218 THE BLOOD 



clotting may be incited by introducing a solid object directly into the 

 blood-stream, or by causing a trauma of the blood-vessel and surround- 

 ing tissue so that these will be changed into destructive agents. A 

 thin layer of fibrin is then deposited upon the injured area, more and 

 more material being gathered in gradually until a clot has been formed 

 which may occlude the entire lumen of the blood-vessel. When fully 

 formed, a clot of this kind is known as a thrombus. After the blood 

 current has played against this intravascular coagulum for some time, 

 pieces of it may be broken off and carried to distant parts of the cir- 

 culatory system, where they may obstruct the blood flow and give rise 

 to an anemia and functional uselessness of the tissues situated distally 

 to the block. A floating thrombus is known as an embolus.^ The 

 ultimate outcome of a condition of this kind depends upon the freedom 

 with which the tissues so cut off may be supplied with blood by anas- 

 tomosing vessels. It need scarcely be mentioned that the lining of 

 the blood-vessels may also be changed into a destructive agent by the 

 products of bacteria, and other toxic substances circulating through 

 the system. 



Intravascular clotting may also be incited experimentally by the 

 injection of solutions of various substances. In accordance with the 

 statements made previously, it might be supposed that thrombin or 

 thromboplastic substance would act as very powerful coagulating agents 

 when introduced into the circulation, but, curiously enough, the system 

 possesses the power of protecting itself against them. Howell believes 

 that the action of thrombin is neutralized in this case by a greater 

 production of antithrombin. 



The effects obtained with tissue extracts and solutions of thrombo- 

 plastic substance are rather perplexing. Extensive clotting most 

 frequently results in consequence of the injection of moderate amounts 

 of thrombokinase and extracts of organs rich in cellular elements, such 

 as the thymus and lymph glands. It has been suggested by Wool- 

 dridge that these extracts contain thrombokinase. Their injection, 

 therefore, leads to the same results as the liberation of this body in 

 shed blood. It is to be noted, however, that small quantities of these 

 extracts diminish the coagulability of the blood. The former reaction 

 is usually designated as the positive and the latter as the negative 

 phase of the injection, but as a lessening of the coagulability cannot be 

 obtained in this manner during extravascular clotting, it must find its 

 origin in certain functional pecuHarities of the tissue cells, analogous 

 to their behavior toward toxins. It is a well-known fact that the 

 injection of diphtheria toxin gives rise to a certain amount of antitoxin 

 in the course of two or three days. Additional injections, however, 

 most generally produce a complete disappearance of the antitoxin 

 until, a day or two later, it again makes its appearance in quantities 

 much larger than those present before the second injection. It should 



1 The circulation may also be obstructed by embolisms of different origin, for 

 example, by droplets of fat or bubbles of air. 



