The role of augmented Hageman factor (factor XII) titers in the cold-promoted activation of factor VII and spontaneous shortening of the prothrombin time in women using oral contraceptives.

Spontaneous shortening of the Thrombotest time and an increase in factor VII activity after cold storage of plasma in plastic vials have been described in the plasma of women using OCAs. The phenomenon if CPA is dependent on the presence of HF (factor XII) and is associated with increased plasma kallikrein activity and the disappearance of C1-INH activity. In the present study, spontaneous CPA and shortening of the prothrombin time were observed in 66% of women using OCAs. The prothrombin time was inversely related to factor VII activity and HF coagulant titer, whereas factor VII activity was strongly associated with the titer of HF. The addition of purified HF to normal plasma to a degree observed in OCA users promoted CPA generation and shortening of the prothrombin time. In contrast, reduction of the HF coagulant titer in the plasma of OCA users to a normal level prevented the rise in factor VII activity and shortening of the prothrombin time after cold storage. These data indicate that a high titer of HF, such as that observed in OCA users, is needed for the spontaneous CPA and add support to evidence linking the extrinsic and intrinsic pathways of clotting. The relationship of this in vitro phenomenon to the pathogenesis of thrombosis in women using OCAs is presently unclear. (J Lab Clin Med 99:363, 1982.)