Effects of therapeutic doses of heparin on thrombolysis with tissue- type
plasminogen activator in rabbits
G Agnelli, C Pascucci, B Cosmi and GG Nenci
Istituto di Semeiotica Medica, Universita di Perugia, Italy.
The objective of the study was to evaluate the ability of heparin to
enhance the thrombolytic effect of recombinant tissue type plasminogen
activator (rt-PA) and to prevent thrombus growth during and after
thrombolysis with rt-PA. In the thrombolysis studies, three groups of
rabbits were infused with rt-PA at a dose of 0.5 mg, 1 mg, or 2.5 mg over 3
hours, respectively. Rabbits in each group were randomized to receive, in
addition to rt-PA, heparin, 20 or 60 antifactor Xa U/kg/h, or saline over 6
hours. The three doses of rt-PA produced the same extent of thrombolysis
both in the two groups treated with heparin (34% +/- 6%, 52% +/- 7%, and
79% +/- 8% in the lower dose group; 39% +/- 6%, 49% +/- 4%, and 81% +/- 6%
in the higher dose group) and in the group treated with saline (37% +/- 4%,
47% +/- 5%, and 84% +/- 7%). In the thrombus growth inhibition studies 0.5
mg of rt-PA was infused over 3 hours in each rabbit. In addition, the
rt-PA-treated rabbits were randomized to receive heparin, 20 or 60
antifactor Xa U/kg/h over 6 hours, or saline. At the end of infusion, no
statistically significant differences in thrombus growth were found in
three groups of rabbits (54.8 +/- 7.4 micrograms and 52.4 +/- 12.1
micrograms in the low and high dose of heparin groups, respectively, and
59.4 +/- 10.4 micrograms in the saline group). In different experiments
rabbits were randomized to receive heparin, 60 antifactor Xa U/kg/h, or
saline at the end of the rt-PA infusion. In these experiments heparin
inhibited thrombus growth more efficiently than saline (41.1 +/- 6.5
micrograms and 58.7 +/- 12.9 micrograms, respectively, P less than .05). In
vitro experiments confirmed that heparin is unable to prevent fibrin
accretion on the clots during lysis with rt-PA while both D-Phe-Pro-Arg-
CH2-Cl (PPACK) and hirudin are able to prevent the accretion of fibrin. We
conclude that the data obtained in these animal models do not support the
concomitant use of heparin and rt-PA. However, heparin could be used
successfully after rt-PA to inhibit thrombus growth.
Volume 76,
Issue 10,
pp. 2030-2036,
11/15/1990
Copyright © 1990 by The American Society of Hematology
