DIFFERENTIAL EFFECT OF UNFRACTIONATED HEPARIN AND LOW-MOLECULAR-WEIGHT HEPARIN ON INTRAVASCULAR TISSUE FACTOR PATHWAY INHIBITOR - EVIDENCE FOR A DIFFERENCE IN ANTITHROMBOTIC ACTION

Tissue factor pathway inhibitor (TEPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation, which is increased several-fol d in post-heparin plasma and thought to contribute significantly to th e antithrombotic action of heparin. In the present study we investigat ed whether subcutaneous (s.c.) administration of a low molecular weigh t heparin (LMWH), enoxaparin, had a different effect on intravascular pools of TFPI compared with continuous i.o. infusion of unfractionated heparin (UFH). 18 healthy male volunteers were randomly assigned to c ontinuous i.v. infusion with UFH (initially 450 U/kg/24h, n=6) or to s .c. treatment with LMWH once daily (enoxaparin, 1.5 mg/kg, n=12) for 7 2 h. A bolus injection of 5000 TCT UFH i.o. caused an 8-13-fold increa se in plasma-free TEPI antigen (TFPI Ag), followed by a progressive de crease (81 +/- 4%, P<0.001) during the 72 h infusion with UFH. 4h afte r discontinuation of the infusion, basal free TFPI Ag and heparin-rele asable TFPI were significantly decreased compared with the concentrati ons before the infusion (30 +/- 9% and 27 +/- 7%, respectively). In co ntrast, LMWH treatment did not reduce either basal or heparia-releasab le TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statist ically different between groups both in pre- (P<0.001) and post-hepari n (P<0.0001) plasma. The differential effect of UFH and LMWH on intrav ascular pools of TFPI may contribute to the understanding of the appar ent superior efficacy of LMWHs in the treatment of both arterial and v enous thrombosis.