RETARDATION OF COAGULATION. 325 



lation, obtained by CONRADI 1 in autolysis, which are probably antithrom- 

 bins, seem to act in a different way from the proteoses, and cannot for 

 the present be made use of in explaining this question. 



There are a large number of researches on the action of proteoses 

 and of other similar retarding substances by a great number of different 

 investigators, especially by GLEY AND PACHON, SPIRO, MORAWITZ, NOLF, 

 DELEZENNE, DOYON and collaborators. 2 We can say with certainty 

 that the action is indirect, and that the liver is important for the process. 

 The non-coagulability of " peptone-blood " seems to be due to several 

 reasons, but it has not been thoroughly explained. On the one hand 

 such blood contains an antithrombin, and on the other it seems as if the 

 formation of thrombin is not sufficient, although the plasma contains 

 the necessary conditions for the thrombin formation, as it coagulates as 

 a rule on dilution with water or the addition of a little acid. This last 

 behavior speaks, according to MELLANBY, S for the assumption that the 

 liver, because of the proteose injection, gives up an excess of alkali to the 

 blood thus preventing the coagulation of the peptone-blood. Opinions 

 in regard to the occurrence of an antithrombin in the peptone- 

 plasma seem to be unanimous, and we have gained considerable 

 experience in regard to the formation of this antithrombin. According 

 to NOLF, the peptones (more correctly the proteoses) cause an altera- 

 tion in the leucocytes and the walls of the vessels, and a substance is 

 secreted which brings about, in the liver, the formation of antithrombin. 

 According to DELEZENNE the proteoses bring about a destruction of 

 leucocytes, and thereby a substance accelerating coagulation and another 

 having a retarding action is set free. The first is destroyed by the liver, 

 and hence the action of the retarding substance (the antithrombin) is 

 obtained. DOYON and co-workers have also shown that the isolated 

 washed liver on transfusing normal arterial blood, gives off a thermo- 

 stable antithrombin, which behaves like a nucleoprotein. That the liver 

 takes part in the retardation of coagulation is positively known. 



x Pick and Spiro, Zeitschr. f. physiol. Chem., 31; Underbill, Amer. Journ. of 

 Physiol., 9; Popielski, Arch. f. expt. Path. u. Pharm., Suppl. 1908, Schmiedeberg's 

 Festschrift; Conradi, Hofmeister's Beitrage, 1. 



2 Grosjean, Travaux du laboratoire de L. Fredericq, 4, Liege, 1892; Ledoux, ibid., 

 5, 1896; Nolf, Bull. 1'Acad. roy. de Belgique, 1902 and 1905, and Biochem. Centralbl., 

 3; and footnote 1, p. 318; Spiro and Ellinger, Zeitschr. f. physiol. Chem., 23; Fuld 

 and Spiro, 1. c.; Morawitz, 1. c. The works of the above-mentioned French investi- 

 gators can be found in Compt. rend. soc. biol., 46, 47, 48, 50, and 51, and Arch. d. 

 Physiol. (5), 7, 8, 9, and 10; see also especially Delezenne, Arch. d. Physiol. (5), 10; 

 Compt. rend. soc. biol., 51, and Compt. Rend., 130; Doyon, Compt. rend. soc. biol., 

 68, with Morel and Policard, ibid, 70. 



3 Journ. of Physiol., 38. 



