THE BLOOD. 259 



tion or the conversion of prothrombin into thrombin as was conclusively 

 shown by Arthus and Pages: For if it is precipitated by the addition of 

 oxalate of potassium, coagulation will not take place. At all times then, 

 there are present in the blood, prothrombin, a calcium salt and fibrinogen. 

 Given the two former factors, the question arises why do they not react to 

 form thrombin in the circulating blood, and why do they so react in shed 

 blood? The answer of Morawitz is, that prothrombin requires an activating 

 agent, a kinase which is wanting in circulating blood but is present in shed 

 blood. It is supposed to develop in the disintegration of the cell elements of 

 the blood, leukocytes and blood platelets, and perhaps from the cell elements 

 of the injured tissues as the blood flows over them. Shortly after its appear- 

 ance the kinase, with the aid of the calcium salt converts the prothrombin into 

 thrombin, after which it unites with fibrinogen to form fibrin. For this 

 reason the kinase has been termed thrombo-kinase. 



The answer of Howell to the foregoing question is somewhat different and 

 based on a long series of experiments recently published. From the results 

 of these experiments the answer given is that prothrombin is prevented from 

 reacting with the calcium salt to form thrombin in the circulating blood, by 

 reason of the presence and union with prothrombin of an agent termed 

 anti-thrombin. So long as this combination is not disturbed the blood 

 remains fluid. When blood is shed there is supposed to develop from the cell 

 elements of the blood, the leukocytes and blood platelets, and perhaps from 

 the cell elements of the injured tissues as well, a plastin, the specific action of 

 which is to combine with the anti-thrombin and thus set free the prothrombin. 

 This having been accomplished the calcium salt activates the prothrombin, 

 and converts it into thrombin, after which it combines with the fibrinogen. 

 For this reason the plastic agent has been termed thrombo-plastin. 



Intra-vascular Coagulation. So long as the relations of the blood 

 and the vascular apparatus remain physiologic, no coagulation occurs in the 

 vessels. The reasons assigned for this are: (i) the absence of thrombo- 

 kinase in sufficient amounts; (2) the presence of an anti-thrombin. On either 

 assumption the reaction between prothrombin and calcium with the forma- 

 tion of thrombin does not take place. If the vessels are injured as they are 

 when ligated or torn or in any way impaired, coagulation promptly takes 

 place with the subsequent occlusion of the vessel. As to whether the injured 

 tissues or the blood cells now generate an agent, thrombo-kinase, which 

 activates the prothrombin and calcium, or whether they generate an 

 agent thrombo-plastin, which neutralizes an anti-thrombin, is a subject of 

 discussion. 



Under pathologic conditions of the circulatory apparatus, especially of 

 the internal lining, intra- vascular coagulation frequently arises, though the 

 process cannot be considered as identical with extra-vascular coagulation. 

 Many pathologists assert that in its origin, mode of formation, and structure 

 the intra- vascular coagulum or thrombus is not a true coagulum as ordinarily 

 understood, but rather a conglutination of blood-plaques and leukocytes. 

 Whenever the integrity of the internal wall of the vessel is impaired by 

 disease or by the introduction of foreign bodies, there is primarily a deposition 

 and accumulation of blood-plaques at the injured area or on the foreign body 

 which constitutes to a large extent the mass of the thrombus which at once 



