The one-stage prothrombin time of oxalated plasma was prolonged on incubation with disodium EDTA. This was due to the destruction of Ac-Globulin or the inhibition of its production from a precursor stage. There was a similar change with disodium calcium EDTA, indicating some metal other than calcium was probably being chelated.
A marked prolongation of the prothrombin time of oxalated plasma occurred on incubation with cupric, ferrous, stannous, cobaltous, and magnesium EDTA, but manganous, zinc and nickel EDTA produced no prolongation of the prothrombin time. This would support the concept that a metal ion may be concerned with the maintenance of Ac-Globulin or its conversion into an active form.
The cobaltous, cupric, ferrous and ferric ions produced a prolongation of the prothrombin time. This effect was corrected by the use of prothrombin free plasma except in the case of cobalt. The manganous, barium and nickel ions did not prolong the prothrombin time and nickel was effective in maintaining the prothrombin time at its original level. Its most effective concentration was .001 M. At higher concentrations it produced a prolongation which was not corrected by the addition of prothrombin-free plasma.