COAGULATION OF THE BLOOD 347 



activity of the original unheated fluid. Evidently the kephalin in 

 tissue-extracts is carried down with the protein coagulum, either 

 physically adherent to it or else chemically combined with it. 



According to Howell, the activation of prothrombin by kephalin 

 is due to the removal from the plasma of an inhibiting substance, 

 Antithrombin, which is present in varying amounts in the blood of dif- 

 ferent species of animals. The proof for the existence of this substance 

 is as follows: If thrombin in a quantity known to be sufficient to 

 rapidly coagulate a given amount of a solution of fibrinogen be pre- 

 viously incubated for about fifteen minutes at blood-temperature with a 

 small amount of fresh plasma or of plasma freed from fibrinogen by 

 heating to 54 C., the ability of the thrombin to coagulate the fibrino- 

 gen is found to have become very much impaired. If, however, the 

 plasma has been previously treated with kephalin, its power of inacti- 

 vating thrombin is lost or very much weakened. This may be illus- 

 trated by the following data, furnished by Howell. The following 

 mixtures were prepared: 



Mixture A. Fresh pigs' plasma + equal volume of water. 



Mixture B. Fresh pigs' plasma + equal volume of kephalin solution. 



The mixtures were allowed to stand for thirty minutes and then 

 heated to 54 C. to coagulate the fibrinogen. The filtrates were then 

 tested for their antithrombin-content as follows: 



Mixture A, 1 drop + Thrombin 5 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = Partial clot in 65 mins. 

 Mixture A, 1 drop + Thrombin 4 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = No clot in 2 hours. 

 Mixture A, 1 drop + Thrombin 3 drops Incubation of 15 mins. 



-j- Fibrinogen 10 drops = No clot in 2 hours. 

 Mixture A, 1 drop + Thrombin 2 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = No clot in 2 hours. 



II 



Mixture B, 1 drop + Thrombin 5 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = Clot in 5 to 10 mins. 

 Mixture B, 1 drop + Thrombin 4 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = Clot in 5 to 10 mins. 

 Mixture B, 1 drop -f Thrombin 2 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = Clot in 5 to 10 mins. 

 Mixture B, 1 drop + Thrombin 2 drops Incubation of 15 mins. 



+ Fibrinogen 10 drops = Clot in 10 to 15 mins. 



It will be seen that the inhibitive action of mixture A is totally 

 absent in mixture B, which has been incubated with kephalin. These 

 results have found important surgical applications, both for controlling 

 hemorrhages, for which purpose gauze soaked in an aqueous solution 

 (or emulsion) of kephalin is employed, and for the treatment of ab- 

 normal tendency to prolonged hemorrhage in cases of Hemophilia, 

 which Howell interprets as being due to an abnormal content of anti- 

 thrombin in the blood of the patients who exhibit it. 



Hemophilia is a hereditary condition, and is further peculiar in 



