COAGULATION. 429 



sion, therefore, is justified that the active ferment is formed after 

 the blood is shed. Schmidt subsequently designated this ferment 

 as thrombin. A third fact of essential importance in theories of coag- 

 ulation is that soluble calcium salts are necessary to the process. 

 This discovery was made definitively by Arthus and Pages,* who 

 showed that blood received into an oxalate solution, so as to 

 precipitate the calcium, does not clot. Subsequent addition of a 

 solution of a calcium salt induces clotting promptly. 



We may say, therefore, that there are three fibrin factors which 

 are undoubtedly concerned in the production of fibrin, namely, 

 fibrinogen, calcium salts, and thrombin. Two of these exist in the 

 circulating blood, one of them, the ferment, is formed after the blood 

 is shed. Obviously, therefore, we may conclude that the main 

 reason for the clotting of the blood when shed is the formation of 

 thrombin. The difficulties in the way of an adequate explanation 

 of the formation of the thrombin and its mode of action are very 

 great. 



The theories that have been proposed in recent years are numer- 

 ous and conflicting.* It has long been believed that the for- 

 mation of the thrombin is initiated by the breaking down of the 

 formed elements in the blood, the leucocytes and the blood plates. 

 Concerning the amount of destruction of leucocytes in shed blood 

 opinions still differ. While some observers report that they dis- 

 integrate in large numbers when the blood escapes from the ves- 

 sels, others deny that they show any marked immediate effect of 

 such a change in environment. Concerning the blood plates there 

 can be no doubt. Immediately after the shedding of blood and 

 within the time that precedes normal coagulation these structures 

 agglutinate and then dissolve or disintegrate. There is much 

 evidence to show that the fibrin is deposited first in the neighbor- 

 hood of these agglutinated masses of blood plates, and moreover 

 that any reagent or condition that prevents or retards the breaking 

 down of the plates prevents or delays the clotting of the blood. 

 We may believe, therefore, that the blood plates (and leucocytes) 

 give rise to some substance or substances necessary in the forma- 

 tion of the thrombin. 



According to a theory proposed by Pekelharing and formerly 

 much quoted, it was suggested that the dissolution of the formed 

 elements liberates a nucleoprotein which then combines with the 

 calcium present to form a calcium nucleoprotein compound which 



* "Archives de physiologic normale et pathologique," fifth series, 2, 739, 

 1890. 



f For recent theories and literature see Morawitz, 'Beitriige zur chem. 

 Physiol. u. Pathol.," 4, 381, 1904, and "Deutsches Archiv f. klin. Med.," 

 1904, Ixxix., 1 and 215; Fuld, ' Zentralblatt f. Physiol.," 17, 529, 1903; Nolf, 

 "Arch, internat. de Physiol.," 1906, iv., 165; Loeb, ''The Medical News," 

 April 1, 1905. 



