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 aft er intravenous and subcutaneous injections of heparins, and may thus contri bute to the antithrombotic effect of heparins. A previous study suggested d ifferent abilities of various low molecular weight heparins (LMWH) to relea se endogenous TFPI, but the dose-response relationship was not determined. In the present study, the dose-response relationship for escalating doses o f two LMWHs, dalteparin and enoxaparin, on the release of endogenous TFPI w as 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 subcutaneo us injection. The study was a randomized, cross-over design with a 1-week w ash-out period between each injection. Peak free TFPI antigen and TFPI acti vity were detected after only 1 h, whereas anti-activated factor X (anti-FX a) and anti-activated factor II (anti-FIIa) activities were detected after 2-6 h. Putative therapeutic equivalent doses of dalteparin and enoxaparin g ave similar release of endogenous TFPI, but dissimilar effects on anti-FXa and anti-FIIa activities. Blood Coagul Fibrinolysis 11:343-348 (C) 2000 Lip pincott Williams & Wilkins.