ROLE OF TISSUE FACTOR PATHWAY INHIBITOR IN POST SURGICAL DEEP VENOUS THROMBOSIS (DVT) PROPHYLAXIS IN PATIENTS TREATED WITH LOW-MOLECULAR-WEIGHT HEPARIN

Low molecular weight heparins (LMWHs) are now considered to be the dru gs of choice for prophylaxis against deep venous thrombosis (DVT) in p ost operative patients undergoing both general and orthopaedic surgica l procedures. Despite extensive research, the exact mechanism of the a ntithrombotic activity of LMWHs remains unclear. These agents have bee n shown to activate the fibrinolytic system and to directly inhibit bo th the activity and the generation of factor Xa and thrombin. New evid ence suggests that LMWHs also stimulate the release of endogenous tiss ue factor pathway inhibitor (TFPI) from the vascular endothelium. This study was designed to investigate the role of TFPI in mediating the a ntithrombotic activity of LMWHs. We measured the plasma levels of TFPI in a group of post orthopaedic surgery patients treated with daily su bcutaneous injections of LMWH and a group of patients treated with pla cebo. In the placebo group (n=25), the plasma TFPI levels were slightl y elevated immediately after surgery but returned to their baseline va lue by the fifth post operative day. In contrast, in the group of pati ents treated with LMWH (n=34), the plasma levels of TFPI increased sig nificantly and remained elevated for up to 7 days following surgery. H owever, the TFPI levels in both groups showed wide patient to patient variability. These results indicate that LMWHs stimulate the release o f TFPI into the bloodstream of post surgical patients. This suggests t he importance of TFPI in mediating the antithrombotic activity of LMWH s.