Thrombin Activity and Early Outcome in Unstable Angina Pectoris

Ardissino, Diego; Merlini, Piera Angelica; Gamba, G; Barberis, Peter; Demicheli, Gloria; Testa, Sophie; Colombi, Elisabetta; Poli, Arnaldo; Fetiveau, Raffaela; Montemartini, C

doi:10.1161/01.cir.93.9.1634

Cited by 75 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The decrease in thrombin-antithrombin during infusion, observed in both groups, may well be interpreted as a reduction in thrombin generation, but according to the explanation, a comparison between inogatran and heparin on the basis of this marker is questionable. Fibrinopeptide A, which reflects thrombin activity, has been analysed in similar studies and may, despite the risk of venipuncture-procedure related variations, allow a more reliable comparison between heparin and a direct thrombin inhibitor [19,[27][28][29][30][31] . Markers for thrombin activity have been shown to increase in patients with unstable coronary artery disease in comparison to control patients or healthy individuals [31][32][33] .…”

Section: Discussionmentioning

confidence: 99%

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease

Linder

Oldgren²,

Egberg³

et al. 1999

European Heart Journal

View full text Add to dashboard Cite

Aim 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. Methods and ResultsIn 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. ConclusionThe 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. (Eur Heart J 1999; 20: 506-518)

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease

Linder

Oldgren²,

Egberg³

et al. 1999

European Heart Journal

View full text Add to dashboard Cite

show abstract

“…1,2 Owing to a multiplier effect in the coagulation cascade, relatively low concentrations of factor Xa lead to the downstream production of large quantities of thrombin, with ultimate deposition of fibrin strands, as well as activation of platelets. 3,4 Clinical studies 5 suggest that patients with an acute coronary syndrome who demonstrate biochemical evidence of activation of the coagulation cascade are at increased risk of clinical events. Also, as reported by Merlini et al, 6 there is persistent activation of the coagulation cascade for several weeks to months after the index event, which has led investigators to design antithrombotic treatments that can be administered on a long-term basis.…”

mentioning

confidence: 99%

Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non–Q-Wave Myocardial Infarction

et al. 1999

View full text Add to dashboard Cite

MD; for the TIMI 11B Investigators* Background-Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non-Q-wave myocardial infarction (UA/NQMI). Methods and Results-Patients (nϭ3910) with UA/NQMI were randomized to intravenous UFH for Ն3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing Ͻ65 kg and 60 mg for those weighing Ն65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; Pϭ0.048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00; Pϭ0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin (Pϭ0.021). Conclusions-Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage. (Circulation. 1999;100:1593-1601.)

show abstract

“…Activation of the coagulation and fibrinolytic systems, as demonstrated by elevated markers of thrombin generation, thrombin activity and fibrin turnover, have been demonstrated in the acute phase of unstable CAD and are associated with an adverse outcome (62)(63)(64). Also reduced fibrinolytic capacity has been associated with an increased risk of coronary events in community based populations (65) as well as in unstable angina (66).…”

Section: Markers Of Coagulation and Fibrinolysis Activitymentioning

confidence: 99%

Coagulation, inflammation and myocardial dysfunction in unstable coronary artery disease and the influence of glycoprotein IIb/IIIa inhibition and low molecular weight heparin

James

2004

Upsala Journal of Medical Sciences

View full text Add to dashboard Cite

Thrombin Activity and Early Outcome in Unstable Angina Pectoris

Abstract: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Cited by 75 publications

References 25 publications

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease

Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non–Q-Wave Myocardial Infarction

Coagulation, inflammation and myocardial dysfunction in unstable coronary artery disease and the influence of glycoprotein IIb/IIIa inhibition and low molecular weight heparin

Contact Info

Product

Resources

About