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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1059.)
© 2001 American Heart Association, Inc.

Thrombosis

Coagulation Activity and Clinical Outcome in Unstable Coronary Artery Disease

J. Oldgren; R. Linder; L. Grip; A. Siegbahn; L. Wallentin

From the Department of Medical Sciences, Cardiology (J.O., L.W.) and Clinical Chemistry (A.S.), University Hospital, Uppsala; the Department of Cardiology (R.L.), Karolinska Hospital, Stockholm; and the Department of Cardiology (L.G.), Sahlgrenska University Hospital, Gothenburg, Sweden.

Correspondence to Jonas Oldgren, MD, Department of Medical Sciences, Cardiology, Uppsala University Hospital, S-751 85 Uppsala, Sweden. E-mail Jonas.Oldgren{at}medsci.uu.se

Abstract—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.

Key Words: unstable angina • myocardial infarction • coagulation • thrombin inhibition