THE ANTICOAGULANTS EFFECTIVE IN VIVO WITH SPECIAL REFERENCE TO HEPARIN AND DICUMAROL

Abstract

The normal blood antithrombin of the blood, closely associated with the albumin fraction, does not inhibit or retard coagulation, but merely inactivates thrombin. Quantitative methods have been developed for its detn., but the significance of its variation in the blood remains obscure. Heparin, the natural physiological anticoagulant, is a compound closely related to mucoitin poly-sulfuric acid. Due to its strongly acidic character, it forms complexes with various proteins and other biological compounds. Heparin per se is not an antithrombin, but with a co-factor present in serum albumin forms a strong thrombin-inactivating complex. Heparin in inhibiting the conversion of prothrombin to thrombin likewise requires a cofactor which is present in the plasma. Heparin prevents the agglutination of platelets, probably by virtue of its anticoagulant action. The function of heparin in the body has not been determined. It is liberated during anaphylactic and peptone shock, but the mechanism whereby this is brought about is still obscure and the purpose of this physiological response has not been ascertained. Anti-thromboplastin present in the blood is abnormally increased in hemophilic blood. Dicumarol is the toxic principle isolated from spoiled sweet clover hay. It is a coumarin derivative which had not hitherto been known to occur in plants. When dicumarol is administered orally or intraven. to man or animals, it causes a gradual but severe decrease of the prothrombin of the blood (or more accurately of component B of prothrombin). Several days are required for the production of its full effect, and recovery is equally slow. Evidence suggests that vit. K has some antagonistic action against dicumarol. The hypopro-thrombinemia produced by the drug can be temporarily alleviated by transfusion. Dicumarol has no toxic action other than depressing the prothrombin except in excessive dosage. It is probable that some of the pathological findings in fatal cases of dicumarol poisoning can be attributed to tissue anoxia due to the severe anemia after excessive hemorrhage. Salicylates especially when given to animals on a low vit. K diet depress the prothrombin of the blood but to a much smaller degree than dicumarol. Sulfaguani-dine and succinylsulfathiazol also cause a hypoprothrom-binemia, but the action is due to a depression of the synthesis of vit. K by the bacteria of the intestines and not to a direct action on the synthesis of prothrombin.