214 THE BLOOD 



dependent upon the work of Wooldridge and others, has recently been 

 advocated by Nolf ^ and Howell.^ It is held that prothrombin may be 

 changed into thrombin by means of calcium alone, but this reaction 

 is prevented ordinarily by an antithrombin^ which is always present 

 in the blood. If the blood is injured, a thromboplastic substance is 

 liberated by the corpuscles (platelets), which neutralizes the action of 

 the antithrombin and allows the activation of the prothrombin by the 

 calcium. The second stage of coagulation takes place as described 

 previously. The theories just outlined, therefore, differ only in 

 regard to the action of the '' kinase" which, on the one hand, is said to 

 act as a ferment which actually takes part in the activation of the pro- 

 thrombin, and, on the other, is believed to inhibit the anticoagulating 

 substance so that the calcium is able to incite the reaction. 



Thrombokinase. — As it has not been possible so far to demonstrate an organic 

 kinase in the plasma of the blood, it is commonly held that this clotting agent is 

 contained in the formed elements. For this reason, a disintegration of the latter 

 must necessarily precede the liberation of this substance, but as relatively few red 

 cells are destroyed during the shedding of the blood, it may be concluded that 

 these elements cannot possibly harbor the coagulating agent. It has also been 

 observed that these cells are quite ineffective under ordinary conditions, but 

 may be changed into a coagulating agent if the hemoglobin is thoroughly separated 

 from the stroma. With the help of the latter even intravascular clotting can 

 readily be effected. Practically the same statement may be made regarding the 

 white corpuscles. It is true, however, that under experimental conditions clot- 

 ting may be greatly accelerated by the addition of leukocytic material. But this 

 fact cannot be employed as a strong argument in favor of the view that they do 

 play a part in normal clotting, because they are found in large numbers in exudates 

 in which coagulation has not taken place. And furthermore, plasma from which 

 the leukocytes and red cells have been removed by centrifugalization, may be made 

 to clot by the addition of water or by passing a current of carbon dioxid through it. 

 Wooldridge, moreover, has shown that the white cells of lymph, when washed in 

 salt solution, are quite unable to clot the lymph from which they have been taken 

 and neither can they coagulate peptone-plasma in the absence of platelets or their 

 derivatives. 



The thrombocytes, on the contrary, have been shown to exert a most important 

 influence upon coagulation, because they disintegrate very rapidly in shed blood 

 and the amount of fibrin formed is nearly proportional to the number of platelets 

 destroyed. Various experiments may be cited in support of this statement. 

 Thus, it is possible to increase or to decrease their destruction by subjecting them 

 to different temperatures or to different mechanical and chemical influences. 

 In general, it holds true that a medium which tends to preserve them, delays the 

 coagulation, while a medium which is injurious to them, hastens this process. 

 For example, if a drop of a solution of ammonium oxalate (1/100 N) is added to a 

 drop of blood, coagulation fails to take place. If this sample of blood is examined 

 later on, it will be found to contain the thrombocytes in a state of perfect preserva- 

 tion, while the red and white corpuscles are thoroughly fragmented. Moreover, 

 Schmidt has called attention to the fact that the plasma derived from sedimented 

 horse-blood, exhibits a difference in its coagulability in so far as its upper portion 

 clots more readily than its lower, but may be made to remain fluid for a much 

 longer time than the latter by passing it through a filter. In explanation of this 



* Archives intern, de physiol., ix, 1910, 407. 

 2 Am. Jour, of Physiol., xxix, 1911, 29. 

 ' Called hepatothrombin by Nolf . 



