316 DISTURBAyCEl^ OF CIRCULATION 



Theories of Fibrin Formation. — The great problem is the nature and the place 

 and manner of uriuin of the librin-forming enzyme, generally called fihrin-ferment 

 (also ])lasmasc. thrombin and coa<iuUn). Tlie most fimdamental theory of the 

 origin and nature of fil)rin-fernient is that of Alexander Schmidt, which may be 

 briefly described as follows: The ferment, Schmidt believes, exists in the plasma 

 in an inactive (prozyme or zymogen) form, which he calls prothrombin. Upon 

 disintegration of the leucocytes there is set free a substance, which, acting upon 

 the prothrombin, converts it into the active thrombin; this activating agent 

 Schmidt designates as the zymoplasiic substance. With various modifications 

 this stands to the present day as a basic theory. 



It having been sliown that calcium facilitates the formation of fibrin, Pekel- 

 haring advanced tlie idea that the protliruinl)iii does not exist in the plasma, but 

 is liberated from the leucocytes, and, coml)ining with the calcium of the plasma, 

 forms the thrombin. Morawitz considers three substances necessary for tlie forma- 

 tion of thromliin. (1) the prothrombin or thrombogen, which he believes orig- 

 inates in the blood-plates; (2) the zymoplastic substance or thrombokinase, which 

 is liberated from the leucocytes into the plasma: (3) calcium salts. Howell, 20 

 however, explains coagulation as follows: Circulating blood normally contains 

 all the necessary factors for fibrin formation, i. e., fibrinogen, prothrombin and 

 calcium. But there is also present an inhiliiting substance, antithrombin, which 

 j)revents the calcium from activating the protliromljin into thromliin. In shed 

 blood there appears a thromboplastin, derived from the platelets or the tissues, 

 wliich neutralizes the antithrombin and thus permits thrombin to form. Rett- 

 ger 22 holds that the coagulation of the blood is not a true enzyme action at all, 

 while Bordet and Delange 23 consider that thrombin is formed by the interaction 

 of cytozyme from the platelets or tissue cells, and serozyme of the plasma. 

 Mathews follows Wooldridge and considers the clotting of the blood as essentially 

 the crystallization of a phospholipin-protein compound, blood plasma, the stability 

 of which compound is easily upset in many ways. The fibrin threads are essen- 

 tially liquid crystals coming out of a saturated solution, tlie blood plasma, which 

 is practically a dilute protoplasm. It will not serve our purpose, however, to go 

 further into the hypotheses and disputes over these questions, which are detailed 

 more fully in the literature previovisly cited, but it may be stated tJiat numero\is 

 American observers have found Howell's theory to fit well Avith both experimen- 

 tal and clinical observations on the variations in the coagulability of the blood. 



The question has been raised as to whether the leucocytes or platelets secrete 

 their fibrin-forming constituent (be it thrombokinase or prothrombin is a matter 

 of minor importance to the pathologist) or liberate it only after their disin- 

 tegration. So far as jiathological processes go, the latter seems to be the case, 

 the disintegration apparently occurring whenever the leucocytes come in contact 

 with a foreign body or witli dead and injiu'ed tissues. Tlie stroma of red cor- 

 puscles also contains tlirombokinase.^i Of the substances that may be isolated 

 from tissues, eephalin is found especially active in producing thrombosis, and 

 may be related to or identical with the thrombo]ilastin.2-'J 



Tissue Coag'ulins. — Among the other points that are of importance in patho- 

 logical conditions is the fact that not only the leucocytes, but also tissue-cells, 

 can liberate fibrin-forming substances (coaguUns is the non-committal term ap- 

 plied by Loeb). Howell considers that the eflfect of the tissue "coa'j;ulins" is 

 merely to neutralize tlie antithromliin of the blood, if such coagulins actually 

 exist; possilily tliere is tliromlio])histin in the tissues. These coagulating agents 

 are present in tissue extracts and are liberated whenever the tissues are injured; 

 muscle is rich in coagulin, as are also tlie liver and kidney, and. wliich is par- 

 ticularly important, the blood-vessel wall (L. Loeb). Pieces of these tissues 

 placed in contact with fibrinogen solution will bring about prompt clotting. An- 

 other important fact is that the coagulins, whetlier derived from leucocytes or 

 from the tissues, have a cci-tain degree of specificity — that is, they act solely or 



20Amer. .Tour. Phvsiol.. 1911 (20), 187. 

 22Amer. Jour. Pliysiol., 100!) (24), 40(i. 



23 Ann. Inst. Pasteur.. 1912 (20), (ioT. See also Lee and \'iiicent. Arch. Int. 

 Med., 1914 (1:5). 3!).S. 



24 Barratt, .Tour. Path, and Bact., 191.3 (17), 30:{. 



2.'-. Howell, Aiiicr, .[(.ur. I'livsiol., 1912 ( .'{l ) , 1, MacLean, ibid.. 191(1 (41), 2."')0. 



