Effects of low-molecular-weight heparin treatment on fibrinolytic markers in unstable coronary artery disease

Abstract

Objectives: Low-molecular-weight heparins (LMWHs) efficiently reduce the coagulant activity, but their influence on the fibrinolytic system and fibrin turnover is not fully elucidated. We therefore determined markers offibrinolytic activity, fibrin turnover and inflammation in LMWH treated patients with acute coronary artery disease.Design: Double-blind placebo controlled clinical trial.Setting: Consecutive patients admitted at two centers.Subjects: Individuals with unstable angina or non-Q-wave MI (n= 87).Interventions: Randomized to placebo-controlled subcutaneous dalteparin treatment, 120 IU/kg bw twice daily for 5–8 days and 7500IU once daily over the next 35–45 days.Main outcome measures: Markers of fibrinolytic activity, i.e. tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen anti-plasmin (PAP) complex, and D-dimer determined at inclusion, after 2, 5 and 40–50 days. C-reactive protein (CRP), fibrinogen and prothrombin fragment 1+2 (F1+2) were determined at inclusion.Results: At inclusion there were positive correlations between fibrinogen, CRP and D-dimer levels. During LMWH treatment there was a marked increase in t-PA antigen concentration, a rise in PAI-1 activity and a slight decrease in PAP-complex levels. The LMWH administration was also associated with a long-lasting decrease in the D-dimer concentrations. In the placebo group there was a slight and transient increase in all the evaluated markers of fibrinolytic activity and fibrin turnover.Conclusion: In unstable CAD increased inflammatory activity is associated with increased thrombin generation and fibrin turnover. During LMWH treatment there is a sustained reduction in fibrin turnover and no rise in plasmin generation despite an increase in t-PA level.