IN 1909 Biedl & Kraus, and Arthus independently, reported a marked increase in the clotting time of the blood of dogs in anaphylactic shock. Earlier, in 1880, Schmidt-Miilheim had noted the increase in the clotting time of the blood which followed, an intravenous injection of Witte peptone into dogs. This observation was quickly confirmed, and already by the time of Morawitz's review on the subject of blood clotting in 1905, a considerable literature had accumulated on the nature of the blood changes induced by peptone. It is not surprising therefore that the prolonged coagulation time noted in anaphylaxis in the dog should be compared with, and considered to be fundamentally the same as, that accompanying peptone shock. This comparison appears to have been first made by de Waeles, but he was severely criticized and his views did not meet with general acceptance. Fano had suggested that peptone caused the production within the organism of a substance which was responsible for this prolongation of the clotting time, and that this substance was active both in vivo and in vitro. The work of a number of investigators, including Delezenne, Contijean, Doyon, Popielski and Nolf, pointed to the liver as a source of this substance (the above mentioned references will be found in the reviews of Morawitz [1905] and W6hlisch [1929]). While some investigators considered the anticoagulant to arise from a number of different tissues, Nolf, in particular, stressed the view that it was solely of hepatic origin. Certain of these earlier workers had attempted to identify this anticoagulant, but it remained for Howell [1925] to suggest that it might be heparin, the anticoagulant he had obtained from dog liver. Recent investigations have further supported Howell's contention that heparin is responsible for the incoagulability of the blood in peptone shock [Quick, 1936; Wilander, 1939] and also in anaphylactic shock [Eagle, Johnston & Ravdin, 1937].
