The Annals of Thoracic Surgery, Vol 58, 344-350, Copyright © 1994 by The Society of Thoracic Surgeons
Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass
A DeAnda Jr, SE Coutre, MR Moon, CM Vial, LC Griffin, VS Law, M Komeda, LL Leung and DC Miller
Department of Cardiovascular and Thoracic Surgery, Standford University School of Medicine, CA 94305-5247.
Heparin is normally used for anticoagulation during cardiopulmonary bypass
(CPB), but its use is contraindicated in patients with a history of
heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both.
Heparin therapy can also be ineffective due to heparin resistance. A
short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer)
may potentially serve as a substitute for heparin in these and other
clinical situations. We tested a novel thrombin aptamer in a canine CPB
pilot study to determine its anticoagulant efficacy, the resultant changes
in coagulation variables, and the aptamer's clearance mechanisms and
pharmacokinetics. Seven dogs were studied initially: Four received varied
doses of the aptamer (to establish the pharmacokinetic profile) and 3
received heparin. Subsequently, 4 other dogs underwent CPB, receiving a
constant infusion of the aptamer before CPB (to characterize the baseline
coagulation status), with partial CPB and hemodilution, during 60 minutes
of total CPB, and, finally, after a 2-hour recovery period. At a 0.5
mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion
from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p
= 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p =
0.017), and was even more prolonged during total CPB (> 1,500 seconds; p
< 0.001). This later increase in the activated clotting time paralleled
a rise in the plasma concentration of the thrombin aptamer during total
CPB, as determined by high-performance liquid chromatography.(ABSTRACT
TRUNCATED AT 250 WORDS)
