The action of p-aminosalicylic acid on prothrombin time in man.

A lengthening in prothrombin time by giving salicylates was first observed in the animal experiments of Link, Overman, Sullivan, Huebner, and Scheel (1943). This result, and a comparison of the structures of coumarin-like anticoagulants (Overman, Stahmann, Huebner, Sullivan, Spero, Doherty, Ikawa, Graf, Roseman, and Link, 1944), led Link to conclude that dicoumarol (3,3'-methylenebis [4hydroxycoumarin]) acts on breaking down in vivo to the chemically related salicylic acid. The experimental findings of Link and his colleagues have been amply confirmed and extended to man (Meyer and Howard, 1943; Shapiro, Redish, and Campbell, 1943 ; Clausen and Jager, 1946; Dibenedetto Dell' Aquila and Lojacono, 1946; Owen and Bradford, 1946; Zimmerman and Shapiro, 1946; Nitshe, Gerarde, and Deutsch, 1947). Their hypothesis, however, has not found complete acceptance, although the only direct evidence against it is the absence of salicylates in the urine after treatment with dicoumarol (Lester, 1944). Jaques and Lepp (1947) found that rabbits given salicylate by mouth, or dicoumarol either by mouth or intravenously, showed a lengthening of prothrombin time. Intravenous salicylate had no effect, neither did salicylate given orally together with succinylsulphathiazole. They advanced the view that salicylate may be converted to a dicoumarol-like substance by bacterial synthesis in the intestine. It was hoped that a comparison of blood salicylate levels and prothrombin times in patients receiving salicylate and in those receiving dicoumarol would yield further information on their mode of action. During this investigation, which was making slow progress owing to the lack of suitable patients, the analogous case of p-aminosalicylic acid (P.A.S.), used in the treatment of tuberculosis, was given consideration.