The effects of salicylate on enzymes of vitamin K metabolism

Abstract

The mechanism of salicylate-induced hypoprothrombinaemia has been investigated in the rat. Salicylate administration produced an increase in the percentage of the total liver vitamin that was present as vitamin K 2,3-epoxide, but the addition of salicylate did not influence vitamin K epoxide reductase activity in-vitro. Neither did it influence vitamin K-dependent carboxylase or vitamin K epoxidase activity. Both cytosolic and microsomal DT-diaphorase activities were, however, inhibited about 50% by 75 microM sodium salicylate. Salicylate inhibition was also observed when vitamin K quinone and NADH or dithiothreitol were used to support carboxylation. To achieve 50% inhibition required 0.5 mM salicylate with NADH as a reductant and 4 mM salicylate when dithiothreitol was the reductant. These results suggest that the main effect of salicylate on vitamin K metabolism is to inhibit quinone reductases and may be useful in explaining the inhibition of the biosynthesis of vitamin K-dependent clotting factors that occurs in salicylate-induced hypothrombinaemia. These data also demonstrate that the percentage of total liver vitamin present as vitamin K epoxide can be increased by agents that do not have a direct effect on the vitamin K epoxide reductase in-vitro.

Inadvertent Exaggerated Anticoagulation Following Use of Bismuth Subsalicylate in an Enterally Fed Patient Receiving Warfarin Therapy

“…However, this unique polymorphism is only prevalent in about 8% of Caucasians 17 . Older literature suggested that salicylates may have a direct hypoprothrombinemic effect 18 via their ability to inhibit quinone reductases thus inhibiting the biosynthesis of vitamin K‐dependent clotting factors 19 . Further study is required regarding this relatively unknown pharmacodynamic effect.…”

Bismuth Subsalicylate Coagulopathy in a Patient with Chronic Liver Disease

“…A study investigating the mechanism of salicylate-induced coagulopathy in rats suggests that salicylates do so by inhibiting vitamin K quinone reductase, an enzyme necessary in the biosynthesis of vitamin K-dependent coagulation factors, particularly prothrombin [22]. Patients with underlying liver disease and impaired metabolism of vitamin K, such as the present case, may be predisposed to coagulopathy from salicylates.…”