PROTAMINE NEUTRALIZATION OF THE RELEASE OF TISSUE FACTOR PATHWAY INHIBITOR ACTIVITY BY HEPARINS

Citation
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
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiac & Cardiovascular System
Journal title
ISSN journal
0340-6245
Volume
70
Issue
6
Year of publication
1993
Pages
942 - 945
Database
ISI
SICI code
0340-6245(1993)70:6<942:PNOTRO>2.0.ZU;2-M
Abstract
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.