Is tissue factor pathway inhibitor involved in the antithrombotic effect of heparins? Biochemical considerations.
Tissue factor pathway inhibitor (TFPI) is released into the circulation after intravenous or subcutaneous injection of heparin or low-molecular-weight heparin (Logiparin) in humans. The plasma concentration of TFPI is increased 2- to 4-fold by a prophylactic dose of Logiparin, and this excess TFPI remains in the circulation only in the presence of the heparin. TFPI and heparin show strong synergism in clotting assays at concentrations obtained after heparin injection in humans. Animal studies have demonstrated that TFPI by itself has antithrombotic properties. It is concluded that the release of TFPI may contribute significantly to the antithrombotic effect of heparin.
Ostergaard
P
P
Heparin Research Laboratory, Biopharmaceuticals Research, Novo Nordisk A/S, Gentofte, Denmark.
Nordfang
O
O
Petersen
L C
LC
Valentin
S
S
Kristensen
H
H
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000097:blood*
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin