Abstract
The anticoagulant and antithrombotic effects of a glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM) expressed in C-127 cells were investigated.
Among several species of blood tested, GAG-UTM induced a 2-fold prolongation at 0.24μg/ml in human whole blood clotting time.
Following the injection of 125I-fibrinogen, the rat was infused with Tissue factor (TF) 30mg/kg/hr intravenously (i.v.), and the macro-autoradiogram was conducted. Marked accumulations of 125I-fibrin comprising microthrombi were observed in major organs such as kidney, spleen, liver and lung. The tissue/blood (T/B) ratio of the radioactivity was used to indicate the distribution of thrombi. TF infusion gave rise to 1.1 through 4.7 in the T/B values.
In the above treatment, i.v. infusion of GAG-UTM (10 to 300μg/kg/hr) dose-dependently decreased the T/B values. Moreover, significant improvement of the platelet counts and plasma fibrinogen levels were induced by GAG-UTM administration (more than 30μg/kg/hr).
Those results indicate that GAG-UTM shows an excellent inhibitory effect on TF-induced thrombus formation, and it markedly normalizes the bleeding tendency caused by TF-infusion.
It seems that GAG-UTM may be a potent antithrombotic agent without affecting bleeding tendency in clinical use.
