fibrin and Angina--Unstable

In acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity.. The Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST-elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours.. The median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4-7.8 ng/L, P <.001; 4.4-8.7 mg/L, P <.001; 3.3-3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups.. In non-ST-elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.

Topics: Abciximab; Aged; Angina, Unstable; Antibodies, Monoclonal; Anticoagulants; Biomarkers; Blood Coagulation; Blood Coagulation Factors; C-Reactive Protein; Dalteparin; Double-Blind Method; Electrocardiography; Female; Fibrin; Fibrinolysis; Humans; Immunoglobulin Fab Fragments; Inflammation; Interleukin-6; Male; Middle Aged; Platelet Aggregation Inhibitors

Diagnosis of acute coronary syndromes (ACS) is a major challenge for emergency physicians. Because soluble fibrin (sF) has been suggested as a potential early marker of impending myocardial ischemia, we were interested whether a sF bedside test could help in early identification of patients with ACS in the emergency department.. We evaluated plasma coagulation markers, including a newly developed sF bedside test, prothrombin fragment (F(1+2)), sF, and D-dimer, in a cross-sectional trial with 184 patients suggestive of ACS.. Whereas 76% (13 of 17) of patients with unstable angina pectoris (UAP) had a positive sF bedside test, only 10 of 33 patients (30%) with non-ST-segment-elevation myocardial infarction and 10 of 44 patients (23%) with ST-elevation myocardial infarction tested positive. Three percent of controls (1 of 33) and 11% of patients (6 of 57) with preexisting stable angina had a positive sF bedside test (P <0.001 for noncardiac chest pain vs ACS), yielding an overall specificity of 92% and a sensitivity of 35%. The sensitivity of the established coagulation markers was significantly less to detect ACS (11% for F(1+2), 20% for thrombus precursor protein, and 18% for D-dimer; P <0.02 vs sF bedside test). The sF bedside test presented the earliest objective indicator of impending myocardial damage in the majority (10 of 13) of ACS patients with a normal or nondiagnostic electrocardiogram (ECG).. A sF bedside test offers a specific tool for early identification of patients with ACS in an emergency department setting, although its sensitivity seems sufficient only for the early identification of patients with UAP. A sF bedside test could be useful, particularly in UAP patients with a nondiagnostic ECG.

Topics: Acute Disease; Angina, Unstable; Biomarkers; Blood Coagulation Tests; Emergency Medical Services; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Point-of-Care Systems; Sensitivity and Specificity

In the current study, we investigated molecular markers of coagulation activity, ie, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer, and their relation to death, myocardial infarction, and refractory angina during and after anticoagulant treatment in unstable coronary artery disease. Patients with unstable coronary artery disease (N=320) were randomized to a 72-hour infusion with either inogatran, a low-molecular-mass direct thrombin inhibitor, or unfractionated heparin. During the 30-day follow-up, a 40% lower event rate was seen in patients with high compared with low baseline levels of TAT or SF. High baseline levels of coagulation activity were correlated with a larger decrease during treatment. Patients with decreased compared with raised F1+2 or TAT levels after 6 hours of treatment had a 50% lower event rate at 30 days (F1+2, P=0.04; TAT, P=0.02). At the cessation of antithrombin treatment, there was a clustering of cardiac events that tended to be related to a rise in the levels of TAT and the other markers. During long-term follow-up (median, 29 months), there was a relation between higher baseline levels of D-dimer (P=0.003) and increased mortality. High baseline levels of molecular markers of coagulation activity might identify patients with a thrombotic condition (as the major cause of instability) who are good responders to anticoagulant therapy, with a larger decrease in coagulation activity during treatment and a decreased risk of ischemic events. However, this early benefit is lost during long-term follow-up when high baseline levels of coagulation activity are associated with a raised risk of early reactivation and increased mortality.

Topics: Adult; Aged; Angina, Unstable; Anticoagulants; Antithrombin III; Antithrombins; Biomarkers; Blood Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Glycine; Heparin; Humans; Kinetics; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Peptide Hydrolases; Piperidines; Prothrombin; Random Allocation; Treatment Outcome

This study evaluated a novel specific thrombin inhibitor, inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease.. In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked.. The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.

