Simultaneous presence of tissue factor pathway inhibitor (TFPI) and low molecular weight heparin has a synergistic effect in different coagulation assays

Injection of heparin releases tissue factor pathway inhibitor (TFPI) to the blood and, after heparin neutralization, it has been recently demonstrated that the released TFPI has an anticoagulant activity. Using recombinant TFPI (rTFPI) we have investigated how the simultaneous presence of TFPI and low molecular weight heparin (LMW heparin) affects different coagulation assays. Coagulation was measured using the activated partial thromboplastin time, the prothrombin time and a dilute tissue factor assay. The anticoagulant activity of partly purified plasma TFPI (pTFPI) was much higher than that of TFPI. However, this high anticoagulant activity was unstable, so in order to investigate the effect of pTFPI and LMW heparin we used an inhibitory antibody towards TFPI and looked at the effect of removing TFPI from plasma. When both rTFPI and LMW heparin was added to plasma a synergistic effect was observed in all assays. In the tissue factor dependent coagulation assays, the effect of adding rTFPI or removing pTFPI was more pronounced in the presence of heparin. TFPI plays a significant role in assays where the coagulation time is prolonged for some reason. This may be caused by dilution of tissue factor, by the presence of heparin or by a defect in the coagulation cascade such as that seen in haemophilia.