-phase reactant, have also been reported in patients with unstable angina. However, whether there is a correlation between the activation of the hemostatic mechanism and the acute-phase reaction of inflammation remains unclear.

Tissue factor in human coronary atherosclerotic plaques.

The rupture or fissuring of a coronary atherosclerotic plaque and subsequent thrombosis is considered the key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque disruption frequently occurs during the evolution of atherosclerosis, only a minority of ruptured plaques develop thrombosis. The content and procoagulant activity of tissue factor in human coronary atherosclerotic plaques varies widely, and different studies confirm that it is higher in the plaques extracted from patients with unstable angina, myocardial infarction or histologic/angiographic evidence of coronary thrombosis than in those taken from patients with stable angina or uncomplicated coronary lesions.

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

Background: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase.

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.

Antithrombotic therapy of unstable angina and non-Q-wave myocardial infarction.

Unstable angina and non-Q-wave myocardial infarction still represent an unsolved problem for clinicians, owing to their unpredictable evolution and high incidence of coronary events in the follow-up. Traditional antithrombotic agents, unfractionated heparin and aspirin, have been proved to be highly effective, but show some important limitations. New potent antithrombotic therapy have been studied to improve their efficacy, with encouraging results.

Prognostic value of the admission electrocardiogram in acute coronary syndromes.

Context: The presence of ischemic changes on electrocardiogram (ECG) correlates with poorer outcomes in patients with acute chest pain.

Objective: To determine the prognostic value of various ECG presentations of acute myocardial ischemia.

Design: Retrospective analysis of the presenting ECGs of patients enrolled in Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb).

Death and nonfatal reinfarction within the first 24 hours after presentation with an acute coronary syndrome: experience from GUSTO-IIb. Global Utilization of Strategies for Total Occlusion.

Background: A large proportion of deaths among patients with myocardial infarction occurs within the first 24 hours after presentation. It is not clear whether this phenomenon is also true of patients without ST-segment elevation who may or may not have infarction at the time of presentation. Thrombin activity may also be greatest during the first 24 hours after plaque rupture.

Adjunctive stent implantation following directional coronary atherectomy in patients with coronary artery disease.

Objectives: This prospective case-control study evaluated the acute and long-term results of stent implantation preceded by debulking of the plaque by means of directional coronary atherectomy.

Background: In comparison with balloon angioplasty, intracoronary stenting produces a larger luminal diameter, maintains artery patency and reduces the incidence of restenosis. Optimal stent deployment is a pivotal factor for achieving the best results, but the bulk of the atherosclerotic plaque opposes stent expansion and may limit the success of the procedure.

[Coronary lesion with an aneurysm: their correction via angioplasty and the implantation of a coated stent].

We describe the good angiographic results obtained using a new polymeric prosthesis combining a stent with expandable polytetrafluoroethylene (PTFE) graft material in the treatment of proximal left descending coronary artery stenosis complicated by the presence of a coronary aneurysm.

Selection of drug therapy in stable angina pectoris.

Drug therapy in stable angina has two aims: the prevention of major cardiac events (such as unstable angina, myocardial infarction, or death) and the control of chest pain and transient myocardial ischemia. Given the low incidence of major cardiac events in patients with stable angina, primary preventive studies are scarce because they require a large sample size and long-term follow-up. Thus far, only aspirin and some lipid-lowering agents have been shown to be effective for this purpose.

The heterozygous 20210 G/A prothrombin genotype is associated with early venous thrombosis in inherited thrombophilias and is not increased in frequency in artery disease.

A genetic variation in the 3'-untranslated region of the prothrombin mRNA (20210 G/A) has recently been reported to be associated with elevated plasma prothrombin levels and with an increased incidence of venous thrombosis. We determined the frequency of this mutation, the detection of which was improved by allele-specific amplification of exon 14 and by denaturing gradients (denaturing gradient gel electrophoresis), in cohorts of patients affected by venous thrombosis (n = 132) or by coronary or cerebrovascular diseases (n = 195) and in normal subjects from various populations. An overlapping frequency of the heterozygous genotype (4%) was found in normal subjects from Italy and Cyprus, and no carrier was detected in 40 subjects of Indian or Somali origin.

C-reactive protein elevation and early outcome in patients with unstable angina pectoris.

C-reactive protein, a reactant of the acute phase of inflammation, has been shown to be increased in patients with unstable angina. Moreover, it has recently been found that increased C-reactive protein is associated with a poor outcome during hospitalization in selected patients with severe unstable angina. The aim of this study was to investigate the prognostic value of C-reactive protein elevation in a large population with unstable angina.

Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes.

Intravenous heparin, a fundamental therapy in the treatment of patients with acute coronary syndromes, acts by inhibiting thrombin and activated factors X, IX, XI, and XII. It has also been demonstrated that heparin reduces plasma fibrinopeptide A, a marker of thrombin activity, but it is unknown whether it decreases prothrombin fragment 1+2, an indirect marker of thrombin generation. We measured the plasma levels of prothrombin fragment 1+2, fibrinopeptide A, and antithrombin III in 64 consecutive patients with unstable angina or myocardial infarction receiving intravenous heparin.

Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.

Objectives: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris.

Background: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina.

Tissue-factor antigen and activity in human coronary atherosclerotic plaques.

Background: Coronary atherosclerotic-plaque thrombosis is a key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develop thromboses.

Methods: Tissue-factor antigen and activity were measured in atherectomy samples from 50 consecutive patients with coronary artery disease (stable angina n = 19, unstable angina n = 24, and myocardial infarction n = 7).

Prolonged streptokinase infusion in patients with unstable angina: results of a randomized, placebo-controlled clinical trial.

Background: The purpose of this study was to assess the efficacy both of prolonged (48 h) and of short-duration (1 h) administrations of streptokinase in patients with unstable angina. In unstable angina, thrombosis is a dynamic process that waxes and wanes for hours and even days. The majority of previous studies have investigated the efficacy of short-duration thrombolytic regimens.

Factor V (Arg 506-->Gln) mutation in young survivors of myocardial infarction.

Many young patients with venous thromboembolic disease are partially resistant to the anticoagulant action of activated protein C as a result of factor V (Arg 506 --> Gln) mutation. The frequency of this mutation in young patients with arterial thrombotic diseases, such as myocardial infarction, is less well established. We studied 100 young patients with myocardial infarction and 100 age- and sex-matched controls.

Thrombin activity and early outcome in unstable angina pectoris.

Background: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome.

Methods And Results: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed.

Activation of the hemostatic mechanism during thrombolysis in patients with unstable angina pectoris.

In patients with myocardial infarction, thrombolytic therapy induces a paradoxical activation of the hemostatic mechanism. In patients with unstable angina, the effect of thrombolysis on the coagulation cascade is unknown. We prospectively measured the plasma concentrations of prothrombin fragment 1 + 2 and fibrinopeptide A in consecutive patients with unstable angina randomized to receive placebo alone (n = 23), streptokinase 1,500,000 IU over 1 hour followed by a 48-hour placebo infusion (n = 21), or streptokinase 250,000 over 1 hour followed by a continuous infusion of 100,000 IU per hour over 48 hours (n = 20).