CORRECTION OF DEFECTS IN CLOTTING ACCELERATOR ACTIVITY BY ADMINISTRATION OF METHIONINE AND VITAMIN K AND OF A NEW SULFHYDRYL-SUBSTITUTED METHYLNAPHTHOQUINONE, VITAMIN K-S(II)12

Abstract

Experimental and clinical studies in normal and cholecystnephrostomized dogs on normal, protein and methionine-free diets, in partially hepatectomized rats and in human patients, indicate that accelerator activity in blood coagulation is influenced strikingly by the concomitant administration of DL-methionine and vitamin K. Because of this synergistic effect, S-(2-methyl-l, 4-naphthoquinonyl-3)-[beta]-mercaptopropionic acid, designated vitamin K-S (n), was designed to incorporate both sulfur and propionic acid into the vitamin K molecule in the 3-position. The accelerator response to this compound, orally or intravenously, is similar to that of methionine plus vitamin K. Two patients with severe hemorrhagic diatheses associated with deficiencies of accelerator factors were treated with vitamin K-S(II). Accelerator levels returned to normal and hemorrhagic manifestations disappeared completely. In one of the patients, studied over a 6-year period, DL-methionine (oral) and vitamin K (intravenous), administered concomitantly, repeatedly exerted a corrective effect on accelerator levels, whereas fresh and banked blood and massive doses of vitamins K and K1 had no effect. The effect of vitamin K-S(II) on prothrombin is negligible except in vitamin K deficiency states.