468 BLOOD AND LYMPH. 



it follows that in all probability the neutral salts exert a restraining 

 effect on the process of clotting because they prevent or retard the 

 activation of the prothrombin by the calcium. 



4. By the Action of Oxalate Solutions. If blood as it flows from 

 the vessels is mixed with solutions of potassium or sodium oxalate 

 in proportion sufficient to make a total strength of 0.1 per cent, 

 or more of these salts, coagulation is prevented entirely. Addi- 

 tion of an excess of water does not produce clotting in this case, 

 but solutions of any soluble calcium salt quickly start the process. 

 The explanation of the action of the oxalate solutions is simple; 

 they are supposed to precipitate the calcium as insoluble calcium 

 oxalate. 



5. By the Action of Sodium Fluorid and Sodium Citrate. Blood 

 drawn directly into a solution of sodium fluorid does not clot. It is 

 best to use a 3 per cent, solution of the fluorid, and to take 1 part 

 of the solution to 9 parts of blood. Addition of thrombin to this 

 fluorid blood causes clotting, while calcium salts are usually stated 

 to be without effect. As a matter of fact, calcium salts cause a 

 precipitate of a portion of the protein, but if added cautiously in 

 excess they induce clotting, as in the case of the oxalated blood. 

 The fluorid plasma may be made to clot also by dialysis. We 

 may believe that the fluorid, like the oxalate, prevents clotting 

 by removing the calcium. The calcium is not precipitated, but is 

 held bound as a fluorid in combination with a portion of the 

 protein (Rettger). Coagulation is prevented in a similar way by 

 solutions of sodium citrate. In the case of the citrate one uses a 2 

 per cent, solution and takes 1 part to 4 of the blood. As in the case 

 of the fluorid, the citrate solutions do not cause an actual precipitate 

 of calcium. One explanation given for their efficiency in prevent- 

 ing clotting is that the calcium salt formed has a very small dis- 

 sociation constant, .so that the concentration of calcium ions is 

 reduced below the minimum necessary to activate prothrombin to 

 thrombin.* 



6. By the Injection of Certain Organic Substances. There are a 

 number of substances which when injected into the blood retard 

 or prevent its coagulation. For instance, solutions of ordinary 

 preparations of pepsin, trypsin, peptone, snake venom, leech 

 extracts, etc. Snake venom may be wonderfully potent in this 

 particular; it is stated that so little as 0.00001 gm. to each kilogram 

 of animal suffices, to destroy the coagulability of the blood. Of 

 these various bodies solutions of peptone have received the most 

 attention from investigators. Peptone, as usually obtained by 

 digestion experiments, is in reality a mixture of proposes and 

 peptones. When injected into the circulation in the proportion of 



* Sabbatani, "Archives ital. de Biologie," 39, 333, 1903. 



