544 LECTURE XXIII. 



Here nature has performed for us a physiological experiment. Evidently 

 some link in the chain of processes from those which start the coagulation, 

 to those that complete it, is missing. First it was suggested that perhaps 

 the calcium salts were not present. Direct experiment failed to confirm 

 this. The behavior cannot result from a deficiency in fibrinogen, for the 

 blood is found to yield just as much fibrin as normally. The remarkable 

 thing is the time that it takes for the blood to clot. If a trace of defibrin- 

 ated normal blood is added to the hemophilic blood, the coagulating is 

 thereby accelerated. 



It is evident that this abnormal blood contains all of the constituents 

 that are required for forming the clot. It contains sufficient fibrinogen, 

 sufficient calcium salts, and, as far as we are able to find out, enough of the 

 zymogen which antecedes the fibrin-ferment; but, on the other hand, one 

 obtains the impression that an insufficient amount of the agent is present, 

 which changes the zymogen of the fibrin-ferment into the active state. We 

 have designated this substance as a kinase, and suggested that it occupies 

 a similar position to that of enterokinase. Now cases of hemophilia have 

 been known in which all of the blood did not show this abnormal behavior, 

 but in which it was restricted to the blood from certain parts of the body, 

 especially from the blood-vessels in the mucous membrane. While injuries 

 to the skin, for example, caused a normal bleeding, a very slight injury 

 to the mucous membrane might cause enormous hemorrhages which could 

 hardly be checked at all. Now there is no doubt that there is some ana- 

 tomical anomaly in the walls of the blood-vessels concerned, for mere 

 scratches which would not ordinarily cause any bleeding at all, now cause 

 it to take place profusely. But while it is easy to understand that abnor- 

 mally constructed blood-vessels may be injured more readily, this does not 

 explain at all why it is that the blood from them does not coagulate. 



The characteristic phenomenon with such bleeding is that the blood 

 constantly oozes through a loose clot exactly as through a sponge. The 

 coagulum formed is not connected properly with walls of the injured 

 blood-vessels. At the best, it is merely suspended from walls without 

 being closely bound to them. It does not fulfill its normal function of 

 checking the flow of blood. This tends to lead one to suspect that the walls 

 of the blood-vessels themselves have something to do with the clotting of 

 the blood, and most probably in the sense that the injured cells give up 

 something which accelerates the coagulation process. We must designate 

 this substance as a kinase, and localize its function in the entire process to 

 that of the preliminary stage; i.e., we must ascribe to it the property of 

 activating the zymogen of the fibrin-ferment. Consequently a chemical 

 anomaly is closely connected with this anatomical one. It is not impossible 

 that further studies based upon these observations will eventually show 

 what parts of the walls of the vessels take part in the secretion of the kinase. 



