Efficacy of unfractionated heparin, low molecular weight heparin and both combined for releasing total and free tissue factor pathway inhibitor

Unfractionated heparin (UFH) exerts its anticoagulant properties by increas ing the inactivation of thrombin and activated factor X by antithrombin III . Apart from this main action release of tissue factor pathway inhibitor (T FPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected sub cutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix do se (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH) , (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) a nd (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn b efore and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the con centration of total and free TFPI. Total TFPI increased in the 1st hour aft er LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74. 5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng /ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI co mpared with FixUFH at 2, 4 and 6 h (p < 0.01). We concluded that at compara ble therapeutic doses, subcutaneous UFHvar released more free TFPI than LMW H and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.