262 TEXT-BOOK OF PHYSIOLOGY 



these changes take place in organic compounds the composition of which is 

 but imperfectly known, the intimate nature of the process is quite obscure. 

 All the theories which have been advanced in explanation, though approxi- 

 mating the truth, are more or less incomplete and in some respects contra- 

 dictory. Since the coagulation is coincident with the appearance of the 

 fibrin, the antecedents of this substance, the physical and chemic conditions 

 which condition its development, and the succession of chemic changes 

 involved must be determined, before any consistent theory can be established. 



Extra-vascular Coagulation. At present it is generally believed 

 that the immediate factors concerned in extra-vascular coagulation are 

 fibrinogen, a calcium salt, and an agent thrombin. As to the manner in 

 which these three bodies react one with another there is a diversity of opinion. 



As an outcome of a long series of experiments that have been performed 

 to determine the nature and the succession of the chemic phenomena 

 underlying the coagulation of the blood, the following facts seem to be well 

 established, viz: the immediate cause of the coagulation is the appearance 

 of fibrin, a derivative of an antecedent substance always present in the blood 

 termed fibrinogen; the cause of the conversion of the soluble fibrinogen into 

 the insoluble fibrin is the presence and activity, under the circumstances, of 

 an agent termed thrombin, the chemic nature of which is a subject of discus- 

 sion. By some chemists it is regarded as a ferment which causes a mo- 

 lecular rearrangement of the fibrinogen; by others it is regarded as a definite 

 organic colloidal body which unites in some physico-chemic manner with 

 the fibrinogen to form fibrin. 



The crux of the problem is the source and the conditions necessary for 

 the production of the thrombin. It is generally conceded that thrombin is a 

 derivative of an antecedent substance prothrombin or thrombogen, a substance 

 always present in the blood plasma, a product of the decomposition of blood- 

 platelets and leukocytes. With prothrombin there is physiologically associ- 

 ated a calcium salt, the presence of which is absolutely essential for coagula- 

 tion or the conversion of prothrombin into thrombin as was conclusively 

 shown by Arthus and Pages: For if it is precipitated by the addition of 

 oxalate of potassium, coagulation will not take place. At all times then, 

 there are present in the blood, prothrombin, a calcium salt and fibrinogen. 

 Given the two former factors, the question arises, why do they not react to 

 form thrombin in the circulating blood, and why do they so react in shed 

 blood? 



The answer of Morawitz is, that prothrombin requires an activating 

 agent, a kinase which is wanting in circulating blood but is present in shed 

 blood. It is supposed to develop in the disintegration of the cell elements of 

 the blood, leukocytes and blood-platelets, and perhaps from the cell elements 

 of the injured tissues as the blood flows over them. Shortly after its appear- 

 ance the kinase, with the aid of the calcium salt converts the prothrombin into 

 thrombin, after which it unites with fibrinogen to form fibrin. For this 

 reason the kinase has been termed thrombo-kinase. 



The answer of Howell to the foregoing question is somewhat different and 

 based on a long series of experiments recently published. From the results 

 of these experiments the answer given is that prothrombin is prevented from 

 reacting with the calcium salt to form thrombin in the circulating blood, by 

 reason of the presence and possible union with prothrombin of an agent 



