A spectrum of partially carboxylated prothrombins in the plasmas of coumarin-treated patients.

Prothrombin has been purified from the plasmas of normal human donors and from patients ingesting coumarins. Equimolar amounts of normal prothrombin or coumadin-induced prothrombin were incubated with phospholipid micelles in the presence of Ca2+. Subsequent gel filtration of the incubation mixtures demonstrated that all of the normal prothrombin was bound to the phospholipid; only half of the coumadin-induced prothrombin was bound. Normal prothrombin contains approximately 10 mol of gamma-carboxyglutamic acid per mol of prothrombin. The coumadin-induced prothrombin which was bound to phospholipid contains approximately 6.5 mol of gamma-carboxyglutamic acid per mol of prothrombin while that which failed to bind to phospholipid has only 2.8 mol of gamma-carboxyglutamic acid per mol of zymogen. Thus, partially carboxylated prothrombins exist in the plasmas of coumarin-treated patients. Furthermore, there is a striking electrophoretic heterogeneity in the prothrombin preparations from the plasmas of the coumadin-treated patients. This most likely results from a wide spectrum of abnormal prothrombins with varying quantities of gamma-carboxyglutamic acid per mol of zymogen.