Comparison of Enoxaparin and Unfractionated Heparin on Thrombin Generation in Acute Coronary Syndromes without ST-Segment Elevation

Summary

Recent clinical trials have demonstrated a better ability of low-molecular-weight heparin, compared to unfractionated heparin, in reducing ischemic cardiac events in patients with acute coronary syndromes without ST-segment elevation. No data are available concerning the in-vivo comparison of enoxaparin and unfractionated heparin on thrombin generation in patients with unstable angina or non-Q-wave myocardial infarction. We measured the plasma levels of prothrombin fragment 1+2 (a marker of prothrombin activation) and thrombin/anti-thrombin complex (a marker of thrombin generation) in 45 patients with non ST-elevation acute coronary syndromes who were randomized to receive enoxaparin, 3000 IU anti-Xa as an i. v. bolus, followed by 70 IU anti-Xa/Kg every 8 h for 3 days (23 pts, Group 1) or a bolus of 100 IU/kg of unfractionated heparin followed by infusion for 3 days titrated to maintain the aPTT between 70 and 90 s (22 pts, Group 2). Plasma levels of prothrombin fragment 1+2 reduced significantly at 3^rd h of treatment in both groups (–42% in Group 1 and –45% in Group 2), reached the lowest plasma concentration at the 24^th h and exhibited a slight increase at the 72^nd h; no differences were observed between the two groups at any time points. Plasma thrombin/antithrombin complex levels had a similar behaviour: reduced markedly in both groups at the 3^rd h (–52% in Group 1 and –46% in Group 2), remained lower during the first two days and slightly rose at 72^nd h. No differences between the two groups in plasma levels of this marker were apparent during drug infusion. In Group 1 the aPTT did not show significant changes; in Group 2 the mean value of aPTT doubled the basal value at any time point of determination. Both enoxaparin and unfractionated heparin produced a marked and similar reduction of thrombin generation. Other unknown mechanisms might explain the different clinical effects of the two heparins.

Keywords

Acute coronary syndromes - low-molecular-weight heparin - thrombin generation

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