224 THE BLOOD 



a firm coagulum, from which a perfectly clear serum is eventually 

 separated. 



It must be concluded, therefore, that calcium plays an important 

 part in clotting. The controversy regarding the precise action of this 

 salt initiated by Pekelharing, 1 has finally been settled by Hammarsten, 2 

 who has proved that it plays an important part during the first stage 

 of this process. This deduction is based upon the observation that 

 a calcium-free solution of fibrinogen may be made to coagulate by 

 means of calcium-free thrombin, while the latter cannot be formed in 

 the absence of soluble calcium salts. Again, oxalate plasma contains 

 no fibrin ferment, but gives rise on cooling to an inactive precipitate 

 in which active thrombin may be generated at any time by the addi- 

 tion of a soluble calcium salt. Obviously, therefore, the calcium serves 

 the purpose of activating the pro thrombin of the plasma, but when 

 fully formed, the action of the thrombin cannot be hindered in any 

 way by the precipitation of this salt. 



Solutions of strontium citrate, sodium citrate or sodium metaphos- 

 phate also exert a retarding influence upon coagulation. Thus, if 

 sodium citrate is added to blood in the presence of a calcium salt, a 

 double salt of sodium-calcium-citrate is formed, and, as the calcium 

 is retained in this union as a part of the acid radical, it cannot partici- 

 pate in the process of clotting. A similar result may be obtained with 

 sodium fluorid in solutions of 3 parts of this salt to 1000 parts of blood. 

 If thrombin is added to this mixture, coagulation sets in immediately. 

 The calcium precipitates a portion of the protein, but invariably 

 incites clotting if added in excess. To begin with, therefore, the cal- 

 cium seems to be held as a fluorid in combination with a part of the 

 protein, until its uncombined portion is enabled to manifest its char- 

 acteristic action. Thus, the fluorid binds the calcium in the same 

 manner as the oxalates. 



Substances of Animal Origin. The circulating blood of the 

 mammals, and especially that of the dog, may be rendered non-coagu- 

 lable by the procedure of peptonization which consists in injecting a 

 solution of commercial peptone (Witte's) intravenously. To attain 

 the aforesaid result, it is sufficient as a rule to use about 0.3 gram of 

 peptone per kilo of the body weight. The blood of a peptonized 

 animal remains fluid for hours after its withdrawal, and non-coagulable 

 plasma may be obtained from it by the use of the centrifuge. Pep- 

 tone solutions, however, are quite unable to produce this effect if the 

 animal has been fed shortly before the injection or if they are added 

 to fresh normal blood after it has been withdrawn from the body. 

 It has also been noted that they do not retard the clotting very ap- 

 preciably when introduced into the peritoneal cavity instead of directly 

 into the blood-stream. This method of rendering the blood non- 

 coagulable cannot be recommended for experiments upon the circula- 



1 Intern. Beitrage fur Virchow's Festschrift, i, 1891. 



2 Zeitschr. fur phys. Chemie, xxii, 1896, 333. 



