Metabolism of the coagulation factors of the prothrombin complex in hypothyroidism in man

The metabolic rate of prothrombin, factors VII, IX and X, was studied in nine hypothyroid patients. Disappearance rates of the four vitamin-K-dependent factors, called the prothrombin complex, were measured after assumedly complete blocking of their synthesis with adequate doses of a coumarin congener (acenocoumarol). Reappearance rates were assessed by induction of synthesis with high doses of vitamin K1 (phytomenadion) when stable hypocoagulability had been achieved. Normal values for these rates were derived from earlier studies in our laboratory. In hypothyroid patients the rates of both disappearance and reappearance were significantly slower for all factors tested. Practical consequences of these observations are discussed. The initial level of factor-IX activity in all nine patients was substantially lower than in normal individuals. Therapy by thyroxine-substitution led to normal levels of factor-IX. This implies a divergency in the retardation of the breakdown and production rates in hypothyroidism. The reappearance rate was indeed found to be more retarded than the disappearance rate.