THE COAGITLATION OF THE BLOOD 215 



phenomenon, it may be stated that the thrombocytes, on account of their lesser 

 specific gravity, collect in much greater numbers near the surface of the plasma and 

 that they may then be removed from it by filtration. Bizzozero beat freshly 

 drawn blood with cotton threads until they were thoroughly covered with plate- 

 lets. They were then washed in a 0.7 per cent, solution of sodium chlorid to 

 remove the red corpuscles. If desired, a rapid coagulation of artificial pro- 

 thrombin could then be effected by suspending these threads in solutions of this 

 substance. To prove his point more conclusively, he showed subsequently that 

 this result cannot be obtained with the cotton threads alone, while threads covered 

 with red cells or with leukocytes, gave rise, at best, to only a very slow type of 

 coagulation. Moreover, it has been observed repeatedly that the disintegrating 

 thrombocytes act as centers for the formation of fibrin, and that the injection of 

 platelets into the circulation produces intravascular clotting. It must be con- 

 cluded, therefore, that the platelets yield a substance which serves as the exciting 

 agent of the coagulation. 



Morawitz calls this agent thrombokinase, but it is also referred to as cytocym. 

 If it is assumed that the platelets are not real cells but merely fluid crystals, the 

 liberation of the thrombokinase would correspond to the deposition of these 

 crystals as insoluble threads of fibrin. For the present, however, it seems best to 

 adhere to the view of Morawitz, Fuld and Spiro as previously outlined. In 

 accordance with this explanation, it becomes necessary to assume further that the 

 blood of those animals which does not clot when collected directly from the blood- 

 vessel, contains no thrombokinase. The absence of this agent is readily accounted 

 for, because these animals are not in possession of thrombocytes. Instead, 

 their tissues contain a very effective thromboplastic substance which takes the 

 place of thrombokinase and which is brought in contact with the blood as it 

 flows across the opened surface. But, the mere fact that 'in us and allied animals 

 the principal coagulating agent is held in the blood itself, does not preclude the 

 possibility of a similar substance being present in our tissues; in fact, it seems 

 entirely probable that we are thus doubly protected. 



Thrombogen is a normal constituent of the plasma. Only a part of it is used 

 up during coagulation. The remaining portion escapes activation either because a 

 sufficient quantity of thromboplastic material to cause its complete conversion is 

 not at hand, or because its formation is stopped as soon as the coagulation has 

 advanced to a certain stage. It is not present in the tissues, and the indications 

 are that it is not derived from the cellular elements of the blood, but is held in 

 solution in the plasma. Drinker^ believes that it arises in the bone-marrow, 

 because it may be removed from the latter in considerable amounts by perfusion. 

 It is very stable and is capable of withstanding the temperature of boiling water 

 for a brief period of time. Although calcium is necessary to incite its conversion 

 into thrombin, this salt is by no means the precursor of thrombin. Thrombogen 

 is also known as prothrombin, proferment or plasmozym. 



Thrombin, or fibrin ferment is not a preexisting constituent of the blood nor 

 of any one of the fluids of the body. Thus, if blood is withdrawn directly into an 

 excess of alcohol, the precipitate, when dried, pulverized, and extracted with 

 water, yields practically no thrombin. While it is usually regarded (Schmidt) 

 as an enzyme or ferment, it must be remembered that an agent of this kind possesses 

 the property of producing maximal reactions even when present in minute 

 amounts. Another peculiarity of enzymes is their power of producing a chemical 

 reaction without losing any of their substance. But as Wooldridge, Nolf and Rett- 

 ger2 have failed to observe these peculiarities in thrombin, its ferment nature has 

 not been definitely established. Indeed, the evidence seems to point rather the 

 other way, because it has been found that the amount of thrombin is directly pro- 

 portional to the amount of fibrin formed, as the following compilation will show : 



1 Am. Jour, of Physiol., xli, 1916, 5. 



2 Am. Jour, of Physiology, xxiv, 1909, 429. 



