Plasma TFPI activity after intravenous injection of pentasaccharide (PS) and unfractionated heparin in rabbits.

Tissue Factor Pathway Inhibitor (TFPI), is known, to be released in plasma after injection of intravenous or subcutaneous injection of heparin or low molecular weight heparin (1,2). Addition of protamine or polybrene in plasma can neutralize anticoagulant effects of heparin in vitro but not completely ex vivo in patients treated with heparin (3). It was believed for many years that this post-heparin anticoagulant effect was due to another activity released by heparin. More recently it has been shown that post-heparin anticoagulant effect could be inhibited by anti-TFPI antibodies (4). Since we have shown in a previous work (5), that in healthy volunteers, pharmacokinetics of TFPI were more closely related to anti IIa activity than anti Xa activity we hypothesized that fragments with anti-IIa activity may be required for this release, possibly from vascular wall. In order to determine if a very low molecular weight glycosaminoglycan can release TFPI in plasma, in the present study, we compared plasma TFPI amidolytic activity after intravenous injection in rabbits of pentasaccharide (PS), a synthetic fragment of very low molecular weight and with a strong and exclusive anti Xa activity, and unfractionated heparin (UFH).