In vitro effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time.
BACKGROUND
In the evaluation of 7E3 for the Prevention of Ischemic Complications study (EPIC), the activated coagulation (clotting) times (ACTs) were longer in heparinized patients treated with c7E3 Fab than in those treated with placebo. The present study was designed to further investigate this observation by assessing whether the in vitro addition of c7E3 Fab to blood would affect the ACT.


RESULTS
Native or heparinized blood obtained from normal volunteers was preincubated with antibodies c7E3 Fab (anti-GPIIb/IIIa and anti-alpha v beta 3), 10E5 (anti-GPIIb/IIIa), or LM609 (anti-alpha v beta 3). The ACTs of the heparinized, but not native samples were significantly prolonged by the addition of c7E3 Fab and 10E5 but not LM609, indicating that the prolongation was due to GPIIb/IIIa blockade. The addition of c7E3 Fab also significantly prolonged the ACTs of blood anticoagulated with the direct thrombin inhibitors hirudin and D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone, indicating that the effect of c7E3 Fab was not exclusively related to decreased release of PF4, a heparin-neutralizing factor, from platelets.


CONCLUSIONS
These data support the conclusion that the prolongation of the ACT in patients in EPIC was due to c7E3 Fab blockade of GPIIb/IIIa receptors. This raises the possibility that in vivo c7E3 Fab functions not only as an antiplatelet agent but also as an anticoagulant; direct in vivo data will, however, be required for assessment of this possibility.
Ammar
T
T
Department of Anesthesiology, Mount Sinai Medical Center, New York, NY 10029, USA.
Scudder
L E
LE
Coller
B S
BS
D000077284:Abciximab; D000328:Adult; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology; D002417:Cattle / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000032:analysis / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007422:Intestines / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D013552:Swine; D014914:Whole Blood Coagulation Time
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D000991:Antithrombins; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C032193:glycoprotein receptor GPIb-IX; D006493:Heparin; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D000077284:Abciximab