CO AGVL AVION OF THE BLOOD 343 



of Peptones or Proteoses. When these are injected into the circulation, 

 in a very brief period the blood which is drawn from the vessels is 

 found to be incoagulable. The Peptone-plasma obtained from this 

 blood by centrifugalization may be induced to coagulate by the mere 

 addition of a suspension of leukocytes obtained from lymph, or by the 

 addition of calcium chloride in excess of the amount already present 

 in the blood, or by acidification with carbon dioxide or acetic acid. 

 Wooldridge has also drawn attention to the very interesting property 

 possessed by some proteins which are probably Phosphoglobulins, 

 namely that of inducing Intravascular Clotting if injected into the 

 circulation gradually or in small doses; while they render the blood 

 Incoagulable if they are injected more quickly or in larger doses. The 

 former effect Wooldridge designated the Positive Phase of the action 

 of the protein, the latter he termed the Negative Phase. It is an 

 especially remarkable fact that, according to Pickering, albino rabbits, 

 and the Norway hare when in its albino condition, are immune from these 

 effects. These various phenomena have not yet received any adequate 

 interpretation. 



Another agent which renders blood incoagulable is the extract of 

 leeches' heads, known as Hirudin. Certain Snake Venoms induce a like 

 effect. 



'The clotting of the blood is in the first instance due to the trans- 

 formation of a soluble protein, Fibrinogen, into an insoluble modifi- 

 cation, Fibrin. This was conclusively shown by the investigations of 

 A. Schmidt and of O. Hammarsten. If the plasma obtained from blood 

 be mixed with an equal volume of a saturated solution of Sodium Chlo- 

 ride a precipitate or coagulum of fibrinogen is produced which may be 

 washed repeatedly in half-saturated sodium chloride solution, redis- 

 solved in dilute sodium chloride, reprecipitated by half-saturation 

 with sodium chloride and again redissolved. This solution of fibrinogen 

 in from 1.0 to 1.5 per cent, sodium chloride will not clot, however long 

 it may be allowed to stand. In order to induce it to clot, another 

 substance must be added to it, to which the name Thrombin has been 

 applied. 



Thrombin may be obtained from freshly-formed fibrin. It is best 

 prepared from the strings of fibrin which are obtained by whipping 

 freshly-shed blood; these are washed in cold water with constant knead- 

 ing until all of the Hemoglobin has been removed. The fibrin is then 

 squeezed dry, minced with scissors, and then covered with an eight 

 per cent, sodium chloride solution, which does not dissolve the fibrin, 

 but extracts the thrombin which is associated with it. The mixture is 

 placed in a refrigerator for forty-eight hours, and then filtered through 

 cheesecloth. A few drops of the viscous -filtrate, added to ten c.c. 

 of the fibrinogen solution, cause immediate clotting, without the 

 addition of any calcium salt. On the other hand, thrombin solution 

 unmixed with fibrinogen will not clot, whether calcium salts be added 

 to it or not. 



