TY - JOUR
T1 - In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris
AU - Merlini, Piera Angelica
AU - Ardissino, Diego
AU - Rosenberg, Robert D.
AU - Colombi, Elisabetta
AU - Agricola, Pietro
AU - Oltrona, Luigi
AU - Ottani, Filippo
AU - Galvani, Marcello
AU - Bauer, Kenneth A.
AU - Bottasso, Bianca
AU - Bertocchi, Federico
AU - Mannucci, Pier Mannuccio
PY - 2000
Y1 - 2000
N2 - In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1 + 2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving eider recombinant hirudin (31 patients) or heparin (36 patients). Blood staples were obtained at baseline (before any treatment), after 3 to 5 days of study drag infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drag discontinuation 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 was statistically significant (P=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were sillily persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion 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 month (P=0.0001 for both hirudin and heparin). The fibrinopepfide A plasma levels 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 of patients have biochemical signs of increased thrombin generation.
AB - In patients with unstable angina, intravenous heparin reduces thrombin activity but does not influence thrombin generation. Recombinant hirudin, a direct thrombin inhibitor, may be more effective in inhibiting both thrombin generation and activity. We measured the plasma levels of prothrombin fragment 1 + 2 (a marker of thrombin generation) and fibrinopeptide A (a marker of thrombin activity) in 67 patients with unstable angina enrolled in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial who were receiving eider recombinant hirudin (31 patients) or heparin (36 patients). Blood staples were obtained at baseline (before any treatment), after 3 to 5 days of study drag infusion (immediately before discontinuation), and 1 month later. In the patients receiving recombinant hirudin, the prothrombin fragment 1+2 levels measured immediately before drag discontinuation 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 was statistically significant (P=0.032). One month later, the prothrombin fragment 1+2 levels in both groups were sillily persistently high and did not differ from baseline. Fibrinopeptide A plasma levels at the end of infusion 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 month (P=0.0001 for both hirudin and heparin). The fibrinopepfide A plasma levels 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 of patients have biochemical signs of increased thrombin generation.
KW - Hirudin
KW - Thrombin generation
KW - Unstable angina
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M3 - Article
C2 - 10978264
AN - SCOPUS:0033818487
VL - 20
SP - 2162
EP - 2166
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -