In vivo demonstration of an antithrombin effect of abciximab.
Abciximab prolonged the activated clotting time (ACT) in a post hoc analysis from the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications trial and an in vitro study has suggested an antithrombin effect of platelet glycoprotein IIb/IIIa inhibition. The purpose of this study was to evaluate the in vivo effects of abciximab on ACT and thrombin generation. In 46 patients undergoing coronary intervention, 24 received heparin and abciximab (group I), whereas 22 received heparin alone (group II). All received the same dose (70 U/kg) of heparin. Heparin was given after a baseline ACT, and in group I, abciximab was administered after the 5-minute ACT. Serial ACTs were recorded at baseline, 5, 10, 20, and every 30 minutes thereafter and at the procedure's end. No intervention including balloon angioplasty was performed until after the 20-minute ACT. The prothrombin fragment F1.2 (Nm/L) was measured at baseline, 20 minutes, and at the end of the procedure. Before (baseline) heparin and at 5 minutes, ACTs were similar. Abciximab prolonged ACT by a mean of 34 to 64 seconds starting with the 10-minute ACT and extending to the 50-minute ACT (all p <0.01 vs heparin alone). There was a progressive decrease in the F1.2 with abciximab, and baseline minus end F1.2 was 0.12 +/- 0.02 in group I versus 0.05 +/- 0.04 in group II, p <0.05. These data indicate a significant in vivo effect of abciximab plus heparin in increasing ACT and decreasing F1.2, results that are consistent with an effect on reducing thrombin generation.
Comprehensive Cardiovascular Center, Saint Vincents Hospital and Medical Center, 170 West 12th Street, New York, New York 10011, USA.
J A
JA
Ambrose
M
M
Hawkey
J J
JJ
Badimon
J
J
Coppola
J
J
Geagea
K P
KP
Rentrop
A
A
Domiguez
S
S
Duvvuri
T
T
Elmquist
J
J
Arias
R
R
Doss
G
G
Dangas
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000097:blood; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000032:analysis; D014914:Whole Blood Coagulation Time
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D000991:Antithrombins; D007140:Immunoglobulin Fab Fragments; D011516:Prothrombin; D006493:Heparin; D000077284:Abciximab