Extrinsic pathway inhibitor (EPI) and the post-heparin anticoagulant effect in tissue thromboplastin induced coagulation

Abstract

It is known that the anticoagulant effect of blood or plasma is greater when heparin is given in vivo than when added in similar heparin concentrations in vitro . In this study, we neutralized heparin in citrated blood with polybrene, and then triggered coagulation with dilute tissue thromboplastin (TTP) and CaCl 2. The clotting time was longer and the release of fibrinopeptide A (FPA) was retarded in the post injection samples compared to samples spiked with heparin in vitro . We have earlier reported that the extrinsic pathway inhibitor (EPI) is released to the blood after heparin injection. This was demonstrated here also for LMW heparin Enoxaparine both after intravenous and subcutaneous administration. Polyclonal blocking antibodies to EPI were added to blood or plasma heparinized in vivo or in vitro , and the direct heparin effect was neutralized with polybrene. When TTP and CaCl 2 now were added and clotting time and the release of FPA recorded, the postheparin effect was greatly reduced by the antibodies. Addition of EPI antibodies to post-heparin plasma samples from cancer patients caused a marked reduction in the thromboplastin clotting times. We conclude that the release of EPI to the blood contributes significantly to the anticoagulant effect of heparin ex vivo .