Effect of Abciximab on Prothrombin Activation and Thrombin Generation in Acute Coronary Syndromes Without ST-Segment Elevation

Abstract

Background — Abciximab is very effective in reducing major cardiac events in patients undergoing interventional procedures. Its antithrombotic effect is primarily attributable to the blocking of platelet glycoprotein IIb/IIIa receptors, but recent evidence suggests that it may have a direct antithrombin effect. No data are available concerning the effect of abciximab on the in vivo markers of prothrombin activation and thrombin generation in patients with acute coronary syndromes without ST elevation. Methods and Results — We measured the plasma levels of prothrombin fragment 1+2 (a marker of prothrombin activation) and the thrombin/antithrombin complex (a marker of thrombin generation) in 167 patients with acute coronary syndromes without ST elevation enrolled in the GUSTO IV ACS trial who were randomized to receive abciximab for 24 hours (52 patients), abciximab for 48 hours (59 patients), or placebo (56 patients) in addition to heparin. Blood samples were obtained at baseline (before any treatment), after 24 and 48 hours (before study drug discontinuation), and 1 month later. There was a significant increase in the plasma levels of prothrombin fragment 1+2 after 48 hours and after 1 month in all 3 groups, placebo ( P =0.0001), 24-hour abciximab ( P =0.0002), and 48-hour abciximab ( P =0.0001). The plasma thrombin/antithrombin complex levels were similar in the 3 groups at all time points and did not change during the study drug infusions. Conclusions — Abciximab does not decrease prothrombin activation and thrombin generation in patients with acute coronary syndromes without ST elevation not undergoing interventional procedures.