308 THE BLOOD 



the blood decreases markedly, i.e. the concentration and mobility 

 of ions has been reduced. From a study of the form of the 

 curves produced by plotting the rate of diminution of electrical 

 conductivity against time, and the rate of fibrin formation against 

 time, etc., one arrives at two conclusions, viz. {a) that the process 

 is auto-catalytic {q.v.) and is in two stages ; and {h) that calcium 

 is necessary only in one of these stages, i.e. in the liberation of 

 thrombin from its precursor. 



Stewart and Percival have carefully examined the part played 

 by calcium in the coagulation process. This metal exists in the 

 blood in three forms, viz. ionic, molecular and colloidal. The 

 last is non-dialysible, while the two other forms readily pass 

 through a dialysing membrane. According to these investigators, 

 it is the non-diffusible calcium that is effective in the formation of 

 a clot. Ionic calcium seems definitely to inhibit the process. 



Certain substances by preventing the calcium from acting on 

 prothrombin prevent clotting. One of these, called heparin by 

 Howell, arises in the liver. Certain salts act on the calcium. For 

 example, oxalates, fluorides, etc., form insoluble calcium salts, and 

 when they are added in sufficient quantity they will cause the 

 precipitation of the major portion of the total calcium of the 

 blood. Citrates, on the other hand, reduce both the ionic and the 

 non-diffusible calcium, and if enough citrate is added, all the 

 calcium of the blood will be in the non-ionised but diffusible form. 

 The addition of a soluble calcium salt to oxalated or citrated blood 

 causes, in time, an increase in the non-diffusible calcium. When 

 this latter reaches a certain concentration coagulation occurs. 



(4) Platelets. The platelets (q.v.) have recently received renewed 

 attention as clot-formers. Bedson and others have noticed that 

 in whole blood, clotting seems to start at the platelets, i.e. they 

 may initiate the process. Further, when the platelets are excluded, 

 a clot may still be formed, but it does not undergo typical retrac- 

 tion and lacks firmness. If such a clot is plugging a wound it is 

 very easily dislodged. A good clot normally formed in the presence 

 of sufficient platelets would have a considerable tenacity, holding 

 firmly to the edges of the Avoimd and so knitting these edges 

 together, Bedson attributes to the platelets the production of 

 thrombokinase (cf. Tait, above). 



Most of the work mentioned above has been done in vitro ; 

 that is, blood has been collected into a vessel, or plasma has been 

 separated from the corpuscles by centrifuging, and allowed to clot 

 under observation. Such experiments may lead to quite a mis- 

 taken idea of the process as it occurs in vivo. When a blood 

 vessel is punctured and the blood allowed to flow to the surface 



