H. E Smith 



551 



2N molecules continuously present represent the average thrombin "popula- 

 tion." Since a stable population is the product of life span by number of 

 births, it follows that the average life span of each thrombin molecule is 

 approximately 2/5 minutes, or 24 seconds, if one asstimes the "birth" and the 

 "death" of each molecule to be instantaneous. It is during this brief 24-second 

 period that the thrombin molecule is available for reaction with any fibrinogen 

 which may be present. It is the astonishing activity of antithrombin which 

 makes necessary the enormous excess of prothrombin which is required to 

 build up a "thrombin tide" quickly and to adequate levels for clot formation. 



TABLE 2 



Prothrombin and Thrombin Titers in Serum Allowed to "Age" 



AFTER Removal of the Blood Cells by Centrifugalization 



Tube number 



I 



2 



3 



4 



5 

 6 



7 



Age of serum* 



2omin. 



30 min. 



41; min. 



' ihr. 



2 hr. 



4 hr. 



7 hr. 



Prothrombin titer, 

 units 



225 

 200 

 170 

 150 



93 

 60 



Thrombin titer, 

 units 



1-5 

 0.8 



0.4 



o. 2 



0.0+ 



0.0+ 



* Whole blood placed in test tube, allowed to stand ten minutes at room temperature, 

 then centrifugalized for ten minutes at s'^ C. The serum was removed and its "age" dated 

 from the time the blood was drawn. 



By the same token, it is the obvious role of the antithrombin to protect the 

 circulation against the baneful effects of the enormous excess of thrombin 

 which might spread from areas of thrombosis to endanger the fluidity of the 

 entire mass of circulating blood. 



The Effect of Cellular Elements on the "Thrombin Tide." The thrombo- 

 plastin which is needed for clotting is derived from margins of wounds, from 

 injury of fixed tissues, and from disintegration of blood cells and platelets. 

 In the experiments reported in table 1, it is almost certain that most of the 

 thromboplastin came from blood cells and platelets; it is unlikely that much 

 came from the margins of the venipuncture wound. It will be noted that in 

 these experiments the cells and platelets were continuously present throughout 

 the entire period of the experiment. The continued disintegration of these cells 

 and platelets may provide more and more thromboplastin as long as the blood 

 is allowed to stand. If this w^ere so one would expect that prothrombin woidd 

 be converted to thrombin more slowly if the cells were removed by centrifugali- 

 zation soon after the blood was drawn. To test this point, w^hole blood was 

 allowed to stand for ten minutes only, after which it was centrifugalized for 

 ten minutes, during which time it clotted. The serum was carefully removed 

 and was allowed to stand at room temperature. The initial assays on this 



