BLOOD CLOTTING 111 



may cause at first a prolongation and later a shortening of the time. 

 These results with larger doses are related to Howell's observation that 

 repeated doses of relatively large amounts of epinephrine in dogs may 

 so greatly retard coagulation as to make the animals practically hemo- 

 philic. It was further found by Cannon and his coworkers that epineph- 

 rine does not influence the clotting time when injected into animals 

 from which the abdominal viscera have been removed from the circulation 

 by ligation of the inferior vena cava and the abdominal aorta. In the light 

 of the influence which destruction of liver cells (by phosphorus, chloro- 

 form, etc.) is known to have in lengthening clotting time, it would seem 

 reasonable to conclude that it must be through this organ that epineph- 

 rine develops its clotting effects. 



Stimulation of the splanchnic nerves also shortens the clotting time, 

 and it would appear that this action depends on the resulting hyperse- 

 cretion of epinephrine (page 746), for it is not observed following stimula- 

 tion of the nerves in animals from which the adrenal glands have been 

 excised (Cannon and Mendenhall). The interesting suggestion is made 

 by Cannon that the shorter clotting time observed in animals showing 

 strong emotions of fright or fear may also be due to the hypersecretion 

 of epinephrine which this worker believes accompanies such states. 



Blood Clotting in Disease 



With the factors concerned in the process so wrapped in mystery, it is 

 not surprising that the underlying causes responsible for delayed or de- 

 ficient clotting of blood in diseased conditions or for the formation of 

 intravascular clots (thrombi) are little understood. According to How- 

 ell's theory of the nature of the process, which is the most satisfactory at 

 the present time, abnormal clotting might be due to the following 

 causes: (1) A diminished amount of fibrinogen. This occurs when the 

 hepatic cells are greatly damaged, as in poisoning by chloroform or 

 phosphorus and in such diseases as acute yellow atrophy and yellow 

 fever. In many cases of chronic cirrhosis of the liver, as Whipple, etc., 15 

 have shown, the blood also clots feebly because of deficient fibrinogen. 

 It should be pointed out that it is not so much the clotting time that is 

 increased in such cases, as -the firmness or consistency of the clot that 

 is affected. 



2. A deficiency in prothrombin. In the condition known as "melena 

 neonatorum," undoubted benefit is derived from intravenous injections 

 of blood serum or by direct blood transfusions, probably because throm- 

 bin or prothrombin is thus furnished. 



3. A deficiency of thromboplastin. Since this substance is derived from 

 both blood cells and tissue cells, it does not seem likely that a deficiency 



