In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris

In patients with unstable angina, intravenous heparin reduces thrombin acti vity but does not influence thrombin generation. Recombinant hirudin, a dir ect thrombin inhibitor, may be more effective in inhibiting both thrombin g eneration and activity. We measured the plasma levels of prothrombin fragme nt 1 + 2 (a marker of thrombin generation) and,fibrinopeptide A (a marker o f thrombin activity) in 67 patients with unstable angina enrolled in the GU STO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving either recombinant hirudin (31 patients) or heparin (36 patients). Blood samples were obtained at baseline (before any treatment), after 3 to 5 days of study drug infusion (immediately before discontinuati on), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1 + 2 levels measured immediately before drug disconti nuation were significantly lower than at baseline (P=0.0014), whereas they had not changed in the patients receiving heparin; at this time point, the difference between patients receiving hirudin and those receiving heparin w as statistically significant (P=0.032), One month later, the prothrombin fr agment 1 + 2 levels in both groups were similarly persistently high and did not differ from:baseline. Fibrinopeptide A plasma levels at the end of inf usion were significantly lower than at baseline in both treatment groups (P =0.0005 for hirudin and P=0.042 for heparin) and remained lower after 1 mon th (P=0.0001 for both hirudin and heparin). The fibrinopeptide A plasma lev els were not different between patients treated with hirudin versus heparin at baseline, at the end of infusion, and after 1 month. Thus, in patients with unstable angina, in vivo thrombin generation and activity are reduced during intravenous infusion of recombinant hirudin. However, the inhibition of thrombin generation is not sustained, and after 1 month, the majority o f patients have biochemical signs of increased thrombin generation.