Anticoagulant and antiprotease activities of aprosulate sodium, a new synthetic polyanion, in human plasma and purified systems.

Aprosulate sodium, a new synthetic polyanion, was evaluated for anticoagulant/antiprotease activities in vitro. Aprosulate prolonged activated partial thromboplastin time (aPTT), Heptest and thrombin time (TT) with the sensitivity order of aPTT > Heptest > TT. Prothrombin time (PT) was hardly affected by the agent. Since these results indicated that inhibition of the intrinsic coagulation cascade was important for the anticoagulant activity of aprosulate, amidolytic assays were subsequently performed to characterize antiprotease activities of the agent in the common and intrinsic pathways. Aprosulate inhibited amidolytic activity of thrombin in the presence of heparin cofactor II, but was devoid of direct and antithrombin-mediated anti-factor Xa, and direct anti-factor XIIa activities. However, aprosulate was found to be a potent inhibitor of amidolytic activity of factor Xase (IXa/VIIIa). These data suggest that the direct anti-factor Xase activity of aprosulate primarily contributes to its anticoagulant activity in the intrinsic coagulation cascade.