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-fold in post-heparin plasma and thought to contribute significantly to the antithrombotic action of heparin. In the present study we investigated whether subcutaneous (s.c.) administration of a low molecular weight 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 continuous 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 72 h. A bolus injection of 5000 TCT UFH i.o. caused an 8-13-fold increase in plasma-free TEPI antigen (TFPI Ag), followed by a progressive decrease (81 +/- 4%, P<0.001) during the 72 h infusion with UFH. 4h after discontinuation of the infusion, basal free TFPI Ag and heparin-releasable TFPI were significantly decreased compared with the concentrations before the infusion (30 +/- 9% and 27 +/- 7%, respectively). In contrast, LMWH treatment did not reduce either basal or heparia-releasable TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statistically different between groups both in pre- (P<0.001) and post-heparin (P<0.0001) plasma. The differential effect of UFH and LMWH on intravascular pools of TFPI may contribute to the understanding of the apparent superior efficacy of LMWHs in the treatment of both arterial and venous thrombosis.