Topics: Aged; Angina, Unstable; Antithrombins; Biomarkers; Electrocardiography; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinolytic Agents; Follow-Up Studies; Glycine; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Partial Thromboplastin Time; Piperidines; Prothrombin; Thrombin; Treatment Outcome

Of 35 acetylsalicylic acid (ASA)-treated patients undergoing coronary artery bypass surgery, 10 received a high dose of aprotinin (mean 5.2 x 10(6) KIU) during cardiopulmonary bypass (CPB); in 15 cases low-dose aprotinin (2 x 10(6) KIU) was added to the CPB priming solution, and 10 patients made up a control group without aprotinin. Median total blood loss was 52% less in aprotinin-treated patients, irrespective of dose, than in the controls. Fibrin-D dimer levels remained low in patients treated with high-dose aprotinin, but increased significantly in the control group. Platelet adhesion and platelet adenosine triphosphate secretion were reduced after CPB in all patients. Whole-blood aggregation after bypass was enhanced in aprotinin-treated patients. Aprotinin inhibited fibrinolysis and seemingly preserved platelet function despite ASA treatment. In view of the possible risks and relatively high cost of aprotinin, use of a high dose seems unnecessary, since a low dose was equally effective in reducing blood loss in ASA-treated patients.

Topics: Adenosine Triphosphate; Adult; Aged; Angina, Unstable; Aprotinin; Aspirin; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Confidence Intervals; Dose-Response Relationship, Drug; Female; Fibrin; Fibrinolytic Agents; Hemostatics; Humans; Injections, Intravenous; Male; Middle Aged; Platelet Adhesiveness; Platelet Count; Preoperative Care; Reference Values; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Angioscopy; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Infarction

Identify whether the plasma concentration of Lp(a), apo(a) size or a greater affinity for fibrin predict the likelihood of cardiac death, non-fatal myocardial infarction, unstable angina, the need for additional revascularization, and stroke (MACCE).. We analyzed the clinical prognosis of 68 patients with coronary artery disease included in a case-controlled study which evaluated Lp(a) concentration, apo(a) size, and Lp(a) fibrin-binding. Cohort was conducted over a median of 8 years. We used Kaplan-Meier survival tables to evaluate cardiovascular and cerebrovascular events in the follow-up period.. Apo(a) isoforms of small size are predictors of MACCE. We find an association between Lp(a) concentration and apo(a) fibrin-binding with major adverse cardiovascular and cerebrovascular events, although without statistically significant results.. Small-sized apo(a) isoforms are an independent risk factor for MACCE in patients with coronary artery disease in follow-up. Lp(a) plasma concentration and apo(a) fibrin-binding were associated, although not significant.

Topics: Adult; Angina, Unstable; Apolipoproteins A; Coronary Artery Disease; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Humans; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Phenotype; Prognosis; Protein Binding; Stroke

In a majority of instances, both unstable angina and acute myocardial infarction occur secondary to plaque disruption and thrombus formation. Although the pathogenetic substrates are similar the clinical presentations are quite different. It is hypothesized in this editorial review that the amount of acute thrombus formation and specifically fibrin deposition is greater in myocardial infarction than in unstable angina. Both angiographic studies and studies analyzing the response to thrombolytic agents suggest more thrombus in myocardial infarction than in unstable angina. These data have recently been substantiated by angioscopic observations in these acute syndromes suggesting that more platelet-rich (whitish) thrombus occurs in unstable angina and more red thrombus in myocardial infarction. The red thrombus presumably would be more responsive to thrombolytic agents. Furthermore, it is proposed that these differences between syndromes in acute thrombus formation can be explained by the interplay of vessel wall injury, coagulation variables or stasis of blood flow occurring at or after the time of presentation. Therefore, acute myocardial infarction is associated with occlusive, fibrin-rich thrombus, whereas in unstable angina, the thrombus is nonocclusive, mural and possibly more platelet-rich. However, the clinical syndrome that ultimately develops after plaque disruption is dependent not only on the amount of acute thrombus formation but on the net result of all factors that influence the balance between coronary blood supply and myocardial oxygen demand.

Topics: Angina, Unstable; Blood Platelets; Coronary Angiography; Coronary Thrombosis; Endoscopy; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Myocardial Infarction; Plasminogen Inactivators; Thrombolytic Therapy