Effects of platelet glycoprotein IIb/IIIa inhibition with abciximab on thrombin generation and activity during percutaneous coronary intervention.
BACKGROUND
Antagonists of the platelet glycoprotein IIb/IIIa decrease acute ischemic complications after percutaneous coronary interventions (PCI). Abciximab (c7E3 Fab, ReoPro) has been reported to decrease thrombin generation in vitro. We investigated in vivo the effect of abciximab therapy on thrombin generation, thrombin activity, and the activated clotting time (ACT) during PCI.


METHODS
We studied 32 consecutive patients who underwent PCI for unstable coronary syndromes. Group I (n = 11) was treated with heparin plus aspirin, and group II (n = 21) was treated with heparin plus aspirin plus standard-dose abciximab, administered 5 minutes after the initial heparin bolus. Patients received a standardized heparin bolus at time 0, and arterial blood specimens for prothrombin fragment F1.2, fibrinopeptide A (FPA), and ACT were obtained from the guiding catheter at 5 minutes, 10 minutes (ACT only), 20 minutes, and at the end of the PCI. Standard-dose abciximab was administered in group II only. Each patient served as his or her own control, and the changes against the baseline were compared between the 2 groups.


RESULTS
There were no significant differences between the 2 groups regarding baseline characteristics, hematocrit, and platelet count. Group I patients had higher ACT and lower F1.2 and FPA compared with group II at baseline. Subsequent measurements demonstrated a gradual decrease in FPA and F1.2 in group II; the end of procedure versus baseline changes that occurred in F1.2 were significantly different compared with group I (decrease of 0.59 +/- 0.22 nmol/L in group II vs increase of 0.22 +/- 0.3 nmol/L in group I, P =.04), and a trend in the same direction was evident for FPA changes (decrease of 1.46 +/- 1.16 ng/mL in group II vs increase of 2.25 +/- 1.58 ng/mL in group I, P =.07). The ACT response to abciximab was variable, but a 6.3% increase (+20 sec) in ACT was documented 5 minutes after abciximab bolus in group II compared with the 3.4% decrease (-10 sec) observed in group I at the same time point (P =.1).


CONCLUSIONS
Addition of abciximab to heparin plus aspirin during PCI was associated with a significant decrease in thrombin generation and a borderline decrease in thrombin activity.
Dangas
G
G
Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA.
Marmur
J D
JD
King
T E
TE
De Leon
J
J
Sharma
S K
SK
Vidhun
R
R
Feldman
D
D
Stoynov
M Y
MY
Badimon
J J
JJ
Ambrose
J A
JA
D000077284:Abciximab; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D013917:Thrombin; D001241:Aspirin; D000077284:Abciximab