Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A.

Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa complexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate haemostasis initiated by FVIIa/TF thereby compensating for impaired FIX/FVIII-dependent coagulation.

The effect of recombinant aprotinin on t-PA-induced bleeding in rats.

High dose aprotinin administered during cardiopulmonary bypass (CPB) has been shown to reduce post-operative bleeding substantially. The exact mechanism of action is still debated. A reduction in fibrinolytic activity by inhibition of plasmin generated during CPB may be the primary mode of action.

The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits.

Disseminated intravascular coagulation (DIC) is a common complication in sepsis, and may result from endotoxin-induced exposure of tissue factor on the surface of monocytes and endothelial cells. Tissue factor pathway inhibitor (TFPI) is a factor Xa-dependent feedback inhibitor of the tissue factor-factor VIIa complex. In the present study the effect on DIC of a two-domain TFPI analogue (2D-TFPI), consisting of the first two Kunitz domains of TFPI but lacking the third domain, was tested.

Pharmacokinetics of recombinant factor VIIa in the rat--a comparison of bio-, immuno- and isotope assays.

Recombinant human factor VIIa (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 micrograms/kg 125I-rFVIIa i.

Pharmacokinetics of full length and two-domain tissue factor pathway inhibitor in combination with heparin in rabbits.

Tissue factor pathway inhibitor (TFPI) is a feed back inhibitor of the initial activation of the extrinsic pathway of coagulation. In humans, injection of heparin results in a 2-6 fold increase in plasma TFPI and recent studies suggest that TFPI may be important for the anticoagulant activity of heparin. Full length (FL) TFPI, but not recombinant two-domain (2D) TFPI, has a poly cationic C-terminus showing very strong heparin binding.