Experimental haemorrhagic effect of two-domain non-glycosylated tissue factor pathway inhibitor compared to low molecular weight heparin.

The glycosylated multivalent three-domain Kunitz inhibitor TFPI is a natural inhibitor of tissue factor-FVIIa complex in the presence of FXa. TFPI has an experimental antithrombotic capacity indistinguishable from LMWH in a prophylactic dose, regardless of glycosylation and of the third domain. An inherited equilibrium between antithrombosis and haemorrhage exists.

The appearance of endothelium in small arteries after treatment with 5-fluorouracil. An electron microscopic study of late effects in rabbits.

Cardiotoxicity is an unexplained toxic manifestation of 5-fluorouracil (5-FU). Its possible mechanism could be a direct cytotoxic effect on the vascular endothelium. We have tested this hypothesis in an experimental study in rabbits, using scanning and transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear).

The haemorrhagic effect of low molecular weight heparins, dermatan sulphate and hirudin.

In a randomized, blind study the primary effect on haemostasis after intravenous administration of dermatan sulphate (DS), recombinant hirudin (r-hirudin) and four commercial low molecular weight heparins (LMWHs) (nadroparine, enoxaparin, dalteparin and tinzaparin) was investigated in rats and compared with saline (control). The tail bleeding time, the bleeding from the gastric mucosa [the mucosal bleeding time (min) and the mucosal bleeding (microliter)] as well as changes in activated partial thromboplastin time, antifactor IIa and Xa activities were investigated. DS and r-hirudin were investigated in a dose potentially suitable in thomboprophylaxis and the LMWHs in doses recommended by the manufacturers for thromboprophylaxis, adjusted to body weight.

Dextran and release of prostacyclin from ex vivo perfused rabbit arteries and veins.

The effects of dextran on the haemostatic system lead to prolongation of the bleeding time. To observe if the coating of endothelial cells by dextran influences the release of prostacyclin from the vessel walls in response to ex vivo perfusion, dextran 70 (1 g/kg b.w.

Prostacyclin and thromboxane release from the vessel wall--comparison between an incubation and a perfusion model.

Prostacyclin (measured as its stable degradation product 6-keto-PGF1 alpha) and thromboxane (measured as its stable degradation product TxB2) produced by the vascular wall were measured by radioimmunoassay (RIA). Four pieces from the rabbit aorta and four from the caval vein were used. One piece was incubated in Hank's balanced salt solution (HBSS), one piece with additional indomethacin, and the other pieces were mounted in a perfusion system so that only the endothelium was exposed to the buffer solution with or without indomethacin.