The Interaction of Factors VIII and IX

Abstract
Using purified preparations of Factors VIII, IX and contact product, the coagulant activity with ability to activate Factor X is studied. Definite activity develops in these mixtures and no activity is detected if either Factor VIII or IX is omitted. Attempts to relate the amounts of Factor-X activator to the initial concentrations of Factors VIII or DC have been confused by the obviously complex nature of the overall reaction. The production of activator in the mixtures involved a variable initial lag phase and the activator once formed was unstable. The addition of trace amounts of thrombin to the initial mixtures abolished the lag phase (Fig. 3) without apparently providing activity capable of replacing either of the main constituents (Factors VIII and DC). It seems possible that trace amounts of thrombin may be essential for the reaction between Factors VIII and DC and that in mixtures to which no thrombin has been added such trace amounts develop from pro-thrombin contaminating the reagents. The lag phase may be controlled by the extent of this contamination. Despite these complications there seems little doubt that an activator of Factor X develops in a mixture of purified Factors VIII and IX and that this activator is derived from Factor VIII.