THE COAGULATION OF BLOOD 

 QUANTITATIVE VIEWPOINTS* 



IT IS ONLY in recent years that quantitative viewpoints have gained a promi- 

 nent place in the literature of blood coagulation. Methods for the assay of 

 fibrinogen and fibrin are well established/ and quite recently methods have 

 been devised for the assay of prothrombin and thrombin/"* The thrombin 

 unit has been defined""* as the amount of activity which will cause coagulation 

 of 1 cc. of standard fibrinogen solution in 15 seconds. One unit of prothrombin 

 is the amount which, on maximal conversion, is capable of forming one unit 

 of thrombin. 



In normal clotting, the rate at which thrombin forms depends upon the 

 amounts of prothrombin and thromboplastin present in the clotting mixture. 

 Inhibitors likewise affect conversion rate. Recent work""" indicates that the 

 rate may also be determined by a "convertibility factor" of unknown nature. 

 To add to the complexity, it is known that the thrombin, once formed, is 

 rapidly destroyed by antithrombin. This complex interplay of variables is 

 indeed bewildering, for our concepts are purely at the qualitative level. To 

 comprehend the process as a whole, it is now quite evident that the quanti- 

 tative concept must be developed. Only then can we truly understand the 

 interplay of variables and the significance of clotting time and the reasons 

 for variations in the latter. 



Assay methods for thromboplastin, inhibitors, and the "convertibility fac- 

 tor" are still incompletely developed, and a complete quantitative analysis 

 of the clotting problem is not at present possible. It is proposed, nevertheless, 

 to make a beginning by presenting certain quantitative data regarding pro- 

 thrombin and thrombin titers. These data will help to outline the problem 

 and to indicate the nature of the problems which still await solution. 



The Period of Inductio7i in Blood Clotting. This expression was introduced 

 by Mills'" to designate the period which must elapse before thrombin can be 

 formed in sufficient amounts to cause clotting— a period which is normally 

 4-8 minutes. Mills believed that almost the entire period is consumed in re- 

 actions preparatory to thrombin formation, and that thrombin does not make 

 its first appearance until a few seconds before the clot forms. From a theoretical 

 standpoint it is, nevertheless, possible that traces of thrombin do appear 

 earlier, but are kept minimal through action of antithrombin. This possibility 

 must be kept in mind in connection with the oft-reported statement that the 

 early stages of clotting, taken as a whole, are autocatalytic in nature (see 

 Astrup^). The writer has employed the new assay techniques in an effort to 

 determine whether small amounts of prothrombin do disappear during the 



* .^ided by a grant from the John and Mary R. ^^arkle Foundation. 



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