416 BLOOD AND LYMPH. 



60 C, a temperature sufficient to precipitate the fibrinogen as a 

 heat coagulum, its power of clotting is lost. Clotting, therefore, is 

 essentially a process of the blood-plasma, as was shown indeed by 

 the old experimenters (Hewson). Moreover it is also admitted that 

 the conversion of the soluble fibrinogen to the insoluble fibrin is 

 accomplished by the agency of an unorganized ferment or enzyme, 

 which is not present, in its active form at least, in the blood while in 

 the blood-vessels, but is formed after the blood is shed or under 

 certain abnormal conditions within the blood-vessels. These two 

 important facts in the definite form in which they are stated 

 we owe mainly to the investigations of Alexander Schmidt,* whose 

 work completed the older observations of Hewson, Buchanan, 

 Denis, and Brucke. 



Fibrinogen is readily prepared by the method of Hammarsten 

 from the plasma of horses' blood that has been kept from clotting 

 by cooling. By several successive precipitations with sodium 

 chlorid it can be obtained free from the other proteids of blood, and 

 upon the addition of a solution of fibrin ferment it gives a typical 

 clot. Fibrin ferment solutions are prepared by the method first 

 suggested by Schmidt. Blood-serum is precipitated by the addi- 

 tion of fifteen to twenty times its volume of alcohol, and the precipi- 

 tate is allowed to stand under the alcohol for at least fourteen days 

 in order to render the proteids insoluble. The precipitate is then 

 dried over sulphuric acid and extracted with water. The aqueous 

 solutions thus obtained cause solutions of fibrinogen to clot, and 

 induce coagulation in certain pathological exudates, such as 

 hydrocele liquid, which contain fibrinogen, but are not spontane- 

 ously coagulable. The fibrin ferment solutions are destroyed by 

 moderate heat, 50 to 60 C. As is seen from the method of prep- 

 aration, the ferment is contained in fresh blood-serum. Schmidt 

 was able to show, however, that it is not present, in detectible 

 amounts at least, in normal blood. That is, if blood flowing im- 

 mediately from an artery is caught under alcohol and is treated as 

 described above for the serum it yields no ferment. The conclu- 

 sion, therefore, is justified that the active ferment is formed after 

 the blood is shed. Schmidt subsequently designated this ferment 

 as thrombin. A third fact of essential importance in theories of coag- 

 ulation is that soluble calcium salts are necessary to the process. 

 This discovery was made definitively by Arthus and Pages,f who 

 showed that blood received into an oxalate solution, so as to 



* "Archiv f. Anat., Physiologie, u. Wiss. Medicin," Reichert u. du Bois- 

 Reymond, 1861, pp. 545, 675, and 1862, pp. 428, 533; "Pfliiger's Archiv f. 

 d.gesammte Physiol.," 6, 413, 1872; "Zur Blutlehre," Leipzig, 1892 and 1895. 



f "Archives de physiologie normale et pathologique, fifth series, 2, 739, 

 1890. 



