The effect of heparin on fibrinolytic activity and platelet
function in vivo.
Upchurch, Gilbert R., C. Robert Valeri, Shukri F. Khuri, Michael J.
Rohrer, George N. Welch, Holly Macgregor, Gina Ragno, Stephanie
Francis, Louis J. Rodino, Alan D. Michelson, and Joseph Loscalzo.
The Naval Blood Research Laboratory, Boston University School of
Medicine, Boston, MA: the Department of Pediatrics and Division of
Vascular Surgery, University of Massachusetts Medical School,
Worcester, MA; and the Departments of Surgery, Brigham and Women's
Hospital and Brockton/West Roxbury Veterans Administration Medical
Center, Boston, Massachusetts 02118
APStracts 3:0025H, 1996.
Heparin, a polyanionic glycosaminoglycan, is used routinely prior to
the induction of cardiopulmonary bypass. Earlier observations in our
laboratory suggested that the postoperative bleeding which occurs,
despite neutralization of heparin with protamine, is secondary to
hypothermia and dilutional anemia during bypass. An additional,
potential mechanism for excessive bleeding following cardiopulmonary
bypass is that heparin activates the fibrinolytic system, which may,
in turn, adversely affect hemostasis. To understand better the
effects of heparin administration on the fibrinolytic system in vivo,
we simulated the anticoagulant regimen of cardiopulmonary bypass by
administering increasing doses of intravenous heparin to five adult
baboons over 60 minutes. We measured fibrinolytic parameters serially
following heparinization, and demonstrated that heparin induces
activation of the fibrinolytic system. We showed that the
fibrinolytic system was activated in vivo as evidenced by an increase
in plasmin activity and immunoreactive plasmin light chain, as well
as an increase in immunoreactive fibrinogen fragment E in vitro.
These results demonstrate that the fibrinolytic system is activated
in vivo by the administration of heparin during cardiopulmonary
bypass. These data suggest that, despite administration of a
neutralizing agent such as protamine, heparin may contribute to
postoperative bleeding complications following cardiopulmonary bypass
surgery owing principally to its longer-lived effects on the
fibrinolytic system.
Received 1 September 1995; accepted in final form 8 August 1995.
APS Manuscript Number H829-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96