Characterization of the anticoagulant activities from a Brazilian arrow poison

A recent report indicated that an arrow poison used by the native Indians of Rondonia, Brazil, to kill small animals was associated with profuse bleeding. The arrow poison was prepared from the bark of a tree, known locally as Tike-Uba. We have obtained bark and sap specimens from this tree and have characterized a potent anticoagulant activity in both the crude bark and sap samples as well as in more highly purified preparations. An aqueous extract of the bark significantly prolongs both prothrombin times and activated partial thromboplastin times in plasma based assays. Further fractionation of the bark extract and sap by molecular weight indicated that all of the anticoagulant activity could be isolated in a molecular weight fraction of equal to or greater than 30,000 daltons. The anticoagulant activity was also further purified by C-18 reverse phase chromatography. When highly purified preparations of the anticoagulant activity from the Tike-Uba tree were examined in specific blood coagulation enzyme assays utilizing chromogenic substrates, the highest inhibitory potency was found versus thrombin, followed by factor Xa. These studies establish the presence of a compound(s) in a Brazilian arrow poison, which potently disrupts mammalian blood clotting, and which may account for some of the observed toxicities associated with the arrows.