Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins

Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous and subcutaneous injections of heparins, and may thus contribute to the antithrombotic effect of heparins. A previous study suggested different abilities of various low molecular weight heparins (LMWH) to release endogenous TFPI, but the dose-response relationship was not determined. In the present study, the dose-response relationship for escalating doses of two LMWHs, dalteparin and enoxaparin, on the release of endogenous TFPI was investigated. Six healthy male participants were given 50, 100 and 200 U/kg dalteparin and 0.5, 1.0 and 2.0 mg/kg enoxaparin as a single subcutaneous injection. The study was a randomized, cross-over design with a 1-week wash-out period between each injection. Peak free TFPI antigen and TFPI activity were detected after only 1 h, whereas anti-activated factor X (anti-FXa) and anti-activated factor II (anti-FIIa) activities were detected after 2-6 h. Putative therapeutic equivalent doses of dalteparin and enoxaparin gave similar release of endogenous TFPI, but dissimilar effects on anti-FXa and anti-FIIa activities.