γ‐Carboxyglutamate excretion and warfarin therapy

The urinary excretion of gamma-carboxyglutamic acid (Gla), the amino acid involved in the vitamin K-dependent calcium binding of prothrombin and clotting factors VII, IX, and X, was studied in warfarin-anticoagulated patients. An isotope dilution procedure was developed for the measurement of free urinary Gla with the use of prior anion-exchange chromatography to separate and concentrate the free Gla from whole urine and subsequent automated amino acid analysis. Eight subjects on stable warfarin anticoagulant therapy and 11 comparable control subjects with normal coagulation were examined. Urinary Gla excretion was reduced in patients on warfarin anticoagulant therapy (p = 0.001) and the urinary Gla level correlated (r = -0.73, p = 0.001) with plasma prothrombin time. It is concluded that decreased urinary Gla in warfarin-treated patients is related to coagulation status and may be a clinically useful parameter.