ABNORMAL VITAMIN-K METABOLISM IN THE PRESENCE OF NORMAL CLOTTING FACTOR ACTIVITY IN FACTORY-WORKERS EXPOSED TO 4-HYDROXYCOUMARINS

1 The case histories of two patients exposed to the novel anticoagulants brodifacoum and difenacoum are reported. 2 Abnormal vitamin K1 metabolism, as indicated by elevated vitamin K1 2,3-epoxide plasma concentrations after i.v. administration of vitamin K1, could be detected for more than 18 months after exposure to the anticoagulants. 3 There was a marked prolongation of prothrombin time (> 50 s) in both cases, at the time of exposure. However, subsequent haematological investigations (prothrombin time and vitamin K-dependent clotting factor activity) have been shown to be normal in both cases for at least 18 months. 4 These cases confirm the long-acting nature of brodifacoum and difenacoum and present an apparent dissociation between the effect of coumarin anticoagulants on vitamin K1 metabolism and clotting factor activity.