J. Harenberg et al., PROTAMINE NEUTRALIZATION OF THE RELEASE OF TISSUE FACTOR PATHWAY INHIBITOR ACTIVITY BY HEPARINS, Thrombosis and haemostasis, 70(6), 1993, pp. 942-945
The present study was designed to investigate the action of protamine
on the release of tissue factor pathway inhibitor (TFPI) activity by u
nfractionated (UF) and low molecular weight (LMW) heparin in healthy i
ndividuals. 5000 IU UF-heparin or 5000 IU LMW-heparin were given intra
venously followed by saline, 5000 U protamine chloride or 5000 U prota
mine sulfate intravenously after the 10 min blood sample. Then serial
blood samples for the measurement of TFPI activity and anti-factor Xa-
activity were taken, in order to detect a possible relation between t
he remaining anti-factor Xa activity after neutralization of LMW-hepar
in with protamine and TFPI activity and to establish whether or not a
rebound phenomenon of plasmatic TFPI occurs. There was no difference i
n the release and in the kinetics of TFPI by UF- and LMW-heparin with
subsequent administration of saline. After administration of protamine
TFPI activity decreased immediately and irreversibly to pretreatment
values. There were no differences between protamine chloride and prota
mine sulfate on the effect of TFPI induced by UF- or LMW-heparin. No r
ebound phenomenon of TFPI activity occurred. In contrast anti-factor X
a- activity, as measured by the chromogenic S2222-assay, issued the kn
own differences between UF- and LMW-heparin. The half-life of the aXa-
effect of LMW-heparin was twice as long as of UF-heparin. Protamine an
tagonized UF-heparin completely and about 60% of the anti-factor Xa ac
tivity of LMW-heparin, using chromogenic S2222-method. No differences
could be detected for protamine Chloride and sulfate form of protamine
. It is assumed that protamine displaces heparins from the binding sit
es of TFPI There were no differences between UF- and LMW-heparin. The
data indicate that the sustained antifactor Xa activity after antagoni
zation of LMW-heparins as well as heparin rebound phenomena are not me
diated by TFPI activity.