COAGULATION. 465 



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). When this same method of alkali-acid 

 treatment is applied to plasma (oxalated plasma) no yield of throm- 

 bin is obtained. It is evident from these facts that serum contains 

 a source of thrombin other than prothrombin, which does not exist 

 in plasma. Morawitz designated this form of inactive thrombin as 

 metathrombin. Several observers* in this country have given rea- 

 sons for believing that metathrombin is a compound of thrombin 

 and antithrombin. It is known that serum has a large capacity 

 for inactivating thrombin. When the latter is added to serum it 

 soon disappears, and the suggestion made is that it combines with 

 antithrombin to form metathrombin. On this view it would seem 

 that in fresh serum there is present some active thrombin left over 

 from the coagulation, and two forms of inactive thrombin; namely, 

 some prothrombin not converted to thrombin in the act of clotting, 

 and some metathrombin formed after the act of clotting by a union 

 of free thrombin and antithrombin. The prothrombin of serum 

 may be converted to thrombin by adding cephalin or tissue-extract, 

 but to liberate thrombin from metathrombin requires the stronger 

 alkali-acid treatment described above. It has been suggested 

 (Gasser) that the formation of metathrombin constitutes normally 

 a safety device to prevent intra vascular clotting; that is to say, if 

 thrombin is formed in small quantities in the circulating blood it 

 may be seized and inactivated by the antithrombin. Under the 

 conditions of shed blood when there is a more massive production of 

 thrombin this protection is inadequate. Clotting takes place, but 

 the excess of thrombin left over is soon inactivated by conversion 

 to metathrombin. 



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 



*Weymouth, "American Journal of Physiology," 32, 266, 1913; Gasser, 

 ibid., 42, 378, 1917; and Rich, ibid., 43, 549, 1917. 



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