TFPI ANTIGEN LEVELS IN NORMAL HUMAN VOLUNTEERS AFTER INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATION OF UNFRACTIONATED HEPARIN AND A LOW-MOLECULAR-WEIGHT HEPARIN

Tissue factor pathway inhibitor (TFPI) is an important mediator of the in vivo anticoagulant/antithrombotic properties of unfractionated hep arin (UFH) and low molecular weight heparin (LMWH). The vascular pool of TFPI is released into the circulation after intravenous and subcuta neous administration of both UFH and LMWH. We have administered LMWH ( Ardeparin(R)) and UFH to normal human volunteers in a dose dependent m anner. Our results demonstrate that the TFPI antigen levels increase u pon the intravenous and subcutaneous administration of UFH and Ardepar in(R). Because of the better bioavailability of LMWH by the subcutaneo us route at equigravimetric dosages, Ardeparin(R) released more TFPI t han UFH. However, when given intravenously an identical release of TFP I from the vasculature has been observed. The plasma concentration of TFPI was increased 0.5 - 2 fold when UFH or Ardeparin(R) was administe red subcutaneously and was 3 fold higher when administered intravenous ly. This profound increase in TFPI antigen levels was dependent on the dosage of Ardeparin(R) administered. This release in TFPI correlates with prologation of the Heptest(R) clotting assay. However, it appears from this study that TFPI release precedes the elevation of the Hepte st(R) clotting time.