464 BLOOD AND LYMPH. 



tralize the antithrombin. If the shed blood comes into contact 

 with the tissues, additional thromboplastic material is added which 

 accelerates the process of thrombin formation. From this point 

 of view, therefore, antithrombin plays the important role of pro- 

 tecting the blood from clotting within the vessels. Observations 

 on human blood under normal and pathological conditions show 

 that this substance is constantly present, and in amounts that 

 seem to vary within narrow limits. Regarding the seat of forma- 

 tion of the antithrombin, Delezenne, Nolf, and others have pub- 

 lished experiments which indicate that it is formed in the liver, 

 and there is evidence that it is produced normally in the uterus 

 at the time of menstruation.* 



Metathrombin. In the serum of blood after clotting ready- 

 formed thrombin exists. On standing the amount of this thrombin 

 diminishes sometimes quite rapidly, so that after a certain time the 

 serum shows little or no power to cause the clotting of a fibrinogen 

 solution. In either a fresh or an old serum, if not kept too long, 

 the thrombic power can be very greatly increased if it is treated 

 with an equal volume of a decinormal solution of sodium hy- 

 droxid for a few minutes and then neutralized with acid (Fuld and 

 Spiro and Morawitz). The same result may be obtained with 

 fresh serum by adding a little tissue extract, or a solution of the 

 active substance in such extracts (kephalin) . It has been suggested, 

 therefore, that at the time of clotting a portion of the prothrombin 

 in the blood-plasma is converted into an inactive form known as 

 metathrombin, which may be activated to thrombin by either of the 

 methods mentioned above. A simpler explanation is that this 

 so-called metathrombin represents a combination of thrombin and 

 antithrombin, from which the thrombin is liberated either by the 

 alkali activation or in the case of fresh serum by the action of 

 kephalin. f 



Intravascular Clotting. As is well known, clots may form 

 within the blood-vessels in consequence of the introduction of for- 

 eign material of any kind. Air, for instance, that has gotten into 

 the veins, if not absorbed, may act as a foreign substance and 

 cause the same chain of events as when the blood is shed, namely, 

 the disintegration of formed elements, formation of thrombin, and 

 clotting. So also when the internal coat of a blood-vessel is in- 

 jured, as, for instance, by a ligature, the altered endothelial cells 

 act as a foreign substance. If the circulatory conditions are favor- 

 able for instance, if the ligated artery causes a stasis of blood at 



* See Doyon, "C. r. de la soc. de Biologic," 1911-1912; Schickele, "Bio- 

 chemische Zeitschrift," 38, 169, 1912; also Howell, "American Journal of 

 Physiology," 29, 187, 1911. 



t Weymouth, "American Journal of Physiology," 32, 266, 1913, 



