THEORIES OF COAGULATION 123 



dust particles, loose sweepings, or linty shreds be added, the coagulation is 

 equally prompt and in a number of experiments was more rapid than with tis- 

 sue extract." "The bird's blood or plasma clots with practically the same 

 rapidity and firmness if dust particles are generously added. Bits of down 

 or feathers introduced bring about a speedy clotting. Surely there can be 

 no question of a 'kinase' in these instances." "The existence of 'kinase' 

 or 'coagulins' in the various tissues is improbable. Using carefully pre- 

 pared fibrinogen solutions, extracts of tissues, irrigated to remove every 

 trace of thrombin-containing blood, cause no clotting. When the addition 

 of such extracts produces coagulation in bloods of bird or reptile, similar 

 results can be secured by the addition of substances, such as dust, lint, 

 shreds, etc., which preclude the presence of definite coagulating agents. 

 These results render very probable the assumption that in such plasmas all 

 the factors of coagulation are in reality present, and the addition of tissue 

 extract or other foreign substance brings into the mixture nothing that can 

 be regarded as a coagulin or as a kinase." 



Howell has been studying the phenomena of coagulation for- a number of 

 years. On the basis of his work he makes a somewhat different interpreta- 

 tion of the facts on which the theory of Morawitz is founded. By Howell's 

 view, "Circulating blood contains normally all the necessary fibrin factors, 

 namely, fibrinogen, prothrombin, and calcium. These substances are pre- 

 vented from reacting, and the normal fluidity of the blood is maintained, by 

 the fact that antithrombin is also present, and this substance prevents the 

 calcium from activating the prothrombin to thrombin. In shed blood the 

 restraining effect of the antithrombin is neutralized by the action of a sub- 

 stance (thromboplastin) , furnished by the tissue elements. In the mammalia 

 the thromboplastin is derived, in the first place, from the elements of the 

 blood itself (blood platelets). In the lower vertebrates the supply of this 

 material, in normal clotting, comes from the external tissues." Howell's 

 thromboplastin and Morawitz' thrombokinase are probably one and the 

 same substance, it being an enzyme by Morawitz' view, a property denied 

 by Howell and by Rettger. 



Quite recently Howell has thrown light on the nature of his thromboplastic 

 substance. He finds that the lipoid, kephalin, present in many tissues of the 

 body possesses the power of neutralizing antithrombin and is comparable, in 

 relation to blood clotting, to the action of thromboplastin. Lecithin does not 

 possess this property. 



One may restate Morawitz' view in a word as follows: The coagulation of 

 the blood takes place because of the formation of fibrin from fibrinogen by 

 the action of thrombin. The fibrinogen is constantly present in the plasma. 

 The thrombin is formed by the interaction of three substances, prothrombin, 

 calcium, and thrombokinase. The prothrombin arises chiefly from the dis- 

 integration of the blood platelets and leucocytes when the blood leaves the 



