Abstract
A new inhibitor of blood coagulation, calphobindin (CPB; MW 34000) isolated from human placental tissue by EDTA extraotion was pharmacologically studied as an anticoagulant. CPB in concentrations ranging 3 to 30μg/ml gave only a slight inhibitory effect on human intact whole blood clotting time (WBCT; r+k=28min) estimated with thromboelastograph. A significant prolonging effect of CPB, however, was observed against tissue factor (TF)-added WBCT in a concentration of 1μg/ml, resulting in a complete neutralization of added TF (2μg/ml) by 3 to 10μg/ml of CPB. Heparin gave a significant prolonging effect not only on intact WBCT but on TF-added WBCT in a concentration of 0.03U/ml and a severe blood coagulation defect in a concentration of 0.3U/ml.In a rat DIC model induced by TF iv infusion (20mg/kg) for 60min, reduction of plasma fibrinogen level (50 to 60%) was protected by simultaneous administration of 20mg/kg of CPB. Heparin also gave a prophylactic effect on fibrinogen reduction in a dose of 200U/kg.These results suggest that CPB seems to be able to medicate the tissue factor poison caused by inflow of TF into blood stream.
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