The procoagulant effect of zinc on fibrin clot formation

The influence of Zn+2 on fibrin clot formation was investigated by measuring its effect on the clotting times of fibrinogen exposed to thrombin. It was observed with either human or bovine thrombin that 0.01-0.1 mM Zn+2 induced significant reductions of clotting times in a concentration-dependent manner. The procoagulant effect of Zn+2 occurred in the presence of Ca+2 but was inhibited by metal chelating agents. Higher levels of Zn+2 (greater than 0.2 mM final concentration) were required to accelerate thrombin-induced clot formation in the presence of citrate or oxalate. Similarly with oxalated human plasma, greater than 0.2 mM Zn+2 decreased the clotting time. Cations such as Mg+2 and Mn+2 caused little change in clotting times. As an extension of these findings, we examined the effect of Zn+2 on the inhibition of thrombin by antithrombin-III (AT-III). The presence of as little as 0.006 mM Zn+2 in an incubating mixture of thrombin and AT-III severely reduced the inhibitory activity of AT-III towards thrombin. It was observed that the relative intrinsic fluorescence emission of human thrombin decreased upon exposure to Zn+2 but was unaffected by Mg+2 or Mn+2. It is suggested that Zn+2 can form a complex with thrombin, which results in altered reactivity towards fibrinogen and decreased inhibition by AT-III.