Physiological function of tissue factor pathway inhibitor and interaction with heparins.
Tissue factor pathway inhibitor (TFPI) is now recognized as a major physiological anticoagulant. Its main role is to modulate factor VIIa/tissue factor catalytic activity. Another important role is to potentiate the effect of heparins. TFPI is released from the vascular endothelium after injection of either unfractionated heparin (UFH) or low-molecular-weight heparins (LMWHs), which may then provide high concentrations of TFPI at sites of tissue damage and ongoing thrombosis. In dilute prothrombin-time-based assays, released TFPI contributes approximately one-third to the anticoagulant effect of heparin, the remaining being accounted for by antithrombin. Released TFPI, but not plasma TFPI, contains the basic carboxy-terminal tail which is important for the anticoagulant effect. UFH and LMWH exert differential effects on intravascular TFPI. UFH, but not LMWH, given in therapeutic doses, is associated with a progressive depletion of TFPI, which is associated with a strong rebound activation of coagulation after cessation of treatment. Such depletion may explain the apparent superior efficacy of LMWH observed in clinical trials.
Sandset
P M
PM
Department of Haematology, Haematological Research Laboratory, Ullevaal University Hospital, Oslo, Norway. p.m.sandset@ioks.uio.no
Bendz
B
B
Hansen
J B
JB
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism*; D000991:Antithrombins / Q000502:physiology; D005591:Chemical Fractionation; D004730:Endothelium, Vascular / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000378:metabolism; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D011517:Prothrombin Time; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D006583:Hexadimethrine Bromide; D006493:Heparin