108 THE BLOOD AND THE LYMPH 



frequent injections of small amounts of the above material are made, 

 instead of intravascular clotting, a delay in the coagulation time is 

 likely to occur. Indeed, repeated injections of small amounts may en- 

 tirely remove the clotting power of the blood. The readiness with which 

 this so-called " negative phase" appears, seems to depend on the nutri- 

 tive condition of the animal at the time of injection. If a large dose is 

 injected into a fasting dog, for example, thrombosis is confined to the 

 portal area, whereas if it is injected into a recently fed animal, the 

 thrombosis is universal throughout the vascular system. The develop- 

 ment of the negative phase is undoubtedly dependent upon some reac- 

 tion on the part of the living cells of the organism, since it does not occur 

 on the addition of similar substances to blood outside the body. The 

 reaction is, indeed, akin to that by which immune bodies in general are 

 produced. For example, a toxin injected in large amount has a cer- 

 tain toxic effect, but in repeated small doses with intervening intervals 

 it leads to the production of an antitoxin. So with the substance in 

 question; a large dose injected at one time causes a positive effect clot- 

 ting but smaller doses frequently injected, the opposite effect want of 

 clotting. It is probable, as suggested by Starling, that more intensive 

 study of the conditions causing intravascular clotting will throw con- 

 siderable light on the general question of the production of immunity. 



Measurement of the Clotting Time 



To measure the clotting time of drawn samples of ~blood, several con- 

 ditions must be observed. These have been tabulated by Addis 11 as 

 follows: 



1. The specimens of blood must always be obtained by exactly the 

 same technic. It would introduce serious errors to compare the clot- 

 ting time of one specimen of blood received from an incision of the 

 skin (ear lobe) with that of another collected in a syringe by veni- 

 puncture. 



2. The temperature conditions must always be the same. Probably 

 25 C. is the best temperature to use. Higher temperatures are unsuit- 

 able for two reasons: first, because during its collection the blood will 

 have become cooled to about or below this point, and time Avould be con- 

 sumed in raising it higher; and second, because the time of coagulation 

 is more and more shortened for each degree that the temperature is 

 raised, this acceleration becoming especially pronounced for tempera- 

 tures above 25 C. Quite apart from the liability to incur errors inci- 

 dent to measurement of shorter periods of time, observations at higher 

 temperatures necessitate most rigorous adherence to a fixed temperature 

 of the water-bath. Temperatures much below 25 C. are unsuitable, be- 



