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 heparin (UFH) and low molecular weight heparin (LMWH). The vascular pool of TFPI is released into the circulation after intravenous and subcutaneous administration of both UFH and LMWH. We have administered LMWH (Ardeparin(R)) and UFH to normal human volunteers in a dose dependent manner. Our results demonstrate that the TFPI antigen levels increase upon the intravenous and subcutaneous administration of UFH and Ardeparin(R). Because of the better bioavailability of LMWH by the subcutaneous route at equigravimetric dosages, Ardeparin(R) released more TFPI than UFH. However, when given intravenously an identical release of TFPI from the vasculature has been observed. The plasma concentration of TFPI was increased 0.5 - 2 fold when UFH or Ardeparin(R) was administered subcutaneously and was 3 fold higher when administered intravenously. 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 Heptest(R) clotting time.