A Hemorrhagic Syndrome Induced by Derivatives of 3-Hydroxy-1,4-Naphthoquinone. ∗

Summary

1. A fatal hemorrhagic syndrome accompanied by marked hypoprothrombinemia was produced in rats by the administration of 3 2-substituted-3-hydroxy-1,4-naphthoquinones.

2. These compounds produced only minimal pathologic changes in the liver, caused no measurable destruction of prothrombin in vitro, and possessed only slight bacteriostatic activity against Escherichia coli, the principal source of vitamin K in the gut.

3. The hemorrhagic and toxic properties of at least one of the compounds studied, SN 5090, were antagonized partially by 2 -methyl-1,4-naphthoquinone and completely by vitamin K₁. On the basis of this finding it was postulated that these 2-substituted-3-hydroxy-1,4-naphthoquinones, such as SN 5090, compete with the K vitamins in processes essential to prothrombin formation and by displacing these vitamins produce the hemorrhagic syndrome described here.