Phenformin and ethyloestrenol in recurrent venous thrombosis

Altogether 75 patients, 60 of whom had recurrent idiopathic deep venous thrombosis, 10 recurrent superficial thrombophlebitis and 5 retinal venous thrombosis, were given a combination of 100 mg phenformin and 8 mg ethyloestrenol a day for periods varying between 3 and 48 months (mean 16.2). Initially, all the patients had an abnormally low plasminogen activator content in the walls of superficial veins and/or a decreased capacity to release plasminogen activator from the vein walls on venous occlusion of the arms. The combination elicited a significant increase in the spontaneous fibrinolytic activity and in the local fibrinolytic activity during standardized venous occlusion of the arms (assayed on fibrin plates) after treatment for 3 months (p less than 0.001). These activities then remained normal throughout the observation period. In 65 of the 75 patients studied, the plasminogen activator level in the vein wall (histochemically assayed by the method of Pandolfi) was abnormally low intitially. The level had increased significantly after treatment for 3 months (p less than 0.001). After treatment for 12 months all the patients except 2 were normal. The patients in this material had had 2-20 episodes of venous thrombosis, the most recent 5 years before the institution of treatment, in spite of dicoumarol treatment. During treatment 9 thrombotic episodes occurred; in 5 of these patients the fibrinolytic activity of the vessel wall was not normal at the time of the recurrence. Except in 1 patient, who developed lactic acidosis, the side-effects were not severe.