264 DISTURBANCES OF CIRCULATION 



to the present day as best explaining the facts concerning fibrin forma- 

 tion with which we are familiar. 



It having been shown that calcium facilitates the formation of fibrin, 

 Pekelharing advanced the idea that the prothrombin does not exist in the 

 plasma, but is liberated from the leucocytes, and, combining with the 

 calcium of the plasma, forms the thrombin. Morawitz considers three 

 substances necessary for the formation of thrombin : (1) the prothrombin 

 or thrombogen, which he believes originates in the blood-plates ; (2) the 

 zymoplastic substance or thrombokinase, which is liberated from the leuco- 

 cytes into the plasma ; (3) calcium salts. The chief differences, there- 

 fore, are not concerning the nature of the thrombin, but the manner of 

 its origin, and whether the prothrombin arises from the leucocytes, the 

 plasma, or the platelets. It seems quite probable, however, that pro- 

 thrombin may occur in all these constituents of the blood ; since 

 coagulation occurs in the lymph, which contains no platelets, the pro- 

 thrombin evidently is not derived solely from these elements. It will 

 not serve our purpose, however, to go further into the hypotheses and 

 disputes over these questions, which are detailed more fully in the 

 literature previously cited. 



The question has been raised as to whether the leucocytes secrete 

 their fibrin-forming constituent (be it thrombokinase or prothrombin is 

 a matter of minor importance to the pathologist) or liberate it only after 

 their disintegration. So far as pathological processes go, the latter seems 

 to be the case, the disintegration apparently occurring whenever the 

 leucocytes come in contact with a foreign body or with dead and injured 

 tissues. J 



Tissue Coagulins, Among the other points that are of importance 

 in pathological conditions is the fact that not only leucocytes, but also 

 tissue-cells, can liberate fibrin-forming substances (coagulins is the non- 

 committal term applied by Loeb). These tissue-coagulins are present in 

 tissue extracts and are liberated whenever the tissues are injured ; muscle 

 is rich in coagulin, as are also the liver and kidney, and, which is partic- 

 ularly important, the blood-vessel wall (L. Loeb). Pieces of these 

 tissues placed in contact with fibrinogen solution will bring about prompt 

 clotting. Another important fact is that the coagulins, whether derived 

 from leucocytes or from the tissues, have a certain degree of specificity 

 that is, they act solely or most rapidly with fibrinogen of blood of the 

 species from which they are obtained. 2 In some instances this specific- 

 ity is absolute, but more generally (particularly in the mammalia) it is 

 only relative. Loeb also found that the amount of tissue coagulin was 

 not decreased in organs altered by phosphorus-poisoning, although during 

 experimental autolysis the coagulins disappear. When tissue coagulins 

 and blood coagulins act together, the effect is greater than the sum of 

 their independent actions, indicating the probability that they combine 

 in some way to produce a particularly active coagulin. The blood 

 coagulins are quite different from the tissue coagulins in many important 

 respects, and the coagulins cannot be looked upon as a single substance 

 of different origins. 



Blood-platelets. 3 It is still undetermined just what part the platelets 



1 See L. Loeb, loc. cit. 



2 Leo Loeb, Univ. of Penn. Med. Bull., 1904 (16), 382; Muraschew, Deut. 

 Arch. klin. Med., 1904 (80), 187. 



3 Earlier literature, see Schwalbe, Ergebnisse der Pathol., 1902 (8), 150 : 

 and Lowit, ibid., 1895 (2), 642. 



