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.
Department of Haematology, Haematological Research Laboratory, Ullevaal University Hospital, Oslo, Norway. p.m.sandset@ioks.uio.no
P M
PM
Sandset
B
B
Bendz
J B
JB
Hansen
